Denise M Arrick

Louisiana State University Health Sciences Center Shreveport, Shreveport, Louisiana, United States

Are you Denise M Arrick?

Claim your profile

Publications (25)66.14 Total impact

  • Source
    C. Li · Z. Jiang · W. Lu · D. Arrick · K. McCarter · H. Sun
    [Show abstract] [Hide abstract]
    ABSTRACT: We determined the effect of obesity on early post-ischemic blood-brain barrier (BBB) disruption. Male C57BL/6J mice were fed a high-fat diet (HFD) or standard chow for 16 weeks. Transient focal cerebral Ischemia was induced by directly ligating the middle cerebral artery (MCA) for two hours. Early BBB disruption was assessed by measuring Evans Blue (EB) and sodium fluorescein (Na-F) extravasation at 3 hours of reperfusion. Obesity produced an increase in cerebral vasodilation/hyperemia during reperfusion. L-NPA and 7-NI (neuronal nitric oxide synthase (nNOS) inhibitors) failed to alter the cerebral vasodilation/hyperemia in lean mice, but significantly inhibited the cerebral vasodilation/hyperemia in obese mice. The magnitude of early post-ischemic BBB disruption was significantly greater in obese mice compared to lean mice. Topical treatment with L-NPA, 7-NI or L-NAME (a nonspecific nitric oxide synthase (NOS) inhibitor) completely abolished the BBB disruption in lean mice, but only partially suppressed the BBB disruption in obese mice. Furthermore, a reduced matrix metallopeptidase (MMP)-9 activity and increased endothelial NOS (eNOS) accompanied with unchanged protein expression of tight/adherens junctions were found in cerebral cortex of obese mice. Our findings suggest that obesity exacerbates early post-ischemic BBB disruption via a mechanism independent of MMP or NOS. This article is protected by copyright. All rights reserved.
    Preview · Article · Jan 2016
  • Chun Li · Hong Sun · Denise M. Arrick · William G. Mayhan
    [Show abstract] [Hide abstract]
    ABSTRACT: Tobacco smoking is a risk factor contributing to the development and progression of ischemic stroke. Among many chemicals in tobacco, nicotine may be a key contributor. We hypothesized that nicotine alters the balance between oxidant and antioxidant networks leading to an increase in brain injury following transient focal cerebral ischemia. Male Sprague-Dawley were treated with nicotine (2 or 4 mg/kg/day) for 4 weeks via an implanted subcutaneous osmotic minipump and subjected to a 2-hour middle cerebral artery occlusion (MCAO). Infarct size and neurological deficits were evaluated at 24 hours of reperfusion. Superoxide levels were determined by lucigenin-enhanced chemiluminescence. Expression of oxidant and antioxidant proteins was measured using Western Blot analysis. We found that chronic nicotine exposure significantly increased infarct size and worsened neurological deficits. In addition, nicotine significantly elevated superoxide levels of cerebral cortex under basal conditions. Transient focal cerebral ischemia produced an increase in superoxide levels of cerebral cortex in control group, but no further increase was found in the nicotine group. Furthermore, chronic nicotine exposure did not alter protein expression of NADPH oxidase, but significantly decreased MnSOD and UCP-2 in the cerebral cortex and cerebral arteries. Our findings suggest that nicotine-induced exacerbation in brain damage following transient focal cerebral ischemia may be related to a pre-existing oxidative stress via decreasing of MnSOD and UCP-2.
