Renal vascular interaction of angiotensin II and prostaglandins in renovascular hypertension.
The vascular responses to angiotensin II (Ang II) in the renal circulation are increased in kidneys from rats with aortic coarctation compared with sham-operated rats. We have suggested that these differences are related to changes in mediators of the Ang II effect. The aim of this study was to investigate the role of arachidonic acid (AA) metabolites on the Ang II effect in the renal circulation of normotensive and hypertensive rats. We evaluated vascular renal reactivity in the rat isolated perfused kidney. Bolus injection of Ang II (9, 18, 36, 72 ng) increased perfusion pressure in a dose-dependent manner by 16.5+/-4, 23.5+/-4, 35.5+/-7, and 42.5+/-7 mm Hg in sham-operated rats and 50+/-6, 72+/-10, 92+/-6, and 120+/-6 mm Hg in rats with aortic coarctation. Ang II-induced vasoconstriction was prevented in hypertensive rats and potentiated in normotensive rats by the presence of indomethacin (1 microg/ml) in the perfusion solution. Furthermore, the use of the endoperoxide/thromboxane blocker (SQ29548, 1 microM) did not alter the effect of Ang II on the normotensive rats but prevented its effect in hypertensive rats. Moreover, the prostaglandin/ thromboxane (PGH2/TxA2) receptor agonist U46619 increased perfusion pressure to similar values in both kidneys from sham-operated or aortic coarctation rats. Ang II stimulated AA and prostaglandin release from isolated perfused kidneys. However, autacoid release was higher in kidneys from rats with aortic coarctation. In conclusion, we suggest that during the development of hypertension, the AA metabolism of vasoconstrictor prostaglandins is increased, and it mediates the vasoconstrictive effects of Ang II.
Department of Pharmacology and Toxicology, Centro de Investigación y de Estudios Avanzados del IPN, México, México.
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D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000758:Anesthesia; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000494:pharmacology; D006978:Hypertension, Renovascular / Q000473:pathology*; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects*; D010477:Perfusion; D011453:Prostaglandins / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D011453:Prostaglandins; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D016718:Arachidonic Acid; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C045749:SQ 29548; D007213:Indomethacin