Effects of long-term captopril treatment on endotheliumdependent relaxation in the spontaneously hypertensive rats (SHR)
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.
Keaton, A., While, C., & Berecek, K. (1996). Effects of long-term captopril treatment on endotheliumdependent relaxation in the spontaneously hypertensive rats (SHR). Retrieved from https://digitalcommons.pvamu.edu/medical-facpubs/74