    No preview · Article · Dec 2015 · Journal of Applied Physiology
  • Source
    William G. Mayhan · Jasmine P. Scott · Denise M. Arrick
    [Show abstract] [Hide abstract]
    ABSTRACT: Type 1 diabetes mellitus (T1D) impairs endothelial nitric oxide synthase (eNOS)-dependent responses of cerebral arterioles. However, the influence of T1D on another critical aspect of endothelial cell function in the cerebral microcirculation, i.e., regulation of permeability of the blood–brain barrier (BBB), remains largely unknown. Our goal was to examine basal and agonist-induced changes in permeability of the BBB in nondiabetic and type 1 diabetic (streptozotocin; 50 mg/kg IP) rats. On the day of the experiment (2–3 months after streptozotocin), a craniotomy was made over the parietal cortex in nondiabetic and diabetic rats. We measured the permeability of the BBB (FITC-dextran-10K) under basal conditions and during application of histamine. We also measured diameter of cerebral arterioles in response to histamine in the absence and presence of NG-monomethyl-L-arginine (L-NMMA). We found that basal permeability of the BBB was elevated in T1D and application of histamine did not produce a further increase in permeability. In contrast, basal permeability of the BBB was minimal in nondiabetics and histamine produced an increase in permeability. In addition, histamine-induced arteriolar dilation was less in diabetics than in nondiabetics, and vasodilation to histamine was inhibited by L-NMMA. Our findings suggest that T1D-induced endothelial dysfunction leads to an increase in basal permeability of the BBB, but decreases the ability of the endothelium of the BBB to respond to an important inflammatory mediator. Thus, T1D impairs two critical aspects of endothelial cell function in the cerebral microcirculation, i.e., basal and agonist-induced changes in permeability of the BBB and arteriolar dilation.
    Full-text · Article · Dec 2015
  • Source
    Zheng Jiang · Chun Li · Denise M Arrick · Shu Yang · Alexandra E Baluna · Hong Sun
    [Show abstract] [Hide abstract]
    ABSTRACT: The role of nitric oxide synthases (NOSs) in early blood-brain barrier (BBB) disruption was determined using a new mouse model of transient focal cerebral ischemia. Ischemia was induced by ligating the middle cerebral artery (MCA) at its M2 segment and reperfusion was induced by releasing the ligation. The diameter alteration of the MCA, arterial anastomoses and collateral arteries were imaged and measured in real time. BBB disruption was assessed by Evans Blue (EB) and sodium fluorescein (Na-F) extravasation at 3 hours of reperfusion. The reperfusion produced an extensive vasodilation and a sustained hyperemia. Although expression of NOSs was not altered at 3 hours of reperfusion, L-NAME (a non-specific NOS inhibitor) abolished reperfusion-induced vasodilation/hyperemia and significantly reduced EB and Na-F extravasation. L-NIO (an endothelial NOS (eNOS) inhibitor) significantly attenuated cerebral vasodilation but not BBB disruption, whereas L-NPA and 7-NI (neuronal NOS (nNOS) inhibitors) significantly reduced BBB disruption but not cerebral vasodilation. In contrast, aminoguanidine (AG) (an inducible NOS (iNOS) inhibitor) had less effect on either cerebral vasodilation or BBB disruption. On the other hand, papaverine (PV) not only increased the vasodilation/hyperemia but also significantly reduced BBB disruption. Combined treatment with L-NAME and PV preserved the vasodilation/hyperemia and significantly reduced BBB disruption. Our findings suggest that nNOS may play a major role in early BBB disruption following transient focal cerebral ischemia via a hyperemia-independent mechanism.
    Full-text · Article · Mar 2014 · PLoS ONE
  • Denise M Arrick · Shu Yang · Chun Li · Sergio Cananzi · William G Mayhan
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective: Our objective was to examine whether vigorous exercise training (VExT) could influence nitric oxide synthase (NOS)-dependent vasodilation and transient focal ischemia-induced brain injury. Rats were divided into sedentary (SED) or VExT groups. Materials and methods: Exercise was carried out 5 days/week for a period of 8-10 weeks. First, we measured responses of pial arterioles to an eNOS-dependent (ADP), an nNOS-dependent (NMDA) and a NOS-independent (nitroglycerin) agonist in SED and VExT rats. Second, we measured infarct volume in SED and VExT rats following middle cerebral artery occlusion (MCAO). Third, we measured superoxide levels in brain tissue of SED and VExT rats under basal and stimulated conditions. Results: We found that eNOS- and nNOS-dependent, but not NOS-independent vasodilation, was increased in VExT compared to SED rats, and this could be inhibited with L-NMMA in both groups. In addition, we found that VExT reduced infarct volume following MCAO when compared to SED rats. Further, superoxide levels were similar in brain tissue from SED and VExT rats under basal and stimulated conditions. Conclusions: We suggest that VExT potentiates NOS-dependent vascular reactivity and reduces infarct volume following MCAO via a mechanism that appears to be independent of oxidative stress, but presumably related to an increase in the contribution of nitric oxide.
