Mitsuhiro Goda

Okayama University, Okayama, Okayama, Japan

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Publications (22)40.72 Total impact

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    ABSTRACT: Background and purposePrevious studies demonstrated nicotine released protons from adrenergic nerves via stimulation of nicotinic acetylcholine receptors and activated transient receptor potential vanilloid-1 receptors (TRPV1) located on CGRP-containing vasodilator (CGRPergic) nerves, resulting in vasodilation. The present study investigated whether perivascular nerves release protons, which modulate axon-axonal neurotransmission.Experiment approachPerfusion pressure and pH levels of perfusate in rat perfused mesenteric vascular beds without endothelium were measured with a pressure transducer and a pH meter, respectively.Key resultsPeriarterial nerve stimulation induced initial vasoconstriction followed by long-lasting vasodilation and lowered pH levels in the perfusate. Cold-storage denervation of the preparation abolished pH-lowering and vascular responses to PNS. The adrenergic neuron blocker guanethidine inhibited PNS-induced vasoconstriction and lowering of pH levels, but not PNS-induced vasodilation. Capsaicin (CGRP depletor), capsazepine and ruthenium red (TRPV1 inhibitors) blunted PNS-induced pH-lowering and vasodilation. In denuded preparations, acetylcholine caused long-lasting vasodilation with pH-lowering, which were inhibited by capsaicin pretreatment and atropine, but not with guanethidine and mecamylamine. Capsaicin injection induced pH-lowering and vasodilation, which were abolished by ruthenium red. The study using a fluorescent pH indicator demonstrated application of nicotine, acetylcholine and capsaicin outside small mesenteric arteries caused a lowering of perivascular pH levels, which were abolished by Ca2+-free medium.Conclusion and implicationThese results suggest protons are released from perivascular adrenergic and CGRPergic nerves upon nerve excitement and released protons modulate CGRPergic nerve transmission.
    British Journal of Pharmacology 08/2014; 171(24). DOI:10.1111/bph.12878 · 4.99 Impact Factor
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    ABSTRACT: Vascular blood vessels have various types of cholinergic acetylcholine receptors (AChR), but the source of ACh has not been confirmed. Perivascular adrenergic nerves and non-adrenergic calcitonin gene-related peptide (CGRP)-containing (CGRPergic) nerves innervate rat mesenteric arteries and regulate vascular tone. However, function of cholinergic innervation remains unknown. The present study investigated cholinergic innervation by examining effects of cholinesterase inhibitor (neostigmine), a muscarinic AChR antagonist (atropine), and a nicotinic AChR antagonist (hexamethonium) on adrenergic nerve-mediated vasoconstriction and CGRPergic nerve-mediated vasodilation in rat mesenteric vascular beds without endothelium. In preparations treated with capsaicin (CGRP depletor) or in the presence of N-ω-nitro-L-arginine methyl ester (nonselective nitric-oxide synthase inhibitor), perivascular nerve stimulation (PNS; 2-12 Hz) evoked a frequency-dependent vasoconstriction. In the same preparations, exogenous norepinephrine induced a concentration-dependent vasoconstriction. Atropine, hexamethonium and neostigmine had no effect on vasoconstrictor responses to PNS and norepinephrine injections. In denuded preparations, these cholinergic agents did not affect the PNS (12 Hz)-evoked release of norepinephrine in perfusate. In preconstricted preparations without endothelium in the presence of guanethidine (adrenergic neuron blocker), PNS (1-4 Hz) induced a frequency-dependent vasodilation, which was not affected by atropine, hexamethonium and neostigmine. In denuded preparations treated with capsaicin and guanethidine, PNS did not induce vascular responses and atropine, neostigmine and physostigmine had no effect on PNS. Immunohistochemistry study showed choline acetyltransferase-immunopositive fibers, which were resistant to capsaicin and 6-hydroxydopamine (adrenergic toxin). These results suggest that rat mesenteric arteries have cholinergic innervation, which is different from adrenergic and capsaicin-sensitive nerves and not associated with vascular tone regulation.
