Chronic hydralazine treatment alters the acute pressure–natriuresis curve in young spontaneously hypertensive rats

Abstract

The pressure-natriuresis relationship was studied in anesthetized, 7- to 9-week-old control spontaneously hypertensive rats (SHR) and in SHR that had been treated with hydralazine (20 mg.kg-1.day-1 in drinking water) starting at 4-5 weeks of age. To minimize reflex changes in kidney function during changes in renal artery pressure, neural and hormonal influences on the kidney were fixed by surgical renal denervation, adrenalectomy, and infusion of a hormone cocktail (330 microL.kg-1.mikn-1) containing high levels of aldosterone, arginine vasopressin, hydrocortisone, and norepinephrine dissolved in 0.9% NaCl containing 1% albumin. Changes in renal function were measured using standard clearance techniques, while renal artery pressure was varied between 136 +/- 1 and 186 +/- 2 mmHg (1 mmHg = 133.32 Pa) in control SHR (n = 10) and between 113 +/- 1 and 162 +/- 2 mmHg in treated SHR (n = 11). Mean arterial pressure (+/- SE) under Inactin anesthesia was 172 +/- 3 mmHg in control SHR and 146 +/- 3 mmHg in treated SHR (p less than 0.05). Where renal artery pressure overlapped between groups, there were no significant differences in glomerular filtration rate. Renal blood flow was also similar in both groups, although at 160 mmHg blood flow was slightly but significantly reduced in treated SHR. Urine flow and total and fractional sodium excretion increased similarly with increases in renal artery pressure in both groups, but the pressure-natriuresis curve in hydralazine-treated SHR was displaced to the left along the pressure axis. The data indicate that chronic administration of hydralazine in young SHR enhances fractional sodium excretion, suggesting that tubular reabsorption of sodium is decreased by hydralazine.