Endothelin-A Receptors Mediate Renal Hemodynamic Effects of Exogenous Angiotensin II in Humans

Abstract

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×1.73 m 2 to 801±52, P <0.001, versus baseline) and glomerular filtration rate (115±7 mL/min×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.