    No preview · Article · Mar 2014 · Microcirculation (New York, N.Y.: 1994)
  • William G. Mayhan · Denise M. Arrick
    [Show abstract] [Hide abstract]
    ABSTRACT: Chronic hyperglycemia is associated with type 1 diabetes, and produces damage to many organ systems (including the brain), is a major cause of morbidity and mortality, and is a major economic burden throughout the world. Investigators have suggested that the damaging effects of diabetes on peripheral organs appear to be related to an increase in oxidative stress. Alterations in the reactivity of large and small arteries may contribute to the progression of organ damage observed in diabetics. The brain and the blood vessels within it are also susceptible to the damaging effects of hyperglycemia-induced increases in oxidative stress. Impaired dilation of cerebral vessels due to an increase in oxidative stress may contribute to the pathogenesis of diabetes-induced complications of the brain, including cognitive impairment and stroke. Many naturally occurring compounds are capable of ameliorating oxidative stress in blood vessels, thus producing an increase in overall vascular health. We will focus on the positive influence of resveratrol on cerebral arterioles in type 1 diabetes. We suggest an important therapeutic potential for resveratrol in treating diabetes-induced cerebrovascular dysfunction, including cognitive impairment and stroke.
    No preview · Article · Nov 2013
  • Denise M Arrick · Hong Sun · William G Mayhan
    [Show abstract] [Hide abstract]
    ABSTRACT: While exercise training (ExT) appears to influence cerebrovascular function during type 1 diabetes (T1D), it is not clear whether this beneficial effect extends to protecting the brain from ischemia-induced brain injury. Thus our goal was to examine whether modest ExT could influence transient focal ischemia-induced brain injury along with nitric oxide synthase (NOS)-dependent dilation of cerebral (pial) arterioles during T1D. Sprague-Dawley rats were divided into four groups: nondiabetic sedentary, nondiabetic ExT, diabetic (streptozotocin; 50 mg/kg ip) sedentary, and diabetic ExT. In the first series of studies, we measured infarct volume in all groups of rats following right MCA occlusion for 2 h, followed by 24 h of reperfusion. In a second series of studies, a craniotomy was performed over the parietal cortex, and we measured responses of pial arterioles to an endothelial NOS (eNOS)-dependent, a neuronal NOS (nNOS)-dependent, and a NOS-independent agonist in all groups of rats. We found that sedentary diabetic rats had significantly larger total, cortical, and subcortical infarct volumes following ischemia-reperfusion than sedentary nondiabetic, nondiabetic ExT, and diabetic ExT rats. Infarct volumes were similar in sedentary nondiabetic, ExT nondiabetic, and ExT diabetic rats. In contrast, ExT did not alter infarct size in nondiabetic compared with sedentary nondiabetic rats. In addition, ExT diabetic rats had impaired eNOS- and nNOS-dependent, but not NOS-independent, vasodilation that was restored by ExT. Thus ExT of T1D rats lessened ischemic brain injury following middle cerebral artery occlusion and restored impaired eNOS- and nNOS-dependent vascular function. Since the incidence of ischemic stroke is increased during T1D, we suggest that our finding are significant in that modest ExT may be a viable preventative therapeutic approach to lessen ischemia-induced brain injury that may occur in T1D subjects.
