Effect of cyclooxygenase and thromboxane synthase inhibition on the response to angiotensin II in the hypoperfused canine kidney.
The potential for endogenous prostaglandin production to modulate the renal vascular response to intrarenal infusions of angiotensin II (AII) was investigated in the canine kidney at varying renal perfusion pressures (RPP), using suprarenal aortic constriction to vary RPP. AII, infused to achieve increments in renal arterial plasma concentrations of 300 pg/ml, induced reductions in renal blood flow (RBF) and glomerular filtration rate (GFR) when RPP was 80 mm Hg or above. When RPP was reduced to 60 mm Hg, AII decreased RBF, but GFR failed to change. The vasoconstrictor response to AII was enhanced by indomethacin (8 mg/kg) at all perfusion pressures, but was not modified by the thromboxane (Tx) A2 synthase inhibitor, UK 38,485 (1 mg/kg). In contrast, the lack of change in GFR in response to AII at a RPP of 60 mm Hg was converted to a significant reduction by both indomethacin and UK 38,485. These observations are consistent with the hypothesis that the effect of AII on RBF is attenuated by renal release of vasodilator prostaglandins at all RPP. However, at low RPP, AII infusion also induces the release a factor that increases GFR. As this response can be prevented by both TxA2 synthase and cyclooxygenase inhibition, it is possible that this factor is TxA2.
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D016861:Cyclooxygenase Inhibitors; D004285:Dogs; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects*; D011453:Prostaglandins / Q000096:biosynthesis; D012079:Renal Circulation / Q000187:drug effects; D013928:Thromboxane A2 / Q000096:biosynthesis; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D016861:Cyclooxygenase Inhibitors; D007093:Imidazoles; D011453:Prostaglandins; D000804:Angiotensin II; C039242:dazmegrel; D013928:Thromboxane A2; D013930:Thromboxane-A Synthase; D007213:Indomethacin