Prevention of arterial structural alterations with verapamil and trandolapril and consequences for mechanical properties in spontaneously hypertensive rats

We compared the chronic effects in spontaneously hypertensive: rats (SHR) o f low doses of an angiotensin converting enzyme inhibitor, trandolapril, a Ca2+ channel antagonist, verapamil, and their combination (trandolapril-ver apamil), on arterial mechanical properties, arterial wall hypertrophy and e xtracellular matrix proteins. Four-week-old SHR were randomly allocated to oral treatment with verapamil (50 mg kg(-1) day(-1)), trandolapril (0.3 mg kg(-1) day(-1)), the combination of verapamil (50 mg kg(-1) day(-1)) plus t randolapril (0.3 mg kg(-1) day(-1)), or placebo for 4 months. A group of Wi star Kyoto (WKY) control rats received placebo for the same period of time. At the end of the treatment, mean blood pressure was lower in verapamil-tr andolapril than in trandolapril SHR, but remained higher than in WKY. Verap amil had no effects on blood pressure. Equivalent reduction in aortic wall hypertrophy was obtained in all treated SHR. Trandolapril and verapamil-tra ndolapril combination produced a significant reduction of aortic collagen d ensity compared with placebo SHR. Carotid total fibronectin, EIIIA fibronec tin isoform and alpha 5 beta 1 Integrin, were higher in the media of placeb o SHR than in WKY. EIIIA fibronectin isoform and alpha 5 beta 1 integrin we re reduced in verapamil-SHR compared with placebo-SHR and normalized in tra ndolapril and verapamil-trandolapril-SHR compared with WKY. SHR-placebo and SHR treated with either verapamil or trandolapril as single-drug treatment showed a 4-fold increase in total fibronectin compared to the WKY. Only SH R treated with vapamil-trandolapril combination had total fibronectin not s ignificantly different from that of WKY. Carotid arterial distensibility in creased only in verapamil-trandolapril treated rats. Multivariate analysis showed arterial distensibility to be negatively correlated to mean blood pr essure (P < 0.0001) and total fibronectin(P < 0.01). In conclusion, chronic treatment with the verapamil-trandolapril combination significantly improv ed in vivo arterial distensibility in SHR. The most important effects of th e combination on arterial mechanics compared to those of verapamil or trand olapril alone may have been the consequence of its stronger action on arter ial pressure, arterial wall hypertrophy and total fibronectin density. Howe ver we suggest that, in addition to the structural effects, complete normal ization of blood pressure is necessary to obtain normal arterial distensibi lity. (C) 1998 Elsevier Science B.V. All rights reserved.