    No preview · Article · Aug 2012 · Journal of Applied Physiology
  • Source
    Hong Sun · Wanfen Xiong · Denise M Arrick · William G Mayhan
    [Show abstract] [Hide abstract]
    ABSTRACT: We examined the influence of low-dose alcohol consumption on cerebral ischemia/reperfusion (I/R) injury in mice and a potential mechanism underlying the neuroprotective effect of low-dose alcohol consumption. C57BL/6 J mice were fed a liquid diet without or with 1% alcohol for 8 weeks, orally treated with rosiglitazone (20 mg/kg/day), a peroxisome proliferator-activated receptor gamma (PPARγ)-selective agonist, or GW9662 (3 mg/kg/day), a selective PPARγ antagonist, for 2 weeks. The mice were subjected to unilateral middle cerebral artery occlusion (MCAO) for 90 minutes. Brain injury, DNA fragmentation and nuclear PPARγ protein/activity were evaluated at 24 hours of reperfusion. We found that the brain injury and DNA fragmentation were reduced in 1% alcohol-fed mice compared to nonalcohol-fed mice. Rosiglitazone suppressed the brain injury in nonalcohol-fed mice, but didn't alter the brain injury in alcohol-fed mice. In contrast, GW9662 worsened the brain injury in alcohol-fed mice, but didn't alter the brain injury in nonalcohol-fed mice. Nuclear PPARγ protein/activity at peri-infarct and the contralateral corresponding areas of the parietal cortex was greater in alcohol-fed mice compared to nonalcohol-fed mice. Using differentiated catecholaminergic (CATH.a) neurons, we measured dose-related influences of chronic alcohol exposure on nuclear PPARγ protein/activity and the influence of low-dose alcohol exposure on 2-hour oxygen-glucose deprivation (OGD)/24-hour reoxygenation-induced apoptosis. We found that low-dose alcohol exposure increased nuclear PPARγ protein/activity and protected against the OGD/reoxygenation-induced apoptosis. The beneficial effect of low-dose alcohol exposure on OGD/reoxygenation-induced apoptosis was abolished by GW9662. Our findings suggest that chronic consumption of low-dose alcohol protects the brain against I/R injury. The neuroprotective effect of low-dose alcohol consumption may be related to an upregulated PPARγ.
    Full-text · Article · Jul 2012 · PLoS ONE
  • Source
    Denise M Arrick · Hong Sun · Kaushik P Patel · William G Mayhan
    [Show abstract] [Hide abstract]
    ABSTRACT: Decreased dilation of cerebral arterioles via an increase in oxidative stress may be a contributing factor in the pathogenesis of diabetes-induced complications leading to cognitive dysfunction and/or stroke. Our goal was to determine whether resveratrol, a polyphenolic compound present in red wine, has a protective effect on cerebral arterioles during type 1 diabetes (T1D). We measured the responses of cerebral arterioles in untreated and resveratrol-treated (10 mg·kg(-1)·day(-1)) nondiabetic and diabetic rats to endothelial (eNOS) and neuronal (nNOS) nitric oxide synthase (NOS)-dependent agonists and to a NOS-independent agonist. In addition, we harvested brain tissue from nondiabetic and diabetic rats to measure levels of superoxide under basal conditions. Furthermore, we used Western blot analysis to determine the protein expression of eNOS, nNOS, SOD-1, and SOD-2 in cerebral arterioles and/or brain tissue from untreated and resveratrol-treated nondiabetic and diabetic rats. We found that T1D impaired eNOS- and nNOS-dependent reactivity of cerebral arterioles but did not alter NOS-independent vasodilation. While resveratrol did not alter responses in nondiabetic rats, resveratrol prevented T1D-induced impairment in eNOS- and nNOS-dependent vasodilation. In addition, superoxide levels were higher in brain tissue from diabetic rats and resveratrol reversed this increase. Furthermore, eNOS and nNOS protein were increased in diabetic rats and resveratrol produced a further increased eNOS and nNOS proteins. SOD-1 and SOD-2 proteins were not altered by T1D, but resveratrol treatment produced a decrease in SOD-2 protein. Our findings suggest that resveratrol restores vascular function and oxidative stress in T1D. We suggest that our findings may implicate an important therapeutic potential for resveratrol in treating T1D-induced cerebrovascular dysfunction.