    AJP Regulatory Integrative and Comparative Physiology 10/2012; 303(11). DOI:10.1152/ajpregu.00317.2012 · 3.53 Impact Factor
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    ABSTRACT: Rat mesenteric arteries were maintained by both adrenergic vasoconstrictor nerves and calcitonin gene-related peptide (CGRP) vasodilator nerves. However, functions of these nerves in a pathophysiological state have not fully been analyzed. The use of disease models developed genetically in mice is expected to clarify neural function of perivascular nerves. Thus, we investigated basic mouse vascular responses. Mesenteric vascular beds isolated from male C57BL/6 mouse were perfused with Krebs solution and perfusion pressure was measured. Periarterial nerve stimulation (PNS, 8 - 24 Hz) induced frequency-dependent vasoconstriction, which increased flow rate-dependently. PNS-induced vasoconstriction was abolished by tetrodotoxin (neurotoxin) and guanethidine (adrenergic neuron blocker) and blunted by prazosin (α(1)-adrenoceptor antagonist). Injection of norepinephrine caused vasoconstriction, which was abolished by prazosin. In preparations with active tone, PNS (1 - 8 Hz) induced frequency-dependent vasodilation, which was inhibited by tetrodotoxin, capsaicin (CGRP depletor), and CGRP8-37 (CGRP-receptor antagonist). Injections of CGRP, acetylcholine, and sodium nitroprusside induced vasodilations. Vasodilator response to CGRP was inhibited by CGRP8-37. Immunohistochemical study showed innervation of tyrosine hydroxylase- and CGRP-immunopositive fibers in mesenteric arteries and veins. These results suggest that male mouse mesenteric vascular beds are useful for studying neural regulation of mesenteric arteries, which are innervated by adrenergic and CGRPergic nerves regulating vascular tone.
    Journal of Pharmacological Sciences 06/2012; 119(3):260-70. DOI:10.1254/jphs.12014FP · 2.11 Impact Factor
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    ABSTRACT: Angiogenesis, or new blood vessel formation, is critical for the growth and spread of tumors. The vascular tone and tissue blood flow are maintained and regulated by perivascular nerves. However, many studies have reported that tumor neovascular vessels have no innervation of perivascular nerves. We have shown that nerve growth factor (NGF) facilitated perivascular innervation and suppressed the tumor growth. From these results, we hypothesized that the neuronal regulation of blood flow toward tumors via perivascular nerves may lead suppression of the tumor growth. Therefore, the aim of this study is to investigate effect of NGF on distribution of perivascular nerves and neovessel form in tumor tissues, which were generated by mouse corneal micropocket method. A gel, which contained DU145 prostate carcinoma cells, was implanted into the mouse corneal. NGF or saline was subcutaneously administered using an osmotic mini-pump. After 1 week, the distribution of perivascular nerves in mouse corneal were immunohistochemically studied. Also, the density of neovessels (immunocytochemically stained CD31) and smooth muscles (α-smooth muscle actin; SMA) in tumor tissues was quantified by the computer-assisted image processing. Four days after implantation of tumor cells in mouse corneal, many neovessels generated from corneal limbal vessels were observed in tumor tissues. Treatment of mouse with NGF resulted in innervation of perivascular nerves around tumor neovessels, but not observed in saline-treated group. NGF treatment increased SMA-, but not CD31-, immunopositive cells. These results suggest that NGF may facilitate innervations of perivascular nerve to regulate the blood flow in tumor neovessels.
