CONTROL OF CAROTID VASOMOTOR TONE BY LOCAL RENIN-ANGIOTENSIN SYSTEM IN NORMOTENSIVE AND SPONTANEOUSLY HYPERTENSIVE RATS - ROLE OF ENDOTHELIUM AND FLOW

To investigate the relation between the tissue renin-angiotensin syste m (RAS) and the local vasomotor tone of large arteries, we used in vit ro isolated carotid arteries from 14-week-old Wistar-Kyoto rats (WKY; n=80) and spontaneously hypertensive rats (SHR; n=80). Diameters were measured with the use of an ultrasonic echo-tracking system (12 MHz) u nder flow (2 mL/min) (F+) or no-flow (Fo) conditions, with intact endo thelium (Endo+) or after endothelium removal (Endo-). The role of tiss ue RAS was assessed by incubating isolated carotid arteries with an an giotensin-converting enzyme inhibitor (ACE I; lisinopril, 10(-6) mol/L ) or with a specific antagonist of angiotensin II AT, receptors (AT(1A ); losartan, 10(-6) mol/L). In addition, maximal dilation of carotid a rteries was measured after poisoning with KCN (100 mg/L). In all exper iments, KCN significantly increased carotid diameters (WKY, 23+/-0.9%; STIR, 19+/-0.8%; P<.001 versus control conditions). In intact carotid arteries, flow caused significant dilation in WKY (7+/-0.5%, P<.001) but had no effect in SHR. In the presence or absence of flow, ACE I an d AT(1A) induced similar dilations in both strains, and a specific ant agonist of bradykinin B-2 receptors (Hoe 140, 10(-7) mol/L) had no eff ect on ACE I-induced dilation. After endothelium removal, carotid arte ry diameters were significantly increased (P<.001) in both strains, al though more in SHR (13+/-0.8%) than in WKY (8+/-1.1%) (P<.001). Also, flow did not modify the diameter of deendothelialized vessels and ACE I had no effect in either strain. In contrast, AT(1A) increased diamet ers further (WKY, 4+/-0.4%; SHR, 3+/-0.6%; P<.01). The results of the present study suggest that in in vitro isolated intact carotid artery, (1) the endothelium exerts a basal vasoconstrictor effect that is lar ger in SHR than in WKY, which could participate in the relative insens itivity to flow in SHR; (2) in the absence of exogenous substrate the vessel wall is able to produce angiotensin II, which is active locally on the vascular tone; and (3) inhibition of angiotensin II formation, not degradation of bradykinin, appears to be responsible for the loca l relaxing effect of ACE inhibition.