    Full-text · Article · Jun 2011 · AJP Heart and Circulatory Physiology
  • Source
    Honggang Zhao · William G Mayhan · Denise M Arrick · Wanfen Xiong · Hong Sun
    [Show abstract] [Hide abstract]
    ABSTRACT: We examined the dose-related influence of alcohol consumption on cerebral ischemia/reperfusion (I/R) injury and the potential mechanism that accounts for the disparate effects of high-dose and low-dose alcohol consumption on cerebral I/R injury. Sprague-Dawley rats were fed a liquid diet with or without 1, 3, 5, or 6.4% (v/v) alcohol for 8 weeks and subjected to a 2-hour middle cerebral artery occlusion (MCAO). We evaluated the brain injury at 24 hours of reperfusion. In addition, we measured protein expression of NMDA receptor and excitatory amino acid transporters (EAATs) in parietal cortex and the effect of NMDA receptor antagonist, memantine, on 2-hour MCAO/24 h reperfusion-induced brain injury. Compared with non-alcohol-fed rats, the total infarct volume was not altered in 3 and 5% alcohol-fed rats but significantly reduced in 1% alcohol-fed rats and exacerbated in 6.4% alcohol-fed rats. Expression of the NMDA receptor subunit, NR1, was upregulated in 6.4% alcohol-fed rats, whereas expression of EAAT2 was downregulated in 6.4% alcohol-fed rats and upregulated in 1% alcohol-fed rats. Memantine reduced 2-hour MCAO/24 h reperfusion-induced brain injury in non-alcohol-fed and 6.4% alcohol-fed rats, but not in 1% alcohol-fed rats. The magnitude of reduction in the brain injury was greater in 6.4% alcohol-fed rats compared to non-alcohol-fed rats. Our findings suggest that chronic consumption of low-dose alcohol protects the brain against I/R injury, whereas chronic consumption of high-dose alcohol has detrimental effect on cerebral I/R injury. The disparate effects of low-dose and high-dose alcohol consumption on cerebral I/R may be related to an alteration in NMDA excitotoxicity.
    Full-text · Article · Feb 2011 · Alcoholism Clinical and Experimental Research
  • William G Mayhan · Denise M Arrick · Kaushik P Patel · Hong Sun
    [Show abstract] [Hide abstract]
    ABSTRACT: Our goal was to examine whether exercise training (ExT) could normalize impaired nitric oxide synthase (NOS)-dependent dilation of cerebral (pial) arterioles during type 1 diabetes (T1D). We measured the in vivo diameter of pial arterioles in sedentary and exercised nondiabetic and diabetic rats in response to an endothelial NOS (eNOS)-dependent (ADP), an neuronal NOS (nNOS)-dependent [N-methyl-D-aspartate (NMDA)], and a NOS-independent (nitroglycerin) agonist. In addition, we measured superoxide anion levels in brain tissue under basal conditions in sedentary and exercised nondiabetic and diabetic rats. Furthermore, we used Western blot analysis to determine eNOS and nNOS protein levels in cerebral vessels/brain tissue in sedentary and exercised nondiabetic and diabetic rats. We found that ADP and NMDA produced a dilation of pial arterioles that was similar in sedentary and exercised nondiabetic rats. In contrast, ADP and NMDA produced only minimal vasodilation in sedentary diabetic rats. ExT restored impaired ADP- and NMDA-induced vasodilation observed in diabetic rats to that observed in nondiabetics. Nitroglycerin produced a dilation of pial arterioles that was similar in sedentary and exercised nondiabetic and diabetic rats. Superoxide levels in cortex tissue were similar in sedentary and exercised nondiabetic rats, were increased in sedentary diabetic rats, and were normalized by ExT in diabetic rats. Finally, we found that eNOS protein was increased in diabetic rats and further increased by ExT and that nNOS protein was not influenced by T1D but was increased by ExT. We conclude that ExT can alleviate impaired eNOS- and nNOS-dependent responses of pial arterioles during T1D.
    No preview · Article · Dec 2010 · AJP Heart and Circulatory Physiology
  • Honggang Zhao · William G Mayhan · Denise M Arrick · Wanfen Xiong · Hong Sun
    [Show abstract] [Hide abstract]
    ABSTRACT:  Chronic alcohol consumption increases ischemic stroke and exacerbates ischemic brain injury. We determined the role of NAD(P)H oxidase in exacerbated ischemic brain injury during chronic alcohol consumption.  Sprague Dawley rats were fed a liquid diet with or without alcohol (6.4% v/v) for 8 weeks. We measured the effect of apocynin on 2-hour middle cerebral artery occlusion (MCAO)/24-hour reperfusion-induced brain injury. In addition, superoxide production and expression of NAD(P)H oxidase subunit, gp91phox, in the peri-infarct area were assessed. Chronic alcohol consumption produced a larger infarct volume, worse neurological score, and higher superoxide production. Acute (5 mg/kg, ip, 30 minutes before MCAO) and chronic treatment with apocynin (7.5 mg/kg/d in the diet, 4 weeks prior to MCAO) reduced infarct volume, improved neurological outcome, and attenuated superoxide production in alcohol-fed rats. Expression of gp91phox at basal conditions and following ischemia/reperfusion was greater in alcohol-fed rats compared to non-alcohol-fed rats. In addition, neurons are partially responsible for upregulated gp91phox during alcohol consumption. Our findings suggest that NAD(P)H oxidase may play an important role in exacerbated ischemic brain injury during chronic alcohol consumption.