    YAKUGAKU ZASSHI 01/2012; 132(2):157-60. DOI:10.1248/yakushi.132.157 · 0.31 Impact Factor
  • Mitsuhiro Goda · Yui Yamamoto
    YAKUGAKU ZASSHI 04/2011; 131(4):485. DOI:10.1248/yakushi.131.485 · 0.31 Impact Factor
  • ChemInform 03/2011; 42(13). DOI:10.1002/chin.201113271
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    ABSTRACT: The present study was designed to investigate involvement of angiotensin (Ang) II type 2 receptors (AT2R) in restoration of perivascular nerve innervation injured by topical phenol treatment. Male Wistar rats underwent in vivo topical application of 10% phenol around the superior mesenteric artery to induce nerve injure. Phenol treatment markedly reduced densities of both calcitonin gene-related peptide (CGRP)-like immunoreactivity (LI)- and neuropeptide Y (NPY)-LI-containing fibers. NGF restored densities of both nerve fibers to the Sham control level. Coadministration of Ang II and losartan (AT1R antagonist) significantly increased the density of CGRP-LI-fibers but not NPY-LI-fibers compared with saline control. The increase of the density of CGRP-LI-fibers by coadministration of Ang II and losartan was suppressed by adding PD123319 (AT2R antagonist). Furthermore, NGF-induced CGRP-LI nerve regeneration was inhibited by PD123319 treatment. NGF-induced increase of AT2R mRNA level was significantly suppressed by AT1R antagonist treatment in phenol treated rats dorsal root ganglia. These results suggest that selective stimulation of AT2R by Ang II facilitates reinnervation of mesenteric perivascular CGRP-containing nerves injured by topical phenol application in the rat.
    Yakugaku zasshi journal of the Pharmaceutical Society of Japan 02/2011; 130(9):1189-95. DOI:10.1002/chin.201105263 · 0.31 Impact Factor
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    ABSTRACT: The aim of this study was to investigate age-related changes in the density of calcitonin gene-related peptide (CGRP)-containing nerve fibers in spontaneously hypertensive rats (SHR) and the effects of long-term inhibition of the renin-angiotensin system on these changes. An age-related decrease in the density of CGRP-like immunoreactive (LI)-containing nerve fibers but not neuropeptide Y (NPY)-LI-containing sympathetic nerve fibers was found in the mesenteric artery of SHR but not Wistar-Kyoto rats (WKY). The density of NPY-LI-containing nerve fibers was significantly greater in SHR than in WKY. SHR were treated for 7 weeks with angiotensin-converting enzyme inhibitor (0.005% temocapril), angiotensin II type-1 (AT1) receptor antagonist (0.025% losartan), or vasodilator (0.01% hydralazine) in their drinking water. Each drug treatment significantly lowered the systolic blood pressure measured using the tail-cuff method. Long-term treatment of SHR with temocapril and losartan significantly increased the density of CGRP-LI-containing nerve fibers in mesenteric arteries. Furthermore, to clarify the effect of the angiontensin II type-2 (AT2) receptor in the restoration of perivascular nerve innervation, we used the phenol-injured rat model, in which the perivascular nerves are markedly reduced by the topical application of phenol. Activation of AT2R significantly restored CGRP-LI innervation in phenol-injured rats. These results suggest that selective stimulation of AT2 receptors facilitates reinnervation of mesenteric perivascular CGRP-containing nerves.
    Yakugaku zasshi journal of the Pharmaceutical Society of Japan 11/2010; 130(11):1421-5. DOI:10.1248/yakushi.130.1421 · 0.31 Impact Factor
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    ABSTRACT: Immunohistochemical study of rat mesenteric arteries showed dense innervation of adrenergic nerves, calcitonin gene-related peptide (CGRP)-containing nerves (CGRPergic nerves), nitric oxide-containing nerves (nitrergic nerves). Double-immunostaining revealed that most CGRPergic or nitrergic nerves were in close contact with adrenergic nerves. CGRPergic and transient receptor potential vanilloid-1 (TRPV1)-immunopositive nerves appeared in the same neurone. In rat perfused mesenteric vascular beds without endothelium and with active tone, perfusion of nicotine, or bolus injection of capsaicin and acetylcholine and periarterial nerve stimulation (PNS) lowered pH levels of out flowed perfusate concomitant with vasodilation. Cold-storage denervation of preparations abolished pH lowering induced by nicotine and PNS. Guanethidine inhibited PNS- and nicotine-, but not acetylcholine- and capsaicin-, induced pH lowering. Pharmacological analysis showed that protons were released not only from adrenergic nerves but also from CGRPergic nerves. A study using a fluorescent pH indicator demonstrated that nicotine, acetylcholine and capsaicin applied outside small mesenteric artery lowered perivascular pH levels, which were not observed in Ca(2+) free medium. Exogenously injected hydrochloric acid in denuded preparations induced pH lowering and vasodilation, which was inhibited by denervation, TRPV1 antagonists and capsaicin without affecting pH lowering. These results suggest that excitement of adrenergic nerves releases protons to activate TRPV1 in CGRPergic nerves and thereby induce vasodilation. It is also suggested that CGRPergic nerves release protons with exocytosis to facilitate neurotransmission via a positive feedback mechanism.
