Control of carotid vasomotor tone by local renin-angiotensin system in normotensive and spontaneously hypertensive rats. Role of endothelium and flow

Abstract

To investigate the relation between the tissue renin-angiotensin system (RAS) and the local vasomotor tone of large arteries, we used in vitro 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) under flow (2 mL/min) (F+) or no-flow (Fo) conditions, with intact endothelium (Endo+) or after endothelium removal (Endo-). The role of tissue RAS was assessed by incubating isolated carotid arteries with an angiotensin-converting enzyme inhibitor (ACE I; lisinopril, 10(-6) mol/L) or with a specific antagonist of angiotensin II AT1 receptors (AT1A; losartan, 10(-6) mol/L). In addition, maximal dilation of carotid arteries was measured after poisoning with KCN (100 mg/L). In all experiments, KCN significantly increased carotid diameters (WKY, 23 +/- 0.9%; SHR, 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 and AT1A induced similar dilations in both strains, and a specific antagonist of bradykinin B2 receptors (Hoe 140, 10(-7) mol/L) had no effect on ACE I-induced dilation. After endothelium removal, carotid artery diameters were significantly increased (P < .001) in both strains, although 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.(ABSTRACT TRUNCATED AT 250 WORDS)