    No preview · Article · Nov 2010 · Alcoholism Clinical and Experimental Research
  • Source
    William G Mayhan · Denise M Arrick · Hong Sun · Kaushik P Patel
    [Show abstract] [Hide abstract]
    ABSTRACT: Our goal was to determine whether exercise training (ExT) alleviates impaired nitric oxide synthase (NOS)-dependent dilation of pial arterioles during chronic exposure to nicotine. We measured dilation of cerebral (pial) arterioles in sedentary and exercised control and nicotine-treated (2 mg·kg(-1)·day(-1) for 4 wk via an osmotic minipump) rats to an endothelial NOS (eNOS)-dependent (ADP), a neuronal NOS (nNOS)-dependent [N-methyl-D-aspartic acid (NMDA)], and a NOS-independent (nitroglycerin) agonist. In addition, we harvested brain tissue from sedentary and exercised control and nicotine-treated rats to measure the production of superoxide anion and measured superoxide dismutase-1 (SOD-1) protein in cerebral microvessels using Western blot. We found that eNOS-and nNOS-dependent, but not NOS-independent, vasodilation was impaired in nicotine-treated compared with control rats. In addition, the production of superoxide anion (lucigenin chemiluminescence) was increased, and SOD-1 protein decreased, in rats treated with nicotine compared with control rats. Further, although ExT did not significantly affect eNOS- or nNOS-dependent vasodilation in control rats, ExT restored impaired eNOS- and nNOS-dependent responses in nicotine-treated rats. In addition, the increase in superoxide anion production observed in nicotine-treated rats was reduced by ExT, and SOD-1 protein was increased in nicotine-treated rats by ExT. We suggest that ExT restores impaired NOS-dependent dilation of pial arterioles during chronic exposure to nicotine by a mechanism related to the formation of superoxide anion.
    Full-text · Article · Oct 2010 · Journal of Applied Physiology
  • Source
    Denise M Arrick · William G Mayhan
    [Show abstract] [Hide abstract]
    ABSTRACT: Endothelin-1 has been implicated in the pathogenesis of many cardiovascular-related diseases, including diabetes. The goal of this study was to examine the influence of endothelin-1 receptors (ET(A)) in impaired responses of cerebral (pial) arterioles in type-1 diabetic rats. We measured responses of cerebral arterioles in non-diabetic rats to endothelial nitric oxide synthase (eNOS)-dependent (ADP), neuronal nitric oxide synthase (nNOS)-dependent (N-methyl-d-aspartic acid [NMDA]) and NOS-independent (nitroglycerin) agonists before and during application of BQ-123, an ET(A) receptor antagonist. In addition, we harvested brain tissue from non-diabetic and diabetic rats to measure the production of superoxide anion under basal conditions and during inhibition of ET(A) receptors. We found that diabetes specifically impaired eNOS- and nNOS-dependent reactivity of cerebral arterioles, but did not alter NOS-independent vasodilation. In addition, while BQ-123 did not alter responses in non-diabetic rats, BQ-123 restored impaired eNOS- and nNOS-dependent vasodilation in diabetic rats. Further, superoxide production was higher in brain tissue from diabetic rats compared with non-diabetic rats under basal conditions and BQ-123 decreased basal production of superoxide in diabetic rats. We suggest that activation of ET(A) receptors during type-1 diabetes mellitus plays an important role in impaired eNOS- and nNOS-dependent dilation of cerebral arterioles.
