Resveratrol Treatment Reverses Mild Angiotensin II‐Induced Hypertension, but Not by Increased Natriuresis

Abstract

Resveratrol is a phenol that reduces blood pressure in animal models of hypertension, but a mechanism is unknown. We reported resveratrol is a renal vasodilator that increases nitric oxide bioavailability, and increases sodium excretion independent of its hemodynamic effects. Angiotensin II (AngII), a potent vasoconstrictor, also induces sodium retention. We hypothesized chronic resveratrol treatment may blunt AngII‐induced hypertension by its natriuretic effects. We infused male Sprague Dawley rats with vehicle or 80 μg AngII/day via osmotic minipumps over 4 weeks. Vehicle or AngII infused rats were individually housed, pair fed and placed on a diet of normal chow or chow plus 146 mg resveratrol/day. Groups included: 1) Control, 2) Resveratrol‐fed, 3) AngII‐treated, and 4) AngII plus Resveratrol. Systolic blood pressure (sBP) was measured by tail cuff plethsmography. During the 4th week rats were placed in metabolic caging for urine collection. AngII increased sBP in the first week by +14 ±5 mmHg (p<0.05) in group 3 and +10 ±3 mmHg (p<0.05) in the group 4, respectively. sBP was unchanged in groups 1 and 2. After 4 weeks, sBP remained elevated in group 3 rats with AngII, (+9 ±3 mmHg, p<0.05), but in group 4 with AngII plus Resveratrol, sBP was no longer elevated (+2 ±2 mmHg). We found no significant differences between groups in urine volume, sodium excretion or 7 day cumulative sodium balance (18.49 ±0.12, 17.75 ±0.16, 17.97±0.17, 18.46±0.18 mEq Na+/7 days in groups 1‐4 respectively). We conclude resveratrol did not blunt the initial pressor effect of Ang II, but sustained resveratrol ingestion reversed mild Ang II‐induced hypertension. The mechanism is not due to changes in sodium balance or volume status, and remains undefined.