Effects of the Heterodimeric Neurotoxic Phospholipase A[sub.2] from the Venom of IVipera nikolskii/I on the Contractility of Rat Papillary Muscles and Thoracic Aortas

Phospholipases A[sub.2] (PLA[sub.2] s) are a large family of snake toxins manifesting diverse biological effects, which are not always related to phospholipolytic activity. Snake venom PLA[sub.2] s (svPLA[sub.2] s) are extracellular proteins with a molecular mass of 13–14 kDa. They are present in venoms in the form of monomers, dimers, and larger oligomers. The cardiovascular system is one of the multiple svPLA[sub.2] targets in prey organisms. The results obtained previously on the cardiovascular effects of monomeric svPLA[sub.2] s were inconsistent, while the data on the dimeric svPLA[sub.2] crotoxin from the rattlesnake Crotalus durissus terrificus showed that it significantly reduced the contractile force of guinea pig hearts. Here, we studied the effects of the heterodimeric svPLA[sub.2] HDP-1 from the viper Vipera nikolskii on papillary muscle (PM) contractility and the tension of the aortic rings (ARs). HDP-1 is structurally different from crotoxin, and over a wide range of concentrations, it produced a long-term, stable, positive inotropic effect in PMs, which did not turn into contractures at the concentrations studied. This also distinguishes HDP-1 from the monomeric svPLA[sub.2] s, which at high concentrations inhibited cardiac function. HDP-1, when acting on ARs preconstricted with 10 μM phenylephrine, induced a vasorelaxant effect, similar to some other svPLA[sub.2] s. These are the first indications of the cardiac and vascular effects of true vipers’ heterodimeric svPLA[sub.2] s.