Arcuate Arteries

The role of cytochrome P-450 in the myogenic response of isolated, perfused renal arcuate arteries of dogs to elevations in transmural pressure was examined. The phospholipase A2 inhibitor oleyloxyethylphosphorylcholine (1 and 10 ,uM) inhibited the greater than threefold increase in active wall tension in these arteries after an elevation in perfusion pressure from 80 to 160 mm Hg. Inhibition of cyclooxygenase activity with indomethacin (1 or 10 ,uM) had no effect on this response. The cytochrome P-450 inhibitors ketoconazole (10 and 100 ,uM) and ,f-diethyl-aminoethyldiphenylpropylacetate (SKF 525A, 10 and 100 ,uM) also inhibited the myogenic response. At a pressure of 160 mm Hg, SKF 525A (10 jiM) and ketoconazole (100 ,uM) reduced active wall tension in renal arteries by approximately 70%. Partial inhibition of the myogenic response was obtained after perfusion of the vessels with mechanism-based inhibitors of P-450, 1-aminobenzotriazole (75 uM) and 12-hydroxy-16-heptadecynoic acid (20 ,uM). The thromboxane receptor antagonist SQ 29,548 (1 or 10 JIM) had no effect on the pressure-induced increase in active wall tension in renal arteries. Arachidonic acid (50 ,uM) constricted isolated perfused renal arteries and potentiated the myogenic response in the presence of indomethacin. This response was completely reversed by ketoconazole (100 ,uM) or SKF 525A (100 ,uM). Microsomes (1 mg/ml) prepared from small renal arteries (200-500 ,um) and incubated with [1-14C]arachidonic acid (0.5 ,uCi, 50 ,uM) produced a metabolite that coeluted with 20-hydroxyeicosatetraenoic acid (20-HETE) during reversed-phase high-perfor-