Effects of papaverine on isolated rabbit papillary muscle

The effect of papaverine on the positive inotropic response to isoprenaline and to calcium was studied on the rabbit isolated papillary muscle; theophylline and the calcium antagonistic D600 were used for comparison. The dose—response curve for isoprenaline was shifted to the left by papaverine (3 × 10 −6 to 3 × 10 −5 M), in a dose-dependent manner, while that for calcium was not affected by the same concentration. In this respect papaverine was about 30 times more potent than theophylline. In the presence of papaverine isoprenaline induced arrhythmic contractions of the papillary muscle: the incidence of arrhythmic contractions correlated to the concentration of papaverine. Papaverine 10 −5 to 10 −4 M caused only a positive inotropic response whereas 3 × −10 to 10 −3 M induced a biphasic response, i.e., after a positive inotropic effect followed a negative one. In the presence of 3 × 10 −4 M papaverine isoprenaline failed to cause a positive inotropic response but exclusively induced arrhythmic contractions. Calcium, on the other hand, readily antagonized the negative inotropic effectof papaverine (3 × 10 −4 M) and caused a contracture of the papillary muscle. The results indicate that papaverine (3 × 10 −6 to 10 −5 M) like theophylline (10 −4 to 10 −3 M) produces its effect by phosphodiesterase inhibition and thereby specifically potentiates the response through β-adrenoceptor stimulation. In higher concentrations (3 × 10 −4 to 10 −3 M) it act as a calcium antagonistic, like D600, and furthermore may interact with calcium moving through myocardial cell membranes to cause a contracture via a mechanism which it shares with theophylline.