A method to evaluate the response of the coronary circulation of perfused rat heart to adenosine.
Exogenous adenosine causes a monophasic dilation of the coronary vessels in paced, perfused rat heart preparations. Because levels of endogenous adenosine in paced hearts may mask the presence of high potency adenosine receptors, we have developed a method to measure coronary vascular responses in a potassium-arrested heart. Hearts from adult male, Wistar rats were perfused at a constant flow rate of 10 mL/min in the nonrecirculating, Langendorff mode, using Krebs-Henseleit buffer. After 30 min, coronary perfusion pressure was 44 +/- 1 mmHg (mean +/- SEM). Hearts were then perfused with a modified Krebs-Henseleit buffer containing 35 mM potassium. Coronary perfusion pressure increased by 84 +/- 3 mmHg. Adenosine-induced reductions in coronary perfusion pressure were expressed as a percentage of the maximal increase in pressure produced by modified Krebs-Henseleit buffer from the equilibration level. A concentration-response curve for adenosine (n = 6) was biphasic and best described by the presence of two adenosine receptors, with negative log EC50 values of 8.8 +/- 0.3 and 4.3 +/- 0.1, representing 29 +/- 3 and 71 +/- 3%, respectively, of the observed response. Interstitial adenosine sampled by microdialysis during potassium arrest was 25% of the concentration found in paced hearts. Endogenous adenosine in nonarrested hearts may obscure the biphasic response of the coronary vessels to adenosine.
Harrison
G J
GJ
Rotary Centre for Cardiovascular Research, School of Science, Griffith University, Nathan, Australia.
Harden
F A
FA
Jordan
L R
LR
Varela
J I
JI
Willis
R J
RJ
D000241:Adenosine / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000502:physiology*; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D018047:Receptors, Purinergic P1 / Q000187:drug effects*; D012977:Sodium Nitrite / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
D018047:Receptors, Purinergic P1; D014665:Vasodilator Agents; D006632:Histamine; D000241:Adenosine; D012977:Sodium Nitrite