Role of cellular acidosis in production of nitric oxide in canine ischemic myocardium.

Abstract

We tested the hypothesis that cellular acidosis modulates the production of nitric oxide (NO) in ischemic hearts. In canine hearts, we decreased coronary blood flow (CBF) to one third of the control by reduction of coronary perfusion pressure (105+/-3 to 41+/-5 mmHg), and thereafter we maintained CBF constant (89.8+/-1.6 to 30.0+/-0.5 ml/100 g/min) with an intracoronary administration of either saline, atropine, rauwolscine, HOE140, 8-sulfophenyltheophylline (8SPT), NaHCO3, or HOE642 (the inhibitor of Na+/H+ exchange). The cardiac NO levels defined as the differences of the nitrate and nitrite levels between coronary venous and arterial blood increased in the saline administration (2.9+/-0.2 to 12.7+/-1.7 micromol/l), and the extents of increases were identical in the condition of either saline, atropine, rauwolscine, HOE140 or 8SPT administration. In the condition with either NaHCO3 or HOE642, the increases in the cardiac NO levels were blunted (4.5+/-0.7 and 4.8+/-0.4 micromol/l, respectively). Cyclic GMP content of epicardial coronary artery in the ischemic area increased, which was also attenuated by either NaHCO3 or HOE642. We confirmed the acidosis-induced NO production in a more severe ischemic myocardium, and also showed that cellular acidosis produced by infusion of HCl increased NO production in non-ischemic myocardium. We conclude that cellular acidosis and subsequent activation of Na+/H+ exchanges modulate production of endogenous NO in canine ischemic myocardium.

• Authors: M Kitakaze, K Node, S Takashima, H Asanuma, M Asakura, S Sanada, Y Shinozaki, H Mori, H Sato, T Kuzuya, M Hori
• Journal: Journal of molecular and cellular cardiology (J Mol Cell Cardiol) Vol. 33 Issue 9 Pg. 1727-37 (Sep 2001) ISSN: 0022-2828 [Print] England
• PMID: 11549351 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2001 Academic Press.

Chemical References

• Anti-Arrhythmia Agents
• Bicarbonates
• Enzyme Inhibitors
• Guanidines
• Sulfones
• Nitric Oxide
• cariporide
• Cyclic GMP
• Hydrochloric Acid
• NG-Nitroarginine Methyl Ester

Topics

• Acidosis (metabolism)
• Animals
• Anti-Arrhythmia Agents (pharmacology)
• Bicarbonates (pharmacology)
• Coronary Circulation (physiology)
• Coronary Vessels (drug effects, metabolism)
• Cyclic GMP (metabolism)
• Dogs
• Enzyme Inhibitors (pharmacology)
• Guanidines (pharmacology)
• Heart (drug effects, physiopathology)
• Hydrochloric Acid (pharmacology)
• Myocardial Ischemia (metabolism)
• Myocardium (metabolism)
• NG-Nitroarginine Methyl Ester (pharmacology)
• Nitric Oxide (biosynthesis)
• Sulfones (pharmacology)