A bradykinin antagonist abolishes beneficial effect of captopril on duration of survival after acute coronary artery ligation in hypertensive rats.
It has been recently suggested that bradykinin (BK) may act as a cardioprotective agent. In the present investigation, we evaluated the effects of captopril, an angiotensin-converting enzyme inhibitor (ACEI), and kinin B2 receptor antagonist, D-Arg-[Hyp3-D-Phe7]-BK, on the duration of survival after acute coronary artery ligation for 15 min in spontaneously hypertensive rats (SHR). The captopril treatment (16 and 32 ug/kg, i.v.) resulted in a significant (p < 0.05) increase in survival time of SHR as compared with saline-treated control SHR. Kinin B2 receptors antagonist (4 ug/kg, i.v.) pretreatment abolished (p > 0.05) the beneficial effect of captopril on survival time as compared to 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 as compared to the saline-treated control SHR. In addition, captopril administration caused a significant (p < 0.05) fall in the SBP, DBP and HR of SHR before ligation of the coronary artery (preligation). However, there was no significance (p > 0.05) in SBP, DBP and HR between saline- and kinin B2 receptor antagonist plus captopril-treated SHR during preligation. These finding might indicate that captopril possesses a cardioprotective property as demonstrated by increased in survival time of SHR. This beneficial effect of captopril is mediated via the kinin B2 receptor pathway because kinin B2 receptor antagonist pretreatment blocked the captopril-induced increase in survival time of SHR.
Sharma
Jagdish N
JN
Department of Applied Therapeutics, Faculty of Pharmacy, Health Sciences Center, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait. j.n.sharma@hsc.edu.kw
Abbas
S Atif
SA
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D065094:Bradykinin B2 Receptor Antagonists; D002216:Captopril / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000401:mortality* / Q000503:physiopathology; D008026:Ligation; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D015996:Survival Rate
D000806:Angiotensin-Converting Enzyme Inhibitors; D065094:Bradykinin B2 Receptor Antagonists; D002216:Captopril; C053010:NPC 567; D001920:Bradykinin