The effect of phosphodiesterase inhibitors on guinea-pig cardiac responses to histamine and isoprenaline

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Abstract
(1) The effect of phosphodiesterase inhibitors was studied on right atrial rate, left atrial tension and left ventricular papillary muscle tension responses to histamine and isoprenaline. (2) Only responses mediated via β-adrenoceptors and H2-receptors were potentiated by theophylline. This is proposed to be due to its phosphodiesterase inhibiting properties and therefore indicates the involvement of cAMP in these responses. (3) 3-Isobutyl-1-methylxanthine was approximately 30 times more potent than theophylline in producing leftward shifts of isoprenaline left atrial tension curves. The potentiating effect of papaverine was masked by an opposing depressant action. (4) Left ventricular papillary muscle tension responses to histamine were enhanced by the phosphodiesterase inhibitors confirming the reported involvement of cAMP in the right ventricle. (5) The left atrial tension dose-response curves to histamine were not potentiated. Single doses revealed a biphasic response consisting of an H1-receptor mediated component and one resistant to both H1- and H2-receptor antagonists. Neither component was potentiated suggesting no involvement of cAMP.