TY - JOUR T1 - Adenosine receptor-mediated alterations in prostacyclin production and cardiac function in the isolated rabbit heart. JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 660 LP - 668 VL - 261 IS - 2 AU - C Cano AU - K U Malik Y1 - 1992/05/01 UR - http://jpet.aspetjournals.org/content/261/2/660.abstract N2 - The subtype of adenosine receptor linked to cardiac prostacyclin (PGI2) synthesis, measured as immunoreactive 6-keto-PGF1 alpha, was investigated in the rabbit heart perfused with Krebs' buffer at 20 ml/min. Adenosine (6.4-50 nmol) decreased 6-keto-PGF1 alpha synthesis, coronary perfusion pressure (PP) and myocardial contractility (dp/dt max), whereas higher doses (200 nmol) increased 6-keto-PGF1 alpha output and decreased PP, heart rate (HR) and dp/dt max. Injections (3.2-50 nmol) or infusion (0.6 microM) of A1 receptor agonist 1-deaza,2-chloro,N6 cyclopentyladenosine increased 6-keto-PGF1 alpha production and decreased HR and PP without affecting dp/dt max. 1-Deaza,2-chloro,N6 cyclopentyladenosine 100 to 200 nmol produced similar effects as lower doses except that it decreased transiently PP and reduced dp/dt max. 1,3-Dipropyl,8-cyclopentylxanthine (0.06 microM) prevented the effects of 1-deaza,2-chloro,N6 cyclopentyladenosine (50 mumol) and adenosine (10 microM) to increase 6-keto-PGF1 alpha output and decrease HR and minimized the decrease in dp/dt max. A2 receptor agonist 2-[p-(2-carboxyethyl)-phenethylamino]-5'-N-ethylcarboxamido-ade nos ine (1.6-12.5 nmol) or 0.6 microM decreased 6-keto-PGF1 alpha output, PP and dp/dt max without changes in HR. 3,7-Dimethyl-1-propargylxanthine prevented 2-[p-(2-carboxyethyl)-phenethylamino]-5'-N-ethylcarboxamido adenosine-induced decrease in 6-keto-PGF1 alpha output, PP and dp/dt max; HR was not altered by this agent. These data suggest that stimulation of A2 receptors reduce cardiac PGI2 synthesis and PP, but activation of A1 adenosine receptors increased PGI2 synthesis, produced vasoconstriction and decreased HR.(ABSTRACT TRUNCATED AT 250 WORDS) ER -