Title

Effects of long-term captopril treatment on endotheliumdependent relaxation in the spontaneously hypertensive rats (SHR)

Document Type

Article

Publication Date

12-1-1996

Abstract

Genetic hypertension in the SHR is associated with endothelium dysfunction. The purpose of this study was to evaluate the effects of long-term treatment with captopril (ACE inhibitor) on endothelium dependent relaxation. Experimental male SHRs were divided into three groups: SHRCAP received oral captopril from in-utero to 6-7 months of age; OFFCAP were treated like SHRCAP but taken off captopril at 2 months of age and then maintained on tap water, and untreated SHR were given tap until experimentation. Age-matched WKYs were used as normotensive controls. The average MAP after 6 months of treatment with captopril were t23±3 mmHg (SHRCAP), as compared to 134±3 mmHg (OFFCAP), 169±3 mmHg (SHR), and 130±2 (WKY). Isolated aortic rings (2-3 mm) with functional endothelium were suspended in tissue chambers for measurement of isometric force. Indomethacin IbuM) treated rings were contracted by accumulative addition of phenylephnne (3x10° M - 3x 10° M). Acetylcholine-induced relaxation was markedly impaired in untreated SHRs. In contrast, endothelium dependent relaxation responses was significantly enhanced by captopril treatment. Maximum relaxation to acetylcholine was 8.6±5.61% of phenylephrine contraction in the SHRCAP group versus 35±8% in the untreated SHR (p<0.05). Additionally, EC50 values for acetylcholine-induced relaxation was significantly lower in SHRCAP 2 x 10° M versus SHR 107 M (p<0.05). Further, our data shows that 5 months after cessation of captopril treatment, aortic rings prepared from OFFCAP animals exhibited greater maximum acetylcholine-induced relaxation (11 ±9%) than that of the untreated SHRs (p<0.05). These data suggest that early application of captopril can prevent alterations in endothelial function observed in SHR even after ACE inhibitory therapy has been stopped.

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