    Full-text · Article · Aug 2010 · Microcirculation (New York, N.Y.: 1994)
  • [Show abstract] [Hide abstract]
    ABSTRACT: The goal was to identify the role of NAD(P)H oxidase in cerebrovascular dysfunction in type 1 diabetes mellitus (T1D). In a first series of studies, rats were assigned to nondiabetic, diabetic (streptozotocin; 50 mg/kg IP), nondiabetic-apocynin (40 mg/kg/day in drinking water)-treated and diabetic-apocynin-treated groups. Two to three months later, the authors examined in vivo responses of pial arterioles to nitric oxide synthase (NOS)-dependent (acetylcholine and adenosine diphosphate (ADP)) and -independent (nitroglycerin) agonists. Next, they used Western blot analysis to examine protein levels for subunits of NAD(P)H oxidase in cerebral microvessels and parietal cortex tissue of nondiabetic and diabetic rats. Finally, they measured superoxide production by parietal cortex tissue in nondiabetic and diabetic rats. Acetylcholine- and ADP-induced dilatation of pial arterioles was impaired in diabetic compared to nondiabetic rats. In addition, while apocynin did not alter responses in nondiabetic rats, apocynin alleviated T1D-induced impairment of NOS-dependent vasodilatation. In addition, p47phox and gp91phox proteins were elevated in cerebral microvessels and parietal cortex tissue, respectively, of diabetic compared to nondiabetic rats. Further, basal production of superoxide was increased in diabetic compared to nondiabetic rats and apocynin decreased this basal production. The findings suggest that T1D impairs NOS-dependent reactivity of cerebral arterioles by a mechanism related to the formation of superoxide via activation of NAD(P)H oxidase.
    No preview · Article · Jan 2010 · Microcirculation
  • Source
    William G Mayhan · Denise M Arrick · Glenda M Sharpe · Hong Sun
    [Show abstract] [Hide abstract]
    ABSTRACT: Our goals were to determine whether acute exposure to nicotine alters nitric oxide synthase (NOS)-dependent responses of the basilar artery and to identify a potential role for activation of NAD(P)H oxidase in nicotine-induced impairment in NOS-dependent responses of the basilar artery. We measured in vivo diameter of the basilar artery in response to NOS-dependent (acetylcholine) and NOS-independent (nitroglycerin) agonists before and during an acute infusion of nicotine (2 microg/kg/min intravenously for 30 min followed by a maintenance dose of 0.35 microg/kg/min). In addition, we measured superoxide anion production (lucigenin chemiluminescence) by the basilar artery in response to nicotine in the absence or presence of apocynin. We found that NOS-dependent, but not NOS-independent, vasodilation was impaired during infusion of nicotine. In addition, treatment of the basilar artery with apocynin (100 microM, 30 min prior to infusion of nicotine) prevented nicotine-induced impairment in NOS-dependent vasodilation. Further, the production of superoxide anion was increased in the basilar artery by nicotine, and this increase could be inhibited by apocynin. Our findings suggest that acute exposure to nicotine impairs NOS-dependent dilation of the basilar artery by a mechanism that appears to be related to the release of superoxide anion. A possible source of superoxide may be via the activation of NAD(P)H oxidase.
    Full-text · Article · Mar 2009 · Nicotine & Tobacco Research
  • Source

    Preview · Article · Feb 2009 · Biophysical Journal
  • Source
    Denise M Arrick · Glenda M Sharpe · Hong Sun · William G Mayhan
    [Show abstract] [Hide abstract]
    ABSTRACT: We examined whether activation of angiotensin-1 receptors (AT1R) could account for impaired responses of cerebral arterioles during type 1 diabetes (T1D). First, we measured responses of cerebral arterioles in nondiabetic rats to eNOS-dependent (acetylcholine and adenosine diphosphate (ADP)) and -independent (nitroglycerin) agonists before and during application of angiotensin II. Next, we examined whether losartan could improve impaired responses of cerebral arterioles during T1D. In addition, we harvested cerebral microvessels for Western blot analysis of AT1R protein and measured production of superoxide anion by brain tissue under basal conditions and in response to angiotensin II in the absence or presence of losartan. We found that angiotensin II specifically impaired eNOS-dependent reactivity of cerebral arterioles. In addition, while losartan did not alter responses in nondiabetics, losartan restored impaired eNOS-dependent vasodilatation in diabetics. Further, AT1R protein was higher in diabetics compared to nondiabetics. Finally, superoxide production was higher in brain tissue from diabetics compared to nondiabetics under basal conditions, angiotensin II increased superoxide production in nondiabetics and diabetics, and losartan decreased basal (diabetics) and angiotensin II-induced production of superoxide (nondiabetics and diabetics). We suggest that activation of AT1R during T1D plays a critical role in impaired eNOS-dependent dilatation of cerebral arterioles.
