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Methods and findings in experimental and clinical pharmacology

Effect of captopril in the presence of kinin B2 receptor antagonist on duration of survival after prolonged coronary artery ligation in hypertensive rats.


PMID 16801982

Abstract

In the present investigation, we evaluated the potential effects of captopril, an angiotensin-converting enzyme inhibitor, in the absence and presence of kinin B(2) receptor antagonist (D-Arg-[Hyp3-D-Phe7]-BK) on the duration of survival after prolonged coronary artery ligation in spontaneously hypertensive rats (SHR). The captopril treatment (16 and 32 microg/kg; i.v.) resulted in a significant (p < 0.05) increase in survival time of SHR when compared with that of saline-treated control SHR. Kinin B(2) receptor antagonist (4 microg/kg; i.v.) pretreatment abolished (p > 0.05) the beneficial effect of captopril on the survival time when compared with that in saline-treated control SHR. Both the ligation of coronary artery and captopril treatment resulted in a significant (p < 0.001) fall in systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) of SHR when compared with those of the saline-treated control SHR. In addition, captopril administration caused a significant (p < 0.05) fall in SBP, DBP, and HR of SHR before ligation of the coronary artery (preligation). However, there was no significant change (p > 0.05) in SBP, DBP, and HR between saline- and kinin B(2) receptor antagonist plus captopril-treated SHR during preligation. These finding might indicate that captopril possesses a cardioprotective property as demonstrated by an increase in the survival time of SHR. This beneficial effect of captopril is mediated via the kinin B(2) receptor pathway because kinin B(2) receptor antagonist pretreatment blocked the captopril-induced increase in the survival time of SHR.