Trandolapril treatment at low dose improves mechanical and functional properties in perfused coronary arteries of spontaneously hypertensive rat.
The ex-vivo effects of a 1-month treatment period with trandolapril at a low dose (0.3 mg/kg/day) were assessed on the mechanical and functional alterations observed in SHR coronary arteries. The in-vitro intrinsic elastic properties of the wall in treated SHR coronary arteries were determined in comparison to those of SHR rats. In preconstricted preparations, agonist- and flow-induced dilatations were investigated in arteries of both groups. Arterial segments were cannulated at both ends using an arteriograph system. Internal diameter and wall thickness were continuously monitored while intraluminal pressure and flow were controlled. Wall thickness was reduced in arteries of treated rats compared to those in control SHR (mm): 52 +/- 2 vs. 41 +/- 2, P < 0.001, respectively. Arterial stiffness, expressed by the incremental elastic modulus-stress relationship, was significantly lower in arteries of treated compared to control SHRs. In preconstricted preparations, dilatations induced by bradykinin were significantly greater in treated SHR compared to control SHR arteries whereas dilatations induced by acetylcholine were slightly but not significantly increased. On the other hand, starting flow at the plateau of 5-HT-induced constriction led to dilatations which were not significantly different in the treated compared to the control group. The maximal dilatation induced by flow in arteries of treated rats was obtained for the same value of shear stress compared to that determined in preparations of control SHRs: (dyn/cm2) 63 +/- 3 vs. 61 +/- 2, respectively, NS. These results show that together with hypertrophy, the abnormal mechanical properties observed in the coronary arterial wall of SHR were improved by a low dose of trandolapril treatment. However, differential effects of trandolapril treatment were observed on agonist and flow-induced dilatations. Although flow-induced dilatation seemed to remain unaffected, acetylcholine-induced dilatation was slightly improved and bradykinin-induced dilatation was markedly increased by trandolapril treatment.
Department of Pharmacology, Faculty of Pharmacy, University Victor-Segalen Bordeaux II, France.
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Pourageaud
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Hamon
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Freslon
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001920:Bradykinin / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects*; D006973:Hypertension / Q000188:drug therapy*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D010477:Perfusion; D051381:Rats; D011918:Rats, Inbred SHR; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D000959:Antihypertensive Agents; D007211:Indoles; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C052035:trandolapril; D000109:Acetylcholine; D001920:Bradykinin