Abstract
[Purpose]To determine whether resveratrol improves the adverse effects age on vascular function in mesenteric arteries (MAs), and diminishes the hyperactivity in adrenal gland with age.[Methods]Male F344 x Brown Norway rats were assigned to 6-month control (YC), 6-month resveratrol (YR), 24-month control (OC) and 24-month resveratrol (OR). Resveratrol (15 mg/kg) was provided to resveratrol groups in drinking water for 14 days.[Results]Concentration response curves to phenylephrine (PE, 10-9-10-5M), acetylcholine (Ach, 10-9-10-5M) and resveratrol (10-8-10-4M) were evaluated in pressurized isolated MAs. The Ach concentration-response curve was right shifted with maximal response diminished in OC compared with YC rats. These effects were reversed by resveratrol treatment. The resveratrol-mediated relaxant responses were unchanged with age or resveratrol suggesting an endothelium-independent mechanism. Resveratrol tended to increase endothelial nitric oxide synthase; caused no effect on copper-zinc superoxide dismutase; and normalized the age-related elevatation in DβH and NPY levels in adrenal medulla, two indicators of sympathetic activity[Conclusion]These data indicate that resveratrol reverses age-related dysfunction in endothelium-dependent vasodilation in MAs and partially reverses hyperactivity of adrenomedullary function with age. This treatment may have a therapeuticpotential in the treatment of cardiovascular diseases or hypertension in the elderly.
Highlights
Aging is associated with phenotypic and functional changes in vascular structure and function and there is an age-related increase in the prevalence of hypertension, all of which elevate the risk for cardiovascular disease[1,2,3]
There was no change in sensitivity with resveratrol treatment, and maximal constriction with PE was similar in all four groups
This study indicates that age-related dysfunction inendothelium-dependent vasodilation in mesenteric arteries (MAs) can bereversed with resveratrol treatment
Summary
Aging is associated with phenotypic and functional changes in vascular structure and function and there is an age-related increase in the prevalence of hypertension, all of which elevate the risk for cardiovascular disease[1,2,3]. There is dysregulation of blood pressure, and the age-related increases in hypertension are associated with an increase in sympathetic nervous activity[12,13,14], and sustained elevation of catecholamine biosynthesizing enzymes in the adrenal medulla and peripheral sympathetic ganglia. Protein levels and enzyme activity of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis, are elevated in the adrenal medulla of senescent rats compared with younger animals[15,16,17,18].
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