title: NO modulates myocardial O2 consumption in the nonhuman primate: an additional mechanism of action of amlodipine.
abstract: 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(-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 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.
authors.affiliation: Department of Physiology, New York Medical College, Valhalla, New York 10595, USA.
authors.forename: P R
authors.initials: PR
authors.lastname: Forfia
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.forename: D R
authors.initials: DR
authors.lastname: Knight
authors.forename: A H
authors.initials: AH
authors.lastname: Smith
authors.forename: C P
authors.initials: CP
authors.lastname: Doe
authors.forename: E A
authors.initials: EA
authors.lastname: Wolfgang
authors.forename: D M
authors.initials: DM
authors.lastname: Flynn
authors.forename: M S
authors.initials: MS
authors.lastname: Wolin
authors.forename: T H
authors.initials: TH
authors.lastname: Hintze
mesh_terms: D017311:Amlodipine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006439:Hemodynamics / Q000502:physiology; D066298:In Vitro Techniques; D008252:Macaca fascicularis; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology*; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D017257:Ramipril / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D026423:S-Nitroso-N-Acetylpenicillamine
chemical_list: D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D017311:Amlodipine; D009569:Nitric Oxide; C052549:ramiprilat; D026423:S-Nitroso-N-Acetylpenicillamine; D010396:Penicillamine; D017257:Ramipril; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester