Recent studies suggest that endogenous endothelin mediates much of the vaso
constrictor activity and vascular fibrotic damage caused by chronic adminis
tration of angiotensin II. The present study uses the mixed endothelin-A an
d endothelin-B receptor antagonist bosentan and the endothelin-A-selective
blocker BQ-123 to study the contribution of endogenous endothelin to the pr
essor 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
mmHg, P <0.01, and 39 +/-4 mm Hg, P <0.005, respectively) while also incre
asing renal vascular resistance (4.3 +/-1 mm Hg/mL per min, P <0.001, and 1
0 +/-1 mm Hg/mL per min, P <0.001, respectively). In the presence of bosent
an, 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-1
23 were similar. In contrast, these parameters were unaffected during high-
dose angiotensin II infusion+bosentan, although BQ-123 did selectively redu
ce the rise in renal vascular resistance, possibly via an endothelin B-medi
ated nitric oxide effect. In contrast, high-dose angiotensin II caused natr
iuretic and diuretic effects that were completely prevented by bosentan. Th
ese results show that endothelin (via endothelin A) contributes to the pres
sor and renal vasoconstrictor actions of acutely administered low-dose angi
otensin 11. Furthermore, our data suggest that the previously described ang
iotensin II-induced natriuresis and diuresis observed with a high pressor d
ose of angiotensin II is mediated by endothelin.