© 1995 American Heart Association, Inc.
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Control of Carotid Vasomotor Tone by Local Renin–Angiotensin System in Normotensive and Spontaneously Hypertensive Rats
Role of Endothelium and Flow
From the Institut National de la Santé et de la Recherche Médicale (INSERM), Unit 141, IFR "Circulation Lariboisière," Paris, France.
Correspondence to Dr Bernard Lévy, INSERM Unit 141, Hôpital Lariboisière, 75010 Paris, France.
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. In contrast, AT1A increased diameters 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 larger in SHR than in WKY, which could participate in the relative insensitivity 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 local relaxing effect of ACE inhibition.
Key Words: ACE inhibitor • angiotensin AT1 receptor • flow • wall artery • in vitro isolated carotid artery
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