    Full-text · Article · Jun 2008 · Brain Research
  • William G Mayhan · Denise M Arrick · Glenda M Sharpe · Hong Sun
    [Show abstract] [Hide abstract]
    ABSTRACT: Our goal was to identify the role of oxidative stress via activation of NAD(P)H oxidase in cerebrovascular dysfunction in aged rats. We examined the reactivity of cerebral arterioles in adult and aged Fisher-344 rats to endothelial nitric oxide synthase (eNOS)-dependent (acetylcholine and adenosine diphosphate [ADP]) and-independent (nitroglycerin) agonists before and during application of tempol, apocynin, and diphenyleneiodonium chloride (DPI). We used Western blot to examine subunits of NAD(P)H oxidase, eNOS, and superoxide dismutase (SOD-1) in cerebral microvessels and parietal cortex. Finally, we measured superoxide production by cortex tissue in adult and aged rats. Acetylcholine-and ADP-induced, but not nitroglycerin-induced, dilatation of cerebral arterioles was impaired in aged compared to adult rats. While tempol, apocynin, and DPI did not alter responses in adults, they alleviated impaired eNOS-dependent vasodilatation in aged rats, without influencing responses to nitroglycerin. eNOS and p67phox proteins were increased in cerebral microvessels from aged compared to adult rats. Further, p67phox and gp91phox proteins were increased, but SOD-1 protein was decreased, in cortex tissue of aged rats. Basal and agonist-induced production of superoxide was elevated in aged rats. Aging impairs eNOS-dependent reactivity of cerebral arterioles via an increase in superoxide produced by activation of NAD(P)H oxidase.
    No preview · Article · May 2008 · Microcirculation
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Inward rectifier potassium (K(IR)) channels appear to play an important role in the regulation of cerebral blood flow. Our goal was to examine the influence of chronic alcohol exposure on K(IR) channels in cerebral arterioles. Sprague-Dawley rats were fed liquid diets with or without alcohol for 8-12 weeks. Using intravital microscope, we measured diameter of pial arterioles in response to an inhibitor, BaCl(2), and an activator, KCl, of K(IR) channels in the absence and presence of a scavenger of reactive oxygen species, tempol, or an inhibitor of NAD(P)H oxidase, apocynin. Application of BaCl(2) (30 and 100 microM) produced dose-related vasoconstriction in non-alcohol-fed, but not in alcohol-fed rats. In addition, application of KCl (3, 10, and 30 mM) produced dose-related dilation in non-alcohol-fed and alcohol-fed rats, but the magnitude of vasodilatation was less in alcohol-fed rats. In contrast, nitroglycerin-induced vasodilation was similar in non-alcohol-fed and alcohol-fed rats. Superfusion of cranial window with tempol (0.1 mM) or apocynin (1 mM) did not alter baseline diameter and nitroglycerin-induced dilation of pial arterioles in non-alcohol-fed and alcohol-fed rats but significantly improved impaired KCl-induced dilation in alcohol-fed rats. Our findings suggest that chronic alcohol consumption impairs the role of K(IR) channels in basal tone and KCl-induced dilation of cerebral arterioles. In addition, impaired KCl-induced dilation of cerebral arterioles during alcohol consumption may be related to enhanced release of oxygen-derived free radicals via NAD(P)H oxidase.
    Full-text · Article · May 2008 · Microvascular Research

Publication Stats

294 Citations
66.14 Total Impact Points

Institutions

  • 2012-2016
    • Louisiana State University Health Sciences Center Shreveport
      • Department of Cellular Biology and Anatomy
      Shreveport, Louisiana, United States
  • 2011-2014
    • Louisiana State University in Shreveport
      Shreveport, Louisiana, United States
  • 2007-2011
    • University of Nebraska Medical Center
      • Department of Cellular and Integrative Physiology
      Omaha, Nebraska, United States
  • 2006-2009
    • University of Nebraska at Omaha
      • Department of Cellular and Integrative Physiology
      Omaha, Nebraska, United States