    Acta Physiologica 09/2010; 203(1):3-11. DOI:10.1111/j.1748-1716.2010.02197.x · 4.25 Impact Factor
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    ABSTRACT: Neuronal nitric oxide (NO) has been shown to modulate perivascular adrenergic neurotransmission by inhibiting noradrenaline release from terminals in rat mesenteric arteries. This study was conducted to investigate changes in the inhibitory function of NO-containing nerves (nitrergic nerves) in mesenteric vascular beds of 2-kidney, 1-clip renovascular hypertensive rats (2K1C-RHR). Rat mesenteric vascular beds without endothelium were perfused with Krebs solution and the perfusion pressure was measured. In preparations from sham-operated rats (control) and 2K1C-RHRs, vasoconstriction induced by periarterial nerve stimulation (PNS; 2-8 Hz), but not vasoconstriction induced by exogenously injected noradrenaline (0.5, 1.0 nmol), was markedly facilitated in the presence of a nonselective NO synthase (NOS) inhibitor, N-omega-nitro-L-arginine methyl ester (L-NAME) (100 microM). The facilitatory effect of L-NAME in preparations from 2K1C-RHR was smaller than that in control preparations. L-NAME augmented PNS-evoked noradrenaline release, which was smaller in 2K1C-RHRs than in controls. The expression of neuronal NO synthase (nNOS) measured by western blotting in mesenteric arteries from 2K1C-RHRs was significantly decreased compared with control arteries. Immunohistochemical staining of mesenteric arteries showed dense innervation of nNOS-immunopositive nerves that was significantly smaller in arteries from 2K1C-RHR than that in control arteries. Mesenteric arteries were densely innervated by tyrosine hydroxylase-immunopositive nerves, which coalesced with nNOS-immunopositive nerves. These results suggest that the inhibitory function of nitrergic nerves in adrenergic neurotransmission is significantly decreased in 2K1C-RHRs. This functional alteration based on the decrease in nNOS expression and nitrergic innervation leads to enhanced adrenergic neurotransmission and contributes to the initiation and development of renovascular hypertension.
    Hypertension Research 04/2010; 33(5):485-91. DOI:10.1038/hr.2010.48 · 2.94 Impact Factor
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    ABSTRACT: Nerve growth factor (NGF) facilitates reinnervation of perivascular nerves that regulate vascular tone and blood flow. This study investigated whether NGF prevents tumor growth by promoting neuronal regulation of tumor blood flow. The growth rate of DU145 prostate carcinoma cells subcutaneously implanted into nude mice was significantly inhibited by subcutaneous NGF administration. Significant suppression of tumor growth continued after withdrawing NGF. NGF increased vascular smooth muscle cells in tumor tissues, but had no cytotoxic action on tumor cells in vitro. These results suggest that NGF prevents tumor growth via an indirect effect, probably innervation or maturation of the tumor neovasculature.
