Tissue kallikrein increases duration of survival after prolonged coronary artery ligation in hypertensive rats.
There is evidence that the kallikrein-kinin system (KKS) is an important mediator in the regulation of blood pressure, and cardiac and renal hemodynamics. The present study was designed to examine the effect of tissue kallikrein and Trasylol, an inhibitor of tissue kallikrein, on survival time after continuous (prolonged) coronary artery ligation in spontaneously hypertensive rats (SHR). Tissue kallikrein (8 and 16 microg/kg, i.v.) treatment caused significant (p < 0.05) increases in the survival time of SHR as compared with the saline-treated control SHR. Trasylol pretreatment abolished (p < 0.05) the beneficial effect of tissue kallikrein on survival time. The tissue kallikrein treatment resulted in a significant (p < 0.05) reduction in systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) of SHR as compared to the saline-treated control SHR. Trasylol (6 microg/kg) treatment antagonized the effects of tissue kallikrein associated with survival time, SBP, DBP and HR. Ligation of the coronary artery caused a significant (p < 0.001) reduction in the SBP, DBP and HR of SHR, when the mean values were compared between before coronary artery ligation and after coronary artery ligation. However, there was no significant difference (p > 0.05) in SBP, DBP and HR between saline and kallikrein-treated SHR after coronary artery ligation. These findings may suggest that tissue kallikrein is able to act as a cardioprotective agent as demonstrated by an increase in survival time of SHR with prolonged coronary artery ligation.
Sharma
Jagdish N
JN
Department of Applied Therapeutics, Faculty of Pharmacy, Health Sciences Center, Kuwait University, Safat, Kuwait. j.n.sharma@hsc.kuniv.edu.kw
Abbas
S Atif
SA
Yusof
A P M
AP
Shah
Rajesh P
RP
Gan
Ee-Kiang
EK
D000818:Animals; D007611:Aprotinin / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D003327:Coronary Disease / Q000188:drug therapy* / Q000401:mortality; D006321:Heart / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology*; D007275:Injections, Intravenous; D007610:Kallikreins / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D008026:Ligation; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D015842:Serine Proteinase Inhibitors / Q000627:therapeutic use; D013534:Survival; D013997:Time Factors
D015842:Serine Proteinase Inhibitors; D007611:Aprotinin; D007610:Kallikreins