Endothelial NO formation does not control myocardial O2 consumption in mouse heart.
To test whether endothelium-derived nitric oxide (NO) regulates mitochondrial respiration, NO was pharmacologically modulated in isolated mouse hearts, which were perfused at constant flow to sensitively detect small changes in myocardial O2 consumption (MVO2). Stimulation of NO formation by 10 microM bradykinin (BK) increased coronary venous nitrite release fivefold to 58 +/- 33 nM (n = 17). Vasodilatation by BK, adenosine (1 microM), or papaverine (10 microM) decreased perfusion pressure, left ventricular developed pressure (LVDP), and MVO2. In the presence of adenosine-induced vasodilatation, stimulation of endothelial NO synthesis by BK had no effect on LVDP and MVO2. Also, inhibition of NO formation by NG-monomethyl-l-arginine (l-NMMA, 100 microM) did not significantly alter LVDP and MVO2. Similarly, intracoronary infusion of authentic NO <or=2 microM did not influence LVDP or MVO2 (-1 +/- 1%). Only when NO was >2 microM were contractile dysfunction and MVO2 reduction observed. Because BK-induced stimulation of endothelial NO formation and basal NO are not sufficient to impair MVO2 in the saline-perfused mouse heart, a tonic control of the respiratory chain by endothelial NO is difficult to conceive.
Kojic
Zvezdana Z
ZZ
Institut für Herz- und Kreislaufphysiologie, Heinrich-Heine-Universität Düsseldorf, Postfach 10 10 07, 40001 Düsseldorf, Germany.
Flogel
Ulrich
U
Schrader
Jurgen
J
Decking
Ulrich K M
UK
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects; D004730:Endothelium, Vascular / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D001920:Bradykinin