Effects of trans- versus cis-resveratrol on adrenergic contractions of the rat tail artery and role of endothelium.

The health benefits of the natural polyphenol trans-resveratrol may play an important role in preventing a variety of diseases. Resveratrol has been shown to reduce blood pressure and improve metabolic diseases such as type 2 diabetes mellitus and obesity. Our previous studies examined the role of K channels in the vasorelaxation responses to trans-resveratrol in the rat tail artery.

Resveratrol's Potential in the Adjunctive Management of Cardiovascular Disease, Obesity, Diabetes, Alzheimer Disease, and Cancer.

Resveratrol is a naturally occurring polyphenol that can be found in several human dietary sources, including red wine; many plants, especially grapes, berries, and nuts; and nutritional supplements. Findings from numerous preclinical experiments and clinical trials in humans suggest that resveratrol may play an important role in managing or preventing a variety of diseases. Some of the health benefits include cardioprotective effects; chemopreventive properties; metabolic changes, such as improved glycemic control; protection from diabetic consequences; and synergistic therapeutic effects when administered with other treatment modalities.

Differential effects of long-term slow-pressor and subpressor angiotensin II on contractile and relaxant reactivity of resistance versus conductance arteries.

Vascular reactivity was evaluated in three separate arteries isolated from rats after angiotensin II (Ang II) was infused chronically in two separate experiments, one using a 14-day high, slow-pressor dose known to produce hypertension and the other using a 7-day low, subpressor but hypertensive-sensitizing dose. There were three new findings. First, there was no evidence of altered vascular reactivity in resistance arteries that might otherwise explain the hypertension due to the high Ang II or the hypertensive-sensitizing effect of the low Ang II dose.

Resveratrol can both enhance and relax adrenergic contractions of the rat tail artery.

Our aims were to determine 1) if resveratrol's vasorelaxant action is greater in the distal (resistance) versus proximal (conductance) portion of the rat tail artery, and 2) if it can be blocked by agents known to block different potassium (K) channels in arterial smooth muscle. We found that its half-maximally effective concentration values were essentially identical (25 ± 3 versus 27 ± 3 μM) for relaxing adrenergically-precontracted rings prepared from distal versus proximal tissues. This does not confirm a previous report of greater relaxation in resistance versus conductance arteries.

Sildenafil does not enhance but rather attenuates vasorelaxant effects of antidiabetic agents.

Type 2 diabetic men commonly experience erectile dysfunction for which phosphodiesterase-5 (PDE5) inhibitors like sildenafil (Viagra) are often recommended. By preventing degradation of cyclic guanosine monophosphate (cGMP) in vascular smooth muscle, these inhibitors also enhance arterial vasorelaxant effects of nitric oxide donors (which stimulate cGMP synthesis). In the present work, we confirmed this enhancing effect after co-administration of sildenafil with nitroprusside to freshly-isolated rat tail arterial tissues.

Chronic social isolation in the prairie vole induces endothelial dysfunction: implications for depression and cardiovascular disease.

Humans with depression show impaired endothelium-dependent vasodilation; one recent demonstration of which was in the form of a reduced acetylcholine (ACh)-induced relaxation of adrenergically-precontracted small arteries biopsied from older depressed patients. Results from such uses of ACh in general have been validated as the most predictive marker of endothelium-related cardiovascular diseases. Accordingly, we examined vascular reactivity to ACh in the socially isolated prairie vole, a new animal model relevant to human depression and cardiovascular disease.

Evidence of direct smooth muscle relaxant effects of the fibrate gemfibrozil.

Fibrates are commonly employed to treat abnormal lipid metabolism via their unique ability to stimulate peroxisome proliferator-activated receptor alpha (PPARalpha). Interestingly, they also decrease systemic arterial pressure, despite recent evidence that PPAR alpha may contribute to expression of renin and related hypertension. Yet, mechanisms responsible for their potential antihypertensive activity remain unresolved.

Exercise training normalizes enhanced glutamate-mediated sympathetic activation from the PVN in heart failure.

Exercise training (ExT) normalizes the increased sympathetic outflow in heart failure (HF), but the mechanisms are not known. We hypothesized that ExT would normalize the augmented glutamatergic mechanisms mediated by N-methyl-d-aspartic acid (NMDA) receptors within the paraventricular nucleus (PVN) that occur with HF. Four groups of rats were used: 1) sham-operated (Sham) sedentary (Sed), 2) Sham ExT, 3) HF Sed, and 4) HF ExT.

Chronic baroreceptor activation enhances survival in dogs with pacing-induced heart failure.

Much of the current pharmacological therapy for chronic heart failure targets neurohormonal activation. In spite of recent advances in drug therapy, the mortality rate for chronic heart failure remains high. Activation of the carotid baroreceptor (BR) reduces sympathetic outflow and augments vagal tone.

A novel method for the evaluation of proximal tubule epithelial cellular necrosis in the intact rat kidney using ethidium homodimer.

Background: Ethidium homodimer is a cell-membrane impermeant nuclear fluorochrome that has been widely used to identify necrotic cells in culture. Here, we describe a novel technique for evaluating necrosis of epithelial cells in the proximal tubule that involves perfusing ethidium homodimer through the intact rat kidney. As a positive control for inducing necrosis, rats were treated with 3.

Attenuation by 4-aminopyridine of delayed vasorelaxation by troglitazone.

Troglitazone and other thiazolidinediones (TZDs) are thought to relax arterial smooth muscle by directly inhibiting calcium channels in smooth muscle cell membranes. However, until recently such inhibition was only examined acutely, ie, within only seconds or minutes after administration of these agents to arterial smooth muscle preparations. Recently, a novel experiment was reported in which troglitazone caused a 2-phase relaxation of perfused resistance arteries, namely, an acute relaxation (within the first 20 minutes of treatment), which was blocked by a nonselective calcium channel blocker and a delayed relaxation (after 2 hours), which was not.

Simvastatin normalizes autonomic neural control in experimental heart failure.

Background: HMG-CoA reductase inhibitors (statins) have been shown to beneficially affect outcomes in chronic heart failure (CHF). We hypothesized that statins exert effects on autonomic function, as assessed by plasma norepinephrine levels, direct recordings of renal sympathetic nerve activity (RSNA), and baroreflex function.

Methods And Results: Normolipidemic CHF rabbits were treated with simvastatin or vehicle.