NO modulates myocardial O-2 consumption in the nonhuman primate: an additional mechanism of action of amlodipine

NO modulates myocardial O-2 consumption in the nonhuman primate: an additio nal mechanism of action of amlodipine. Am. J. Physiol. 276 (Heart Circ. Phy siol. 45): H2069-R2075, 1999.-Recent evidence from our laboratory and other s suggests that nitric oxide (NO)is a modulator of in vivo and in vitro oxy gen consumption in the murine and canine heart. Therefore, the goal of our study was twofold: to determine whether NO modulates myocardial oxygen cons umption in the nonhuman primate heart in vitro and to evaluate whether the seemingly cardioprotective actions of amlodipine may involve an NO-mediated mechanism. Using a Clark-type O-2 electrode, we measured oxygen consumptio n in cynomologous monkey heart at baseline and after increasing doses of S- nitroso-N-acetylpenicillamine (SNAP; 10(-7)-10(-4) M), bradykinin (10-7-10- 4 M), ramiprilat (10(-7)-10(-4) M), and amlodipine (10(-7)-10(-5) M). SNAP (-38 +/- 5.8%), bradykinin (-19 +/- 3.9%), ramiprilat (-28 +/- 2.3%), and a mlodipine (-23 +/- 4.5%) each caused significant (P < 0.05) reductions in m yocardial oxygen consumption at their highest dose. Preincubation of tissue with nitro-L-arginine methyl ester (10(-4) M) blunted the effects of brady kinin (-5.4 +/- 3.2%), ramiprilat (-4.8 +/- 5.0%), and amlodipine (-5.3 +/- 5.0%) but had no effect on the tissue response to SNAP (-38 +/- 5.8%). Our results indicate that NO can reduce oxygen consumption in the primate myoc ardium in vitro, and they support a role for the calcium-channel blocker am lodipine as a modulator of myocardial oxygen consumption via a kinin-NO med iated mechanism.