    Journal of Pharmacological Sciences 03/2010; 112(4):463-6. DOI:10.1254/jphs.09354SC · 2.11 Impact Factor
  • ChemInform 06/2009; 40(26). DOI:10.1002/chin.200926277
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    ABSTRACT: The role of nitric oxide (NO)-containing nerves in adrenergic neurotransmission in hypertension was studied in mesenteric resistance arteries without endothelium in 2-kidney-1-clip renal hypertensive rats (2K-1C RHR) and sham-operated normotensive rats (Sham-R). Mesenteric vascular beds isolated from 2K-1C RHR and Sham-R were perfused with Krebs solution and changes in perfusion pressure were measured with a pressure transducer. Perfusion of a NO synthase inhibitor, N-omega-nitro-L-arginine methyl ester (L-NAME), markedly augmented vasoconstrictor responses to periarterial nerve stimulation (PNS) without affecting vasoconstriction induced by exogenously injected noradrenaline. L-NAME significantly increased the neurogenic release of NA evoked by PNS in both 2K-1C RHR and Sham-R preparations. The facilitatory effect of L-NAME based on the inhibition of NO production in 2K-1C RHR was less than that in Sham-R. These results suggest that the function of NO-containing nerves, which presynaptically inhibit adrenergic neurotransmission, is decreased in the renovascular hypertensive model rat.
    Yakugaku zasshi journal of the Pharmaceutical Society of Japan 03/2009; 129(2):185-9. DOI:10.1248/yakushi.129.185 · 0.31 Impact Factor
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    ABSTRACT: Hepatic growth factor (HGF) has neurotrophic effects in the motor neurons and central nervous system. However, there has been no report about the neurotrophic action on perivascular nerves innervating the resistance artery. We investigated whether HGF can restore innervation or function of perivascular nerves, including neuropeptide Y (NPY)-containing sympathetic adrenergic nerves and calcitonin gene-related peptide (CGRP)-containing nerves, in rat mesenteric artery. To investigate HGF-mediated neurotrophic effects, Wistar rats under pentobarbital-Na anesthesia underwent in vivo perivascular denervation by topical application of phenol on the superior mesenteric artery, and then HGF or nerve growth factor (NGF) was administered for 7 days using an osmotic mini-pump after phenol-treatment. HGF significantly increased the density and number of CGRP-like immunoreactivity (LI)-containing nerve fibers compared with saline administration, while HGF did not affect the density of NPY-containing adrenergic nerve fibers. After 7-day treatment with HGF and phenol, the vascular response of vasodilation was recovered from nerve injury by phenol treatment, but vasoconstriction was not. HGF and NGF induced neurite outgrowth in rat cultured dorsal root ganglia (DRG). These results suggest that HGF has a specific neurotrophic action on reinnervation of vascular CGRP-LI-containing nerve fibers in the rat mesenteric artery and DRG.
    Journal of Pharmacological Sciences 01/2009; 108(4):495-504. DOI:10.1254/jphs.08225FP · 2.11 Impact Factor
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    ABSTRACT: Royal jelly (RJ) is known to contain excellent nutrition and a variety of biological activities. The present study was designed to investigate the effects of RJ on insulin resistance (hyperinsulinemia) in fructose-drinking rats (FDR; insulin resistance animal model). Male Wistar rats (6 weeks old) received 15% fructose solution in drinking water for 8 weeks. FDR showed significant increases in plasma levels of insulin and triglyceride, Homeostasis Model Assessment ratio (HOMA-R, an index of insulin resistance), and systolic blood pressure, but not blood glucose levels, when compared with control rats. RJ (100, 300 mg/kg, p.o.) treatment for 8 weeks significantly decreased the plasma levels of insulin and triglyceride, HOMA-R, without affecting blood glucose or total cholesterol levels and tended to lower systolic blood pressure. In isolated and perfused mesenteric vascular beds of FDR, RJ treatment resulted in a significant reduction in sympathetic nerve-mediated vasoconstrictor response to periarterial nerve stimulation (PNS) and tended to increase the calcitonin gene-related peptide (CGRP) nerve-mediated vasodilator response to PNS, compared with those in untreated FDR. However, RJ treatment did not significantly affect norepinephrine-induced vasoconstriction or CGRP-induced vasodilation. These results suggest that RJ could be an effective functional food to prevent insulin resistance associated with the development of hypertension.
