Roles of calcium channels and alpha adrenergic receptors on cardiovascular and renal functions of acute hypercalcemic hypertensive dogs

Abstract

This investigation was performed to study the mechanism(s) responsible for alteration on blood pressure, cardiovascular and renal functions following the acute hypercalcemia by using calcium channel blocker (Verapamil) and selective alpha-1 adrenergic blocker (Prazosin). Twenty nine adult mongel dogs were devided into six groups. Group I, control group, recieved an intravenous infusion of isotonic saline solution. Group II, animals recieved an intravenous infusion of 400 mEq/L calcium chloride solution in the rate of 0.025 ml/kg/min Group III, animals recieved an intravenous infusion of 400 mEq/L calcium chloride solution which combined with pretreatment of an intravenous infusion of low dose (6 ug/kg/min) of calcium channel blocker (Verapamil). Group IV, animals treated in the same manner as in group III but pretreated with a high dose of Verapamil(12 ug/kg/min). Group V, animals treated in the same manner as in group III but pretreated with selective alpha-1 adrenergic blocker (Prazosin)in the dose of 20 ug/kg/min. Group VI, animals treated in the same manner as in group III but pretreated with the combination both of high dose of verapamil and Prazosin. General circulation and renal hemodynