title: 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)
authors.affiliation: Institut National de la Santé et de la Recherche Médicale INSERM, Unit 141, IFR Circulation Lariboisière, Paris, France.
authors.forename: L
authors.initials: L
authors.lastname: Caputo
authors.forename: A
authors.initials: A
authors.lastname: Tedgui
authors.forename: B I
authors.initials: BI
authors.lastname: Lévy
mesh_terms: D000704:Analysis of Variance; D000804:Angiotensin II / Q000037:antagonists & inhibitors; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D002339:Carotid Arteries / Q000187:drug effects / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D006973:Hypertension / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D017706:Lisinopril / Q000494:pharmacology; D019808:Losartan; D010477:Perfusion; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology; D014159:Transducers; D014666:Vasomotor System / Q000187:drug effects / Q000502:physiology*
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; D017706:Lisinopril; D019808:Losartan