    Biological & Pharmaceutical Bulletin 12/2008; 31(11):2103-7. DOI:10.1248/bpb.31.2103 · 1.78 Impact Factor
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    ABSTRACT: The present study was designed to investigate involvement of angiotensin II (Ang II) type 2 receptors (AT2 receptors) in restoration of perivascular nerve innervation injured by topical phenol treatment. Male Wistar rats underwent in vivo topical application of 10% phenol around the superior mesenteric artery. After phenol treatment, animals were subjected to immunohistochemistry of the third branch of small arteries, Western blot analysis of AT2 receptor protein expression in dorsal root ganglia (DRG) and studies of mesenteric neurogenic vasoresponsiveness. Ang II (750 ng/kg/day), nerve growth factor (NGF; 20 microg/kg/day) and PD123,319 (AT2 receptor antagonist; 10 mg/kg/day) were intraperitoneally administered for 7 days using osmotic mini-pumps immediately after topical phenol treatment. Losartan (AT1 receptor antagonist) was administered in drinking water (0.025%). Phenol treatment markedly reduced densities of both calcitonin gene-related peptide (CGRP)-like immunoreactivity (LI) and neuropeptide Y (NPY)-LI-containing fibers. NGF restored densities of both nerve fibers to the sham control level. Coadministration of Ang II and losartan significantly increased the density of CGRP-LI-fibers but not NPY-LI-fibers compared with saline control. The increase of the density of CGRP-LI-fibers by coadministration of Ang II and losartan was suppressed by adding PD123,319. Coadministration of Ang II and losartan ameliorated reduction of CGRP nerve-mediated vasodilation of perfused mesenteric arteries caused by phenol treatment. The AT2 receptor protein expression detected in DRG was markedly increased by NGF. These results suggest that selective stimulation of AT2 receptors by Ang II facilitates reinnervation of mesenteric perivascular CGRP-containing nerves injured by topical phenol application in the rat.
    Neuroscience 01/2008; 150(3):730-41. DOI:10.1016/j.neuroscience.2007.09.026 · 3.33 Impact Factor
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    ABSTRACT: Propolis, a honeybee product, contains a variety of biologically active substances. The present study was designed to investigate the effects of propolis on insulin resistance induced by fructose-drinking rats (FDR; type 2 diabetic animal model). Male Wistar rats (6 weeks old) received 15% fructose solution in drinking water for 8 weeks. FDR showed significant increases in plasma levels of insulin, Homeostasis Model Assessment ratio (HOMA-R, an index of insulin resistance), body weight, and systolic blood pressure but not blood glucose levels, when compared with control rats. Brazilian propolis extract (100 and 300 mg/kg, p.o.) treatment for 8 weeks significantly decreased the plasma level of insulin, HOMA-R, and body weight, increased plasma triglyceride levels without affecting blood glucose and total cholesterol levels, and tended to decrease systolic blood pressure. In isolated and perfused mesenteric vascular beds of FDR, propolis treatment resulted in a significant reduction of sympathetic nerve-mediated vasoconstrictor response to periarterial nerve stimulation (PNS; 8 Hz) and tended to increase the calcitonin gene-related peptide (CGRP) nerve-mediated vasodilator response to PNS, compared with those in untreated FDR. However, propolis treatment did not significantly affect norepinephrine-induced vasoconstriction and CGRP-induced vasodilation. These results suggest that propolis could be an effective functional food to prevent the development of insulin resistance.
