Effects of methysergide or phenoxybenzamine on the renal and cardiovascular responses to endotoxin in rats.

Renal and cardiovascular responses to an intravenous infusion of endotoxin (2.5 mg/kg/hr for four hours) were studied in unanesthetized rats. Cardiac output was reduced while total body and renal vascular resistance increased. Mean systemic blood pressure was only slightly reduced. The renal excretion of sodium, potassium, and water were reduced with no significant effect on urine concentration. Glomerular filtration rate, renal plasma flow, and filtration fraction were also reduced. alpha-Adrenergic blockade with phenoxybenzamine did not prevent any of the above changes, but a 5-HT blocking agent, methysergide, greatly reduced the effect of endotoxin on total peripheral resistance and blocked the effect of endotoxin on renal vascular resistance and renal blood flow. In rats treated with phenoxybenzamine or methysergide, endotoxin caused a large fall in the filtration fraction and extreme reduction in the rate of sodium excretion. These changes possibly resulted from decreases in the glomerular ultrafiltration coefficient or in capillary hydrostatic pressure.