Augmented adrenergic vasoconstriction in hypertensive diabetic obese Zucker rats.

Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
AJP Heart and Circulatory Physiology (Impact Factor: 4.01). 04/2002; 282(3):H816-20. DOI: 10.1152/ajpheart.00695.2001
Source: PubMed

ABSTRACT This study examined skeletal muscle microvessel reactivity to constrictor stimuli in obese (OZR) versus lean Zucker rats (LZR). Gracilis arteries from both rat groups were isolated, cannulated with glass micropipettes, and viewed via television microscopy. Changes in vessel diameter were measured with a video micrometer. Arterial constriction to norepinephrine was elevated in OZR versus LZR, although vasoconstrictor reactivity to endothelin and angiotensin II was unaltered. Differences in reactivity between vessels of LZR and OZR were not explained by the loss of either endothelial nitric oxide synthase or beta-adrenergic receptor function. Reactivity of in situ cremasteric arterioles of OZR to norepinephrine was elevated versus LZR. Treatment with prazosin increased the diameter of in vivo gracilis arteries of OZR to levels determined in LZR and also normalized blood pressure in OZR. These results suggest that the constrictor reactivity of skeletal muscle microvessels in OZR is heightened in response to alpha-adrenergic stimuli and that development of diabetes in OZR may be associated with impaired skeletal muscle perfusion and hypertension due to microvessel hyperreactivity in response to sympathetic stimulation.

  • [Show abstract] [Hide abstract]
    ABSTRACT: OBJECTIVE: To use the obese Zucker rat (OZR) model of the metabolic syndrome to determine the impact of dilator stimuli on myogenic activation (MA) of gracilis arterioles (GA) and middle cerebral arteries (MCA). We tested the hypothesis that increased oxidant stress and thromboxane A2 (TxA2 ) exacerbate MA, and prevent its blunting with dilator stimuli, in OZR METHODS: GA/MCA from OZR and lean Zucker rats (LZR) were pressurized ex vivo. MA was determined under control conditions and following challenge with acetylcholine, hypoxia and adenosine. Responses were also evaluated after pre-treatment with TEMPOL (antioxidant) and SQ-29548 (PGH2 /TxA2 receptor antagonist) RESULTS: MA was increased (and dilator responses decreased) in GA/MCA from OZR, dependent on the endothelium and ROS. In GA, the impact of ROS on MA and dilator effects was largely via TxA2 , while in MCA, this appeared was more dependent on NO bioavailability. Intrinsic responses of GA/MCA to carbacyclin, U46619, and NO donors were similar between strains. CONCLUSIONS: A developing ROS-based endothelial dysfunction in MCA and GA of OZR contributes to an enhanced MA of these vessels. While treatment of GA/MCA with TEMPOL attenuates MA in OZR, the mechanistic contributors to altered MA, distal to ROS, differ between the two resistance vessels. © 2013 John Wiley & Sons Ltd.
    Microcirculation (New York, N.Y.: 1994) 03/2013; 20(7). DOI:10.1111/micc.12056 · 2.26 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background. Alpha-adrenergic-mediated vasoconstriction is greater during simulated exercise in animal models of metabolic syndrome (MetSyn) when compared with control animals. In attempt to translate such findings to humans, we hypothesized adults with MetSyn (n = 14, 35±3 years) would exhibit greater α-adrenergic responsiveness during exercise when compared with age-matched healthy controls (n = 16, 31±3 years). Methods. We measured muscle sympathetic nerve activity (MSNA, microneurography) and forearm blood flow (FBF, Doppler ultrasound) during dynamic forearm exercise (15% of maximal voluntary contraction). Alpha-adrenergic agonists (phenylephrine and clonidine) and antagonist (phentolamine) were infused intra-arterially to assess α-adrenergic receptor responsiveness and restraint, respectively. Results. Resting MSNA was ∼35% higher in MetSyn adults (p<0.05) but did not change in either group with dynamic exercise. Clonidine-mediated vasoconstriction was greater in MetSyn adults (p<0.01). Group differences in vascular responses to phenylephrine and phentolamine were not detected (p>0.05). Interestingly, exercise-mediated vasodilation was greater in MetSyn (p<0.05). Conclusion. Adults with MetSyn exhibit greater resting MSNA and clonidine-mediated vasoconstriction, yet preserved functional sympatholysis and higher exercise blood flow during low-intensity handgrip exercise when compared with age-matched healthy controls. These results suggest adults with MetSyn exhibit compensatory vascular control mechanisms capable of preserving blood flow responses to exercise in the face of augmented sympathetic adrenergic activity.This article is protected by copyright. All rights reserved
    Experimental physiology 03/2014; 99(9). DOI:10.1113/expphysiol.2014.078048 · 2.87 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Introduction Microvascular dysfunction is associated with metabolic syndrome (MetS) and its components. The objective of our study was to assess macro and microvascular abnormalities in MetS and compare the strength of association of the ankle blood pressure index (ABPI), toe blood pressure index (TBPI) and hemorheological parameters with MetS. Materials and methods 100 participants were recruited from a rural Australian town. Anthropometric measurements were taken along with blood pressures (BP) at the arm, the ankle and the big toe for calculating ABPI and TBPI. Whole blood viscosity (WBV), erythrocyte aggregation, erythrocyte deformability, lipid profile and blood sugar level were analysed. Recruited participants were classified into MetS and non-MetS following National Cholesterol Education Programl Adult Treatment Panel III definition. Data were analysed by IBM SPSS 20 software. Results WBV and erythrocyte aggregation were higher whereas erythrocyte deformability was lower in participants with MetS when compared to participants without MetS. Age, sex and diabetes mellitus adjusted odds ratio for predicting MetS was not significant for ABPI and TBPI whereas it was significant for hemorheological parameters. Receiver Operating Characteristics curve showed that TBPI better classified MetS than ABPI but association of hemorheological parameters were superior to that of ABPI and TBPI with MetS. Conclusions Both microcirculation defects and macrovascular circulation defects were present in MetS. The concurrences of the components of MetS could have an additive effect in enhancing alterations in hemorheological parameters which may give rise to severe microvasculopathy. The association of hemorheological parameters were stronger than the association of TBPI and ABPI with MetS.
    Microvascular Research 07/2014; 95:31-36. DOI:10.1016/j.mvr.2014.06.013 · 2.43 Impact Factor