    Yakugaku zasshi journal of the Pharmaceutical Society of Japan 01/2008; 127(12):2065-73. DOI:10.1248/yakushi.127.2065 · 0.31 Impact Factor
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    ABSTRACT: Our previous report showed that innervation of calcitonin gene-related peptide (CGRP)- and neuropeptide Y (NPY)-containing nerves in rat mesenteric resistance arteries was markedly reduced by topical application of phenol, and that nerve growth factor (NGF) facilitates the reinnervation of both nerves. We also demonstrated that a CGRP superfamily peptide, adrenomedullin, is distributed in perivascular nerves of rat mesenteric resistance arteries. In the present study, we investigated the influence of adrenomedullin on the reinnervation of mesenteric perivascular nerves following topical phenol treatment. Under pentobarbital-Na anesthesia, 8-week-old Wistar rats underwent in vivo topical application of phenol (10% phenol in 90% ethanol) to the superior mesenteric artery proximal to the bifurcation of the abdominal aorta. After the treatment, the animals were subjected to immunohistochemistry of the third branch of small arteries proximal to the intestine and to vascular responsiveness testing on day 7. Topical phenol treatment caused marked reduction of the density of NPY-like immunoreactive (LI)- and CGRP-LI nerve fibers in the arteries. Adrenomedullin (360 or 1000 ng/h) or NGF (250 ng/h), which was administered intraperitoneally for 7 days using an osmotic mini-pump immediately after topical phenol treatment, significantly increased the density of CGRP-LI- and NPY-LI nerve fibers compared with saline. Treatment with adrenomedullin (1000 ng/h) or NGF restored adrenergic nerve-mediated vasoconstriction and CGRP nerve-mediated vasodilation in the perfused mesenteric artery treated topically with phenol. These results suggest that adrenomedullin, like NGF, has a facilitatory effect on the reinnervation of perivascular nerves.
    Neuroscience 02/2007; 144(2):721-30. DOI:10.1016/j.neuroscience.2006.09.031 · 3.33 Impact Factor
  • 01/2007; 33(8):674-679. DOI:10.5649/jjphcs.33.674
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    ABSTRACT: We have previously shown that age-related reduction of innervation and function in mesenteric perivascular calcitonin gene-related peptide-containing vasodilator nerves takes place in spontaneously hypertensive rats. The present study was performed to investigate innervation and functional changes in perivascular calcitonin gene-related peptide- and adrenergic neuropeptide Y-containing nerves after topical treatment with phenol, which damages nerve fibers, around the rat superior mesenteric artery. Under pentobarbital-Na anesthesia, 8-week-old Wistar rats underwent in vivo topical application of phenol (10% phenol in 90% ethanol) or saline (sham rats) to the superior mesenteric artery proximal to the bifurcation of the abdominal aorta. After the treatment, the animals were subjected to immunohistochemistry of the 3rd branch of small arteries proximal to the intestine and to vascular responsiveness testing on day 3 through day 14. The innervation levels of calcitonin gene-related peptide-like immunoreactivity containing fibers and neuropeptide Y-like immunoreactivity containing fibers were markedly reduced on day 3 to day 14 and on day 5 to day 14 after the treatment, compared with those in sham-operated rats, respectively. In perfused mesenteric vascular beds isolated from phenol-treated rats, adrenergic nerve-mediated vasoconstriction and calcitonin gene-related peptide nerve-mediated vasodilation in response to periarterial nerve stimulation (2-12 Hz) were significantly decreased on day 3 and day 7. Neurogenic release of norepinephrine in phenol-treated rats on day 7 was significantly smaller that that in sham-operated rats. Nerve growth factor content in the mesenteric arteries of phenol-treated rats was significantly lower than that in sham-operated rats. Administration of nerve growth factor using osmotic mini-pumps for 7 days after the phenol treatment resulted in greater density of calcitonin gene-related peptide- and neuropeptide Y-like immunoreactivity fibers than in phenol-treated rats and restored decreased vascular responses to periarterial nerve stimulation. These results suggest that topical phenol-treatment of the mesenteric artery effectively induces functional denervation of perivascular nerves, which can be prevented or reversed by nerve growth factor treatment.
    Neuroscience 09/2006; 141(2):1087-99. DOI:10.1016/j.neuroscience.2006.04.001 · 3.33 Impact Factor

Publication Stats

140 Citations
40.72 Total Impact Points

Institutions

  • 2005–2014
    • Okayama University
      • Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
      Okayama, Okayama, Japan
  • 2012
    • Setsunan University
      Ōsaka, Ōsaka, Japan
    • Niigata University
      • Graduate School of Medical and Dental Sciences
      Niahi-niigata, Niigata, Japan
  • 2011
    • Okayama University of Science
      • Department of Life Science
      Okayama, Okayama, Japan