Pharmacological evidence for the existence of a local renin‐angiotensin system in porcine interlobar renal arteries

1 Changes in tension in response to cumulative additons of angiotensins (i.e., angiotensinogen, angiotensin I and angiotensin II), bradykinin and acetylcholine were monitored isometrically on ring preparations from porcine interlobar renal arteries. 2 Angiotensins consistently elicited contractile responses, whereas both bradykinin and acetylcholine produced relaxation of the arterial rings when active tone was induced by prostaglandin F 2α . 3 Contractile responses to angiotensin II could be completely blocked by the combined action of the cyclo‐oxygenase inhibitor, indomethacin (1 μ m ) and the lipoxygenase inhibitor, nordihydroguaiaretic acid (NDGA, 10 μ m ). 4 Relaxant responses to bradykinin were unchanged during blockade of thromboxane A 2 synthesis by dazoxiben (30μ m ) and proved to be largely resistant to blockade by indomethacin (1 μ m ) and the prostaglandin I 2 (prostacyclin) synthesis inhibitor, tranylcypromine (40 μ m ). 5 The angiotensin receptor blocker, saralasin (10 and 100 n m ) antagonized responses to angiotensinogen, angiotensin I and angiotensin II effectively and with similar potency. Enalaprilic acid, the active metabolite of the converting enzyme inhibitor enalapril (300 n m ), attenuated responses to angiotensin I but failed to inhibit those to angiotensinogen up to 1 μ m . The serine protease kallikrein (0.001 to 1 u ml −1 ) produced a dose‐dependent shift to the left of the concentration‐response curve for angiotensinogen. 6 It is suggested that the porcine interlobar renal artery possesses a local renin‐angiotensin system with activatable angiotensin II forming enzyme(s) within the vessel wall.