Affiliation:
1. From the Department of Physiology, New York Medical College, Valhalla, NY (K.E.L, C.M.L.C., E.J.M., S.K.L., T.H.H.), and the Division of Hypertension and Vascular Research, Henry Ford Hospital, Detroit, Mich (E.G.S., O.A.C.).
Abstract
Abstract
—The aim of this study was to determine whether bradykinin, the angiotensin-converting enzyme inhibitor ramiprilat, and the calcium-channel antagonist amlodipine reduce myocardial oxygen consumption (MV̇
o
2
) via a B
2
-kinin receptor/nitric oxide–dependent mechanism. Left ventricular free wall and septum were isolated from normal and B
2
-kinin receptor knockout (B
2
−/−) mice. Myocardial tissue oxygen consumption was measured in an airtight chamber with a Clark-type oxygen electrode. Baseline MV̇
o
2
was not significantly different between normal (239±13 nmol of O
2
· min
−1
· g
−1
) and B
2
−/− (263±24 nmol of O
2
· min
−1
· g
−1
) mice. S-nitroso-
n
-acetyl-penicillamine (10
−7
to 10
−4
mol/L) reduced oxygen consumption in a concentration-dependent manner in both normal (maximum, 36±3%) and B
2
−/− mice (28±3%). This was also true for the endothelium-dependent vasodilator substance P (10
−10
to 10
−7
mol/L; 22±7% in normal mice and 20±4% in B
2
−/− mice). Bradykinin (10
−7
to 10
−4
mol/L), ramiprilat (10
−7
to 10
−4
mol/L), and amlodipine (10
−7
to 10
−5
mol/L) all caused concentration-dependent decreases in MV̇
o
2
in normal mice. At the highest concentration, tissue O
2
consumption was decreased by 18±3%, 20±5%, and 28±3%, respectively. The reduction in MV̇
o
2
to all 3 drugs was attenuated in the presence of N
G
-nitro-
l
-arginine-methyl ester. However, in the B
2
−/− mice, bradykinin, ramiprilat, and amlodipine had virtually no effect on MV̇
o
2
. Therefore, nitric oxide, through a bradykinin-receptor–dependent mechanism, regulates cardiac oxygen consumption. This physiological mechanism is absent in B
2
−/− mice and may be evidence of an important therapeutic mechanism of action of angiotensin-converting enzyme inhibitors and amlodipine.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Cited by
31 articles.
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