Effects of Echis carinatus Venom on the Haemodynamy and Contractility of Vascular and Visceral Smooth Muscle of Rats.

Abstract Echis carinatus is considered to be one of the most dangerous snakes in the world because of its venom toxicity and high population densities in rural agriculture areas. However, little information is available on the pharmacological effects of venom from this snake on haemodynamy and vasculature smooth muscle contractility. The haemodynamic alterations induced by the intravenous administration of Echis carinatus venom was investigated in anaesthetized rats. Injection of several doses of venom (1, 3, 5, and 7 mu g kg (- 1)) decreased the arterial blood pressure. For instance, injection of 3 mu g kg(-1) of Echis carinatus venom reduced the mean arterial blood pressure from 107 +/- 4 to 71 +/- 4 mmHg (p < 0.05). Exposure of the rat isolated vas deferens preparations to Echis carinatus venom (1 mu g ml(-1)) significantly reduced the contractile responses to epinephrine (10 mu g ml(- 1)) without changing the response to KCl (50 mM). To investigate the effects of venom on peripheral vascular resistance, mesenteric bed was removed and perfused with Krebs solution. Addition of different concentrations of venom (1, 3, and 10 mu g ml(-1)) to the precontracted mesenteric bed (with phenylephrine, 5 x 10(- 4) M) decreased the contraction in a concentration-dependent manner. However, preincubation of mesenteric bed with atropine (0.1 mu M), L-NAME (10 (-5) M) or indomethacin (10(-5) M) prevented this effect of the venom. These results may suggest that the inhibitory effect of the venom on nonvascular smooth muscle (such as vas deferens) contractions is a postsynaptic phenomenon. Furthermore, it could be suggested that the cardiovascular effects of Echis carinatus venom are mediated through multiple mechanisms such as activation of muscarinic receptors as well as production of nitric oxide and prostaglandins.