Species‐related differences in inotropic effects of angiotensin II in mammalian ventricular muscle: receptors, subtypes and phosphoinositide hydrolysis
Аннотация:Experiments were carried out to clarify the mechanisms responsible for variations in the positive inotropic effect (PIE) of angiotensin II (AII) on ventricular muscles from various mammals. We examined the density of All receptors, the relative proportions of receptor subtypes and the acceleration of the hydrolysis of phosphoinositide that was induced by AII, as well as the PIE of AII in ventricular muscles from the rabbit, dog, rat and ferret. In the rabbit, AII (1 μ m ) in the presence of bupranolol (0.3 μ m ) and prazosin (0.1 μ m ) elicited a concentration‐dependent PIE, which was antagonized by a selective AT 1 subtype antagonist, losartan, but not by an AT 2 antagonist, PD123319. AII did not have any inotropic effects in ventricular muscles from the dog, rat and ferret. Specific high‐affinity binding of [ 125 I]‐AII, with a similar K d value in each case (1–2 n m ), was observed with membrane fractions derived from ventricular muscle of all four species tested. In the rabbit, losartan and PD123319 each displaced approximately 50% of [ 125 I]‐AII specific binding having high affinity for the receptors, and indicating that AT 1 and AT 2 subtypes were present in equal numbers. In the other species the AT 1 subtype of receptors was predominant. In all four species AII caused a concentration‐dependent acceleration of the hydrolysis of phosphoinositide in ventricular slices that had been prelabelled with myo ‐[ 3 H]‐inositol. The results indicate that the signal‐transduction process distal to acceleration of the hydrolysis of phosphoinositide may be responsible for the wide range of species variations in the inotropic action of AII on mammalian ventricular myocardium.
