Endothelin mediates some of the renal actions of acutely administered angiotensin II.
Recent studies suggest that endogenous endothelin mediates much of the vasoconstrictor activity and vascular fibrotic damage caused by chronic administration of angiotensin II. The present study uses the mixed endothelin-A and endothelin-B receptor antagonist bosentan and the endothelin-A-selective blocker BQ-123 to study the contribution of endogenous endothelin to the pressor and renal action of acutely administered angiotensin II in conscious, chronically catheterized rats. Exposure to angiotensin II at 0.48 pmol 0.5 ng/100 g body weight per min IV (low dose) and 1.91 pmol 2.0 ng/100 g body weight per min IV (high dose) raised mean arterial blood pressure (18+/-4 mm Hg, P<0.01, and 39+/-4 mm Hg, P<0.005, respectively) while also increasing renal vascular resistance (4.3+/-1 mm Hg/mL per min, P<0.001, and 10+/-1 mm Hg/mL per min, P<0.001, respectively). In the presence of bosentan, pressor and renal vasoconstrictor responses to low-dose angiotensin II were blunted (P<0.02 and P<0.01, respectively), and the results with BQ-123 were similar. In contrast, these parameters were unaffected during high-dose angiotensin II infusion+bosentan, although BQ-123 did selectively reduce the rise in renal vascular resistance, possibly via an endothelin B-mediated nitric oxide effect. In contrast, high-dose angiotensin II caused natriuretic and diuretic effects that were completely prevented by bosentan. These results show that endothelin (via endothelin A) contributes to the pressor and renal vasoconstrictor actions of acutely administered low-dose angiotensin II. Furthermore, our data suggest that the previously described angiotensin II-induced natriuresis and diuresis observed with a high pressor dose of angiotensin II is mediated by endothelin.
Riggleman
A
A
Department of Physiology, Division of Exercise Physiology, West Virginia University, Morgantown 26506-9229, USA.
Harvey
J
J
Baylis
C
C
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D000077300:Bosentan; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000502:physiology*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D007677:Kidney Function Tests; D008297:Male; D010456:Peptides, Cyclic / Q000494:pharmacology; D011311:Pressoreceptors / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D013449:Sulfonamides / Q000494:pharmacology
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D010456:Peptides, Cyclic; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D013449:Sulfonamides; D000804:Angiotensin II; D000077300:Bosentan; C072247:cyclo(Trp-Asp-Pro-Val-Leu)