ROLE OF ENDOTHELIUM IN ANGIOTENSIN-II FORMATION BY THE RAT AORTA AND MESENTERIC ARTERIAL BED

We investigated the angiotensin II (Ang II)-generating system by analy zing the vasoconstrictor effect of Ang II, angiotensin I (Ang I), and tetradecapeptide (TDP) renin substrate in the absence and presence of inhibitors of the renin-angiotensin system in isolated rat aortic ring s and mesenteric arterial beds with and without functional endothelium . Ang II, Ang I, and TDP elicited a dose-dependent vasoconstrictor eff ect in both vascular preparations that was completely blocked by the A ng II receptor antagonist saralasin (50 nM). The angiotensin convertin g enzyme (ACE) inhibitor captopril (36 mu M) completely inhibited the vasoconstrictor effect elicited by Ang I and TDP in aortic rings witho ut affecting that of Ang II. In contrast, captopril (36 mu M) signific antly reduced (80-90%) the response to bolus injection of Ang I, witho ut affecting those to Ang II and TDP in mesenteric arteries. Mechanica l removal of the endothelium greatly potentiated (70-95%) the vasocons trictor response to Ang II, Ang I, and TDP in aortic rings while these responses were unaffected by the removal of the endothelium of mesent eric arteries with sodium deoxycholate infusion. In addition, endothel ium disruption did not change the pattern of response elicited by thes e peptides in the presence of captopril. These findings indicate that the endothelium may not be essential for Ang II formation in rat mesen teric arteries and aorta, but it may modulate the response to Ang II. Although Ang II formation from Ang I is essentially dependent on ACE i n both vessels, our results suggest the existence of an alternative pa thway in the mesenteric arterial bed that may play an important role i n Ang II generation from TDP in resistance but not in large vessels du ring ACE inhibition.