title: Vascular responses to endothelin-1, angiotensin-II, and U46619 in glycerol-induced acute renal failure.
abstract: Angiotensin II and endothelin-1, major endogenous vasoconstrictors in acute renal failure (ARF), can modulate the effects of each other. This study aimed 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 (2.5-25 ng) caused an increase in perfusion pressure. Saralasin, 1 microM, a nonselective angiotensin receptor antagonist, reduced these responses by 61+/- 6% (p < 0.05). Surprisingly, SQ29548, 1 microM, a selective PGH2 /thromboxane A2 receptor blocker, also reduced angiotensin II responses (62 +/- 4%; p < 0.05). BQ610 1 microM, an ETA -selective receptor antagonist, was without effect, but BQ788 1 microM, an ETB -selective antagonist, attenuated the response by 70 +/- 4% (p < 0.05). In ARF, in contrast to angiotensin II, vasoconstriction by endothelin-1 (5-25 ng) was diminished. Saralasin further attenuated endothelin-1 response by 65 +/- 2% (p < 0.05), whereas SQ29548 was without effect. BQ788 reduced the responses by 67 +/- 7% (p < 0.05), whereas BQ610 was without effect (42 +/- 30%; p > 0.05). BQ610 and BQ788 combination further reduced vasoconstriction by 89 +/- 3% (p < 0.05). Responses to U46619 were not changed in ARF. However, saralasin and BQ788, but not BQ610, attenuated its vasoconstrictor action. We conclude that vascular responses in ARF may be attributed to enhanced responses to angiotensin II through activation of ETB and/or PGH2 /thromboxane A2 receptors. We also suggest that the vasoconstrictor response to endothelin-1 in ARF is predominantly ETB receptor-mediated.
authors.affiliation: Center for Cardiovascular Diseases, College of Pharmacy and Health Sciences, Texas Southern University, Houston, Texas, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Newaz
authors.forename: A O
authors.initials: AO
authors.lastname: Oyekan
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology*; D058186:Acute Kidney Injury / Q000139:chemically induced / Q000378:metabolism*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology*; D005990:Glycerol / Q000633:toxicity; D066298:In Vitro Techniques; D008297:Male; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D019332:Endothelin-1; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D005990:Glycerol