title: Impaired nitric oxide modulation of myocardial oxygen consumption in genetically cardiomyopathic hamsters.
abstract: We investigated the role of kinin and nitric oxide (NO) in the modulation of cardiac O(2)consumption in Syrian hamsters with overt heart failure (HF) and age-matched normal hamsters. Using echocardiography, the hamsters with heart failure had reduced ejection fraction [31(+/-8) v 76(+/-5)%] and LV dilation [4.9(+/-0. 2) v 5.7(+/-0.3) mm, both P<0.05 from normal]. O(2)consumption in the left ventricular free wall was measured using a Clark-type O(2)electrode in an air-tight chamber, containing Krebs solution buffered with Hepes (37 degrees C, pH 7.4). Concentration response curves to bradykinin (BK), ramiprilat (RAM), amlodipine (AMLO) and the NO donor, S -nitroso- N -acetyl-penicillamine (SNAP) were performed. Basal myocardial O(2)consumption was lower in the HF group compared to normal [316(+/-21) v 404(+/-36) nmol O(2)/min/g, respectively, P<0.05]. In the hearts from normal hamsters BK (10(-4)mol/l), RAM (10(-4)mol/l), and AMLO (10(-5)mol/l) all significantly reduced myocardial O(2)consumption by 42(+/-6)%, 29(+/-7)% and 27(+/-5)% respectively. This reduction was attenuated in the presence of N -nitro- l -arginine methyl ester (l -NAME) [BK: 3.3(+/-1.5)%, RAM: 3.3(+/-1.2)%, AMLO: 2.3(+/-1.2)%, P<0.05]. Interestingly in the hearts from HF group, BK, RAM and AMLO caused a significantly smaller reduction in myocardial O(2)consumption [10(+/-2)%, 2.5(+/-1.3)%, 6.3(+/-2.3)%, P<0.05]. In contrast, the NO donor SNAP reduced myocardial O(2)consumption in both groups and all those responses were not affected by l -NAME. These data indicate that endogenous NO production through the kinin-dependent mechanism is impaired at end-stage heart failure. The loss of kinin and NO control of mitochondrial respiration may contribute to the pathogenesis of heart failure.
authors: Department of Physiology, New York Medical College, Valhalla, NY 10595, USA.
authors: K E
authors: KE
authors: Loke
authors: E J
authors: EJ
authors: Messina
authors: S
authors: S
authors: Mital
authors: T H
authors: TH
authors: Hintze
mesh_terms: D017311:Amlodipine / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology; D009202:Cardiomyopathies / Q000235:genetics* / Q000378:metabolism*; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004452:Echocardiography; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007705:Kinins / Q000502:physiology; D008297:Male; D008647:Mesocricetus; D009132:Muscles / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D010100:Oxygen / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D017257:Ramipril / Q000031:analogs & derivatives* / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D004791:Enzyme Inhibitors; D007705:Kinins; D020030:Nitric Oxide Donors; C110881:S-nitro-N-acetylpenicillamine; D014665:Vasodilator Agents; D017311:Amlodipine; D009569:Nitric Oxide; C052549:ramiprilat; D010396:Penicillamine; D017257:Ramipril; D010100:Oxygen; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester