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/minx1.73 m2 to 801+/-52, P<0.001, versus baseline) and glomerular filtration rate (115+/-7 mL/minx1.73 m2 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.
Montanari
Alberto
A
Dipartimento di Scienze Cliniche, Università di Parma, Via Gramsci 14, I-43100 Parma. montalbr@unipr.it
Biggi
Almerina
A
Carra
Nicoletta
N
Ziliotti
Maurizio
M
Fasoli
Elena
E
Musiari
Luisa
L
Perinotto
Patrizia
P
Novarini
Almerico
A
D000328:Adult; D000804:Angiotensin II / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D065128:Endothelin Receptor Antagonists; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D010456:Peptides, Cyclic / Q000494:pharmacology; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D065128:Endothelin Receptor Antagonists; D010456:Peptides, Cyclic; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; C072247:cyclo(Trp-Asp-Pro-Val-Leu)