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: 3.63). 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: Young healthy adults exhibit an inverse linear relationship between muscle sympathetic nerve activity (MSNA) and α-adrenergic responsiveness. This balance may be reversed in metabolic syndrome (MetSyn) given animal models exhibit increased sympathetic activity and α-mediated vasoconstriction. We hypothesized humans with MetSyn would demonstrate increased α-adrenergic vasoconstriction and the inverse relationship between MSNA and adrenergic responsiveness would be lost. We measured MSNA (microneurography of the peroneal nerve) and forearm blood flow (FBF, Doppler ultrasound) in 16 healthy control subjects (31±3 years) and 14 adults with MetSyn (35±3 years; p>0.05) during local administration of α-adrenergic agonists (phenylephrine, PE α1; clonidine, CL α2). MSNA was greater in MetSyn subjects when compared with healthy controls (p<0.05). A group difference in vasoconstriction to PE was not detected (p=0.08). The level of α1-mediated vasoconstriction was inversely related to MSNA in control subjects (r=0.5, p=0.04); this balance between MSNA and α1-responsiveness was lost in adults with MetSyn. MetSyn subjects exhibited greater vasoconstriction to CL infusion when compared with healthy controls (p<0.01). A relationship between MSNA and α2-mediated vasoconstriction was not detected in either group. In summary, altered neurovascular control in human MetSyn is receptor-specific. The observed uncoupling between MSNA and α1-adrenergic responsiveness and increased α2 -vasoconstriction may lead to reduced FBF, altered flow distribution, and/or severe hypertension with the progression toward diabetes and cardiovascular disease.
    The Journal of Physiology 10/2012; · 4.38 Impact Factor
  • [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; · 2.37 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: Rice bran enzymatic extract (RBEE) used in this study has shown beneficial activities against dyslipidemia, hyperinsulinemia and hypertension. Our aim was to investigate the effects of a diet supplemented with RBEE in vascular impairment developed in obese Zucker rats and to evaluate the main mechanisms mediating this action. METHODS AND RESULTS: Obese Zucker rats were fed a 1% and 5% RBEE-supplemented diet (O1% and O5%). Obese and their lean littermates fed a standard diet were used as controls (OC and LC, respectively). Vascular function was evaluated in aortic rings in organ baths. The role of nitric oxide (NO) was investigated by using NO synthase (NOS) inhibitors. Aortic expression of endothelial NOS (eNOS), inducible NOS (iNOS), tumor necrosis factor (TNF)-α and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits and superoxide production in arterial wall were determined. Endothelial dysfunction and vascular hyperreactivity to phenylephrine in obese rats were ameliorated by RBEE treatment, particularly with 1% RBEE. Up-regulation of eNOS protein expression in RBEE-treated aortas should contribute to this activity. RBEE attenuated vascular inflammation by reducing aortic iNOS and TNF-α expression. Aortas from RBEE-treated groups showed a significant decrease of superoxide production and down-regulation of NADPH oxidase subunits. CONCLUSION: RBEE treatment restored endothelial function and vascular contractility in obese Zucker rats through a reduction of vascular inflammation and oxidative stress. These results show the nutraceutical potential of RBEE to prevent obesity-related vascular complications.
    The Journal of nutritional biochemistry 03/2013; · 4.29 Impact Factor