Sustained resveratrol infusion increases natriuresis independent of renal vasodilation

Abstract

Resveratrol is reported to exert cardio-renal protective effects in animal models of pathology, yet the mechanisms underlying these effects are poorly understood. Previously, we reported an i.v. bolus of resveratrol induces renal vasodilation by increasing nitric oxide bioavailability and inhibiting reactive oxygen species. Thus, we hypothesized a sustained infusion of resveratrol would also increase renal blood flow (RBF), and additionally glomerular filtration rate (GFR). We infused vehicle for 30 min followed by 30 min resveratrol at either: 0, 0.5, 1.0, 1.5 mg/min, and measured RBF, renal vascular resistance (RVR), GFR, and urinary sodium excretion. At all three doses, blood pressure and GFR remained unchanged. Control RBF was 7.69 ± 0.84 mL/min/gkw and remained unchanged by 0.5 mg/min resveratrol (7.88 ± 0.94 mL/min/gkw, n = 9), but urinary sodium excretion increased from 2.19 ± 1.1 to 5.07 ± 0.92 μmol/min/gkw (n = 7, P < 0.01). In separate experiments, 1.0 mg/min resveratrol increased RBF by 17%, from 7.16 ± 0.29 to 8.35 ± 0.42 mL/min/gkw (P < 0.01, n = 10), decreased RVR 16% from 13.63 ± 0.65 to 11.36 ± 0.75 ARU (P < 0.003) and increased sodium excretion from 1.57 ± 0.46 to 3.10 ± 0.80 μmol/min/gkw (n = 7, P < 0.04). At the 1.5 mg/min dose, resveratrol increased RBF 12% from 6.76 ± 0.57 to 7.58 ± 0.60 mL/min/gkw (n = 8, P < 0.003), decreased RVR 15% (15.58 ± 1.35 to 13.27 ± 1.14 ARU, P < 0.003) and increased sodium excretion (3.99 ± 1.71 to 7.80 ± 1.51 μmol/min/gkw, n = 8, P < 0.04). We conclude that a constant infusion of resveratrol can induce significant renal vasodilation while not altering GFR or blood pressure. Also, resveratrol infusion produced significant natriuresis at all doses, suggesting it may have a direct effect on renal tubular sodium handling independent of renal perfusion pressure or flow.

Keywords: Glomerular filtration; natriuresis; nitric oxide; renal blood flow.

Figure 1.

Mean arterial pressure (MAP) with intravenous vehicle (30 min) followed by resveratrol (Resv.) infusion (30 min) in three different groups (n = 7, 10, and 7, respectively) at three different doses. Resveratrol infusion had no effect on MAP.

Figure 2.

Renal blood flow (RBF) in response to vehicle (30 min) followed by resveratrol (Resv.) infusion (30 min). The lower dose of 0.5 mg/min had no effect on RBF, but both higher doses increased RBF by 17% and 12%, respectively.

Figure 3.

Renal vascular resistance (RVR) in response to vehicle (30 min) followed by resveratrol (Resv.) infusion (30 min). The lower dose of 0.5 mg/min had no effect on RVR, but both higher doses decreased RVR by 16% and 15%, respectively.

Figure 4.

Glomerular Filtration Rate (GFR) during vehicle (30 min) followed by resveratrol (Resv.) infusion (30 min). Resveratrol infusion had no effect on GFR at any dose.

Figure 5.

Urine Flow Rate in response to vehicle (30 min) followed by resveratrol (Resv.) infusion (30 min). Resveratrol infusion rate increased urine flow in all three groups by 59%, 103%, and 71%, respectively.

Figure 6.

Urinary sodium excretion in response to vehicle (30 min) and resveratrol (Resv.) infusion (30 min). All three doses of resveratrol infusion increased sodium excretion, by 132%, 97%, and 95%, respectively.