Roles of nitric oxide and adenosine in the regulation of coronary conductance in the basal state and during reactive hyperemia.
Nitric oxide (NO) and adenosine are important mediators in the regulation of coronary vascular tone and are released into the interstitium from the vascular endothelium and myocardium, respectively. The roles of these autacoids in the regulation of coronary flow in the basal and reactive hyperemic states were examined in Langendorff rabbit hearts perfused with oxygenated Krebs-Henseleit solution at 37 degrees C and 110 mmHg pressure. Instantaneous perfusion pressure-flow relationships were analyzed to derive coronary conductance both in the basal state and during the early phase of reperfusion (hyperemic state). N omega-nitro-L-arginine methyl ester (L-NAME) at increasing concentrations (10(-6) to 10(-4) mol/L) (n = 7) and 8-phenyltheophylline (8-PT) at increasing concentrations (10(-9) to 10(-6) mol/L) (n = 7) were applied to assess the role of NO and adenosine, respectively. L-NAME dose-dependently reduced the coronary conductance in both the basal and early hyperemic states, while 8-PT dose-dependently reduced conductance only in the hyperemic state. Changes in conductance during the early hyperemic phase correlated well with changes in the debt repayment ratio for either L-NAME (r = 0.94) or 8-PT (r = 0.99). These data suggest that a flow-related NO release mechanism regulates the coronary conductance in both the basal and hyperemic states while the metabolic regulation of adenosine release plays a role in the presence of ischemia.
Otomo
J
J
First Department of Internal Medicine, Yamagata University Medical School, Japan.
Nozaki
N
N
Tomoike
H
H
D000241:Adenosine / Q000502:physiology*; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006940:Hyperemia / Q000503:physiopathology*; D066298:In Vitro Techniques; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D058915:Purinergic P1 Receptor Antagonists; D011817:Rabbits; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology*
D004791:Enzyme Inhibitors; D058915:Purinergic P1 Receptor Antagonists; D009569:Nitric Oxide; D013806:Theophylline; C028322:8-phenyltheophylline; D000241:Adenosine; D019331:NG-Nitroarginine Methyl Ester