Coronary vasodilator responses to bradykinin in euglycemic and diabetic rats.
Diabetes mellitus is associated with endothelial dysfunction that is believed to result in impaired release of vasoconstrictor and vasodilator substances from the endothelium and thereby diminished reactivity of many vascular beds. This study was designed to characterize bradykinin (BK)-induced coronary vasodilation in normal and diabetic rats. Bradykinin-stimulated vasodilation of the rat coronary vasculature is mediated by a cytochrome P450-1A (CYP-1A)- inhibitable metabolite that activates KCa, but not KATP, channels on the coronary vascular smooth muscle. Although BK stimulates the release of nitric oxide from the vascular endothelium, the released nitric oxide and its ability to stimulate guanylate cyclase only modulates the duration of, rather than the magnitude of, BK-induced coronary vasodilation. Twelve weeks of streptozotocin-induced diabetes did not affect the coronary vascular responses to BK or the components that mediate BK-induced vasodilation (ie, K-channel activation, nitric oxide-guanylate cyclase). The data support the conclusions that the coronary vasodilator response of the rat to BK is CYP-1A and KCa-channel mediated, that coreleased nitric oxide only modulates the duration of BK-induced vasodilation, and that these mechanisms are unaffected by moderate diabetes.
Given
M B
MB
Department of Medicine, Louisiana State University Medical Center, New Orleans,  USA.
Greenberg
S S
SS
Giles
T D
TD
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000503:physiopathology*; D004195:Disease Models, Animal; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin / Q000009:adverse effects; D014664:Vasodilation / Q000187:drug effects*
D009569:Nitric Oxide; D013311:Streptozocin; D001920:Bradykinin