Effects of renal arterial endothelin-1 and endogenous endothelins on regional kidney blood flow and banal antihypertensive mechanisms in anesthetizedrabbits

To determine how endothelins affect regional kidney blood flow and response s to increased renal artery pressure (RAP), an extracorporeal circuit was e stablished to control RAP independent of the mean systemic arterial pressur e (MAP). RAP was first set at - 65 mm Hg, and endothelin-l (1 ng/kg/min for 30 min then 0.4 ng/kg/min) or vehicle was infused into the renal artery, o r the ETA/ETB antagonist TAK-044 (3 mg/kg plus 3 mg/kg/h) or vehicle was ad ministered intravenously. RAP was then progressively increased in steps fro m similar to 65 to similar to 160 mm Hg. When RAP was similar to 65 mm Hg, endothelin-1 increased renal vascular resistance (RVR, 72%), and reduced co rtical (CBF, 26%) but not medullary blood flow (MBF). TAK 044 reduced MAP ( 12%) and RVR (15%) and increased CBF (21%) but not MBF. When RAP was increa sed, renal blood flow (RBF), glomerular filtration rate, and urine and sodi um excretion increased, while MAP fell. These responses were unaffected by endothelin-l. TAK-044 potentiated the increases in RBF and reductions in MA P in response to increased RAP, but did not affect urine and sodium excreti on. Plasma renin activity was reduced by endothelin-l and increased by TAK- 044. Thus, both exogenous and endogenous endothelins reduce CBF but not MBF , and reduce plasma renin activity, but neither affect pressure natriuresis , Copyright (C) 2000 S. Karger AG, Basel.