Endothelin-A receptors mediate renal hemodynamic effects of exogenous angiotensin II in humans

To investigate whether endothelin-A receptors mediate hemodynamic changes caused by exogenous Angiotensin II in humans, 7 healthy volunteers on a 250-mmol sodium diet underwent 3 separate p-aminohippurate and inulin-based renal hemodynamic studies. In 2 studies, Angiotensin II (increasing rates of 0.625, 1.25, and 2.5 ng/kg per minute, each for 30 minutes) was infused either alone or combined with endothelin-A blocker, BQ123, 0.4 nmol/kg per minute. A third infusion of BQ123 alone was not followed by any change. Angiotensin II infusion alone produced a progressive decrease in renal blood flow (1080 +/- 94 mL/min x 1.73 m(2) to 801 +/- 52, P < 0.001, versus baseline) and glomerular filtration rate (115 +/- 7 mL/min x 1.73 m(2) to 97 +/- 7, P < 0.001) with increase in filtration fraction (0.188 +/- .017 to 0.220 +/- .030, P < 0.01). Mean arterial pressure and renal vascular resistance increased markedly (86.8 +/- 3.1 to 97.5 +/- 4.4 mm Hg, P < 0.001 and 83 +/- 7 to 133 +/- 20 mm Hg/min per liter, P < 0.001, respectively). With Angiotensin II+BQ 123, mean arterial pressure still rose (86.2 +/- 3.1 to 91.1 +/- 4.3, P < 0.05 versus both baseline and BQ123 alone) but significantly less than with Angiotensin II alone (P < 0.05). Renal blood flow (1077 +/- 76 to 993 +/- 79, P < 0.001) and glomerular filtration rate (115 +/- 7 to 105 +/- 7, P < 0.05) also changed to a significantly lesser extent than with Angiotensin II alone (P < 0.05 for both), whereas filtration fraction remained unchanged (0.185 +/- .015 to 0.186 +/- .016). Renal vascular resistance rose only by 17% (82 +/- 5 to 95 +/- 9, P < 0.001 versus baseline as well as versus BQ123 or Angiotensin II alone). The results show that endothelin through Endothelin-A receptors contributes substantially to the systemic and renal vasoconstriction of low-dose exogenous Angiotensin II in healthy humans.