Vascular responses to endothelin-1, angiotensin-II, and U46619 in glycerol-induced acute renal failure

Angiotensin II and endothelin-1, major endogenous vasoconstrictors in acute renal failure (ARF), can modulate the effects of each other. This study ai med to evaluate the interaction between these vasoconstrictors in glycerol- induced ARF by evaluating their effects in the isolated perfused kidney in the presence of their respective antagonists. In ARF, angiotensin II (2.5-2 5 ng) caused an increase in perfusion pressure. Saralasin, 1 muM, a nonsele ctive angiotensin receptor antagonist, reduced these responses by 61 +/- 6% (p < 0.05). Surprisingly. SQ29548, 1 <mu>M, a selective PGH(2)/thromboxane A(2) receptor blocker, also reduced angiotensin II responses (62 +/- 4%; p < 0.05). BQ610 1 <mu>M, an ETA-selective receptor antagonist, was without effect, but BQ788 1 muM, an ETB-selective antagonist, attenuated the respon se by 70 +/- 4% (p < 0.05). In ARE in contrast to angiotensin II, vasoconst riction by endothelin-1 (5-25 ng) was diminished. Saralasin further attenua ted endothelin-1 response by 65 +/- 2% (p < 0.05), whereas SQ29548 was with out effect. BQ788 reduced the responses by 67 +/- 7% (p < 0.05), whereas BQ 610 was without effect (42 +/- 30%; p > 0.05). BQ610 and BQ788 combination further reduced vasoconstriction by 89 +/- 3% (p < 0.05). Responses to U466 19 were not changed in ARF. However, saralasin and BQ788, but not BQ610, at tenuated its vasoconstrictor action. We conclude that vascular responses in ARF may be attributed to enhanced responses to angiotensin II through acti vation of ETB and/or PGH(2)/thromboxane A(2) receptors. We also suggest tha t the vasoconstrictor response to endothelin-1 in ARF is predominantly ETB receptor-mediated.