Effect of Russell's viper venom on renal functions during intrarenal infusion of thromiboxane synthetase inhibitor in dogs

Abstract

This investigation was performed to study the effect of Russell’s viper venom on renal function during intrarenal arterial infusion of tromboxane synthetase in dog. Twenty adult male mongrel dogs were divided into four groups. Group I, control group received an intravenous injection of 0.05 mg/kg of Russell’s viper vemom. Group II, after 0.05 mg/kg of the venom was injected 40 min, continuous infusion of imidazole (thromboxane systhetase inhibitor) 2 mg/kg/min was administered via left renal artery throu[gh]out the experiment. Group III, animals rec[e]ived 2 mg/kg/min of imidazole by intrarenal arterial infusion. After 20 min of the infusion they were envenomated as same as group I while the infusion of imidazole was sustained throughout the experim[e]nt . Group IV the animals rec[e]ived 0.5 mg/kg/min of imidazole, and treated in the same manner of group III. Envenomation produced profound hypotension promptly in both group I and II for 30 min then gradually increased to approach pre-envenomation level. Group III, imidazole alone increased mean arterial blood pressure and antagonized hyp[er]tensive effect of envenomation which was not apparent in group IV. After envenomation 50 min, mean arterial pressure in all imidazole-treated groups rose above pre-envenomation level markedly. Venom injection induced a prompt increase in packed cell volume in all groups. This elevation was persistently significant throughout the experiment in imdazole-treated groups while an increase in group I was transient. Effective renal blood flow and glomerular filtration rate decreased in all groups associated with a fall in blood pressure. In imidazole-treated group exhibited the deterioration of renal blood flow and glomerular filtration rate through[h]out the experiment inspite of recovery of blood pressure. These declines were significantly different from control group (group I), especially the prominent was seen in the left kidney. Renal vascular resistant was markedly increased in left kidney of group III and IV. Urine flow rate decreased by envenomation in all groups. After 30 min of venom injection it gradually increased in group I and became above the control level. In contrast with imidazole-treated group, urine flow rate remained at the low level throughout the experiment. This difference compared to control group was significant in group II and III. The response of osmolar clearance to Russell’s viper venom was similar urine flow rate. While plasma osmolarity in imidazole-treated group was elevated which was significantly different from group I in 70 min per[io]d of envenomation. Plasma electrolyte concentration for sodium, poteassium, chloride, calcium and inorganic phosphorus showed no significant change. In imidazole-treated groups all electrolytes excretion of the left kidney were significantly decreased in comparison to group I. Fractional excretion of all electrolytes were strikingly elevated in left kidney of group III. In addition, fractional excretion of inorganic phosphorus also increased in left kidney of group I and II at 30 min period which imidazole infusion did not start. These results suggest that intrarenal arterial continuous infusion of imidazole aggravated renal function of envenomated dogs which correlated to an increase in renal vascular resistance. Imidazole may enhance effect of Russell’s viper venom by interfering tubular cell function. Effects of imidazole other than thromboxane systhetase inhibitor, such as cyclooxygenase inhibitor and sympathomimetic activity may mask the ben[e]ficial effect of thromboxane synthesis blocker.