NO modulates myocardial O2consumption in the nonhuman primate: an additional mechanism of action of amlodipine.

Recent evidence from our laboratory and others suggests that nitric oxide (NO) is a modulator of in vivo and in vitro oxygen consumption in the murine and canine heart. Therefore, the goal of our study was twofold: to determine whether NO modulates myocardial oxygen consumption 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 O2 electrode, we measured oxygen consumption in cynomologous monkey heart at baseline and after increasing doses of S-nitroso- N-acetylpenicillamine (SNAP; 10-7-10-4M), bradykinin (10-7-10-4M), ramiprilat (10-7-10-4M), and amlodipine (10-7-10-5M). SNAP (-38 ± 5.8%), bradykinin (-19 ± 3.9%), ramiprilat (-28 ± 2.3%), and amlodipine (-23 ± 4.5%) each caused significant ( P < 0.05) reductions in myocardial oxygen consumption at their highest dose. Preincubation of tissue with nitro-l-arginine methyl ester (10-4 M) blunted the effects of bradykinin (-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 myocardium in vitro, and they support a role for the calcium-channel blocker amlodipine as a modulator of myocardial oxygen consumption via a kinin-NO mediated mechanism.