The role of nitric oxide in bradykinin-induced dilation of coronary resistance vessels in patients with hypercholesterolemia.
OBJECTIVE
In hypercholesterolemic patients, acetylcholine- and substance P-mediated endothelium-dependent dilation of the coronary resistance vessels is impaired due to decreased nitric oxide production. However, it is not clear if bradykinin-induced coronary vasodilation is impaired in these patients. We investigated whether the endothelium-dependent dilation of coronary resistance vessels mediated by bradykinin is impaired in patients with hypercholesterolemia and, if so, whether this impairment is caused by a decreased production of nitric oxide.


METHODS
We examined the coronary vascular responses to acetylcholine and bradykinin. The vascular responses to bradykinin were also assessed after N(G)-monomethyl-L-arginine was infused to inhibit nitric oxide production. Drugs were infused into the left coronary ostium and coronary blood flow (CBF) and coronary vascular resistance were evaluated by quantitative angiography and Doppler flow velocity measurements.


METHODS
Twelve hypercholesterolemic patients and 11 control patients with angiographically normal coronary arteries were studied.


RESULTS
The vasodilator responses to acetylcholine and bradykinin were reduced in hypercholesterolemic patients compared with control patients (p<0.005 and p<0.04, respectively, by two-way analysis of variance (ANOVA)). The CBF responses to acetylcholine and bradykinin were significantly correlated (r=0.56; p<0.01). Bradykinin-induced dilation was similar in hypercholesterolemic patients and control patients after inhibition of nitric oxide.


CONCLUSIONS
These results suggest that the bradykinin-mediated endothelium-dependent dilation of coronary resistance vessels may be impaired due to depressed nitric oxide production in patients with hypercholesterolemia.
First Department of Internal Medicine, Hiroshima University School of Medicine, Shobara.
M
M
Kato
N
N
Shiode
H
H
Teragawa
H
H
Hirao
T
T
Yamada
T
T
Yamagata
H
H
Matsuura
G
G
Kajiyama
D000109:Acetylcholine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D001783:Blood Flow Velocity; D001920:Bradykinin / Q000494:pharmacology*; D003331:Coronary Vessels / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D006937:Hypercholesterolemia / Q000503:physiopathology*; D007261:Infusions, Intra-Arterial; D017078:Laser-Doppler Flowmetry; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D014664:Vasodilation / Q000187:drug effects*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000241:Adenosine; D000109:Acetylcholine; D001920:Bradykinin