Suppression of hypotensive responses of captopril and enalapril by the kallikrein inhibitor aprotinin in spontaneously hypertensive rats.
The present investigation evaluated the effects of aprotinin, an inhibitor of kallikrein, on blood pressure responses, heart rate, and duration of hypotension induced by acute administration of captopril and enalapril (angiotensin-converting enzyme inhibitors) in anaesthetized spontaneously hypertensive rats. Captopril (20 mg/kg) and enalapril (20 mg/kg) administered intravenously caused a significant (p < 0.001) fall in systolic and diastolic blood pressures in the absence of aprotinin. In contrast, captopril (20 mg/kg) and enalapril (20 mg/kg) failed (p > 0.05) to cause a fall in systolic and diastolic blood pressures in the presence of aprotinin (2 mg/kg). Captopril and enalapril were able to significantly reduce the heart rate (p < 0.05 and p < 0.001) in the presence as well as in the absence of aprotinin. The duration of hypotension produced by captopril and enalapril was abolished significantly (p < 0.001) in the presence of aprotinin. These findings may suggest that captopril and enalapril caused hypotension via the kallikrein pathway, since the kallikrein inhibitor aprotinin can antagonize the hypotensive responses of these agents. Thus, kallikrein may be an independent mediator in the regulation of blood pressure.
Sharma
J N
JN
Department of Pharmacology, School of Medical Sciences, University Sains Malaysia, Kelantan.
Amrah
S S
SS
Noor
A R
AR
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D007611:Aprotinin / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D002216:Captopril / Q000494:pharmacology*; D004656:Enalapril / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology; D007610:Kallikreins / Q000494:pharmacology; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR
D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril; D007611:Aprotinin; D002216:Captopril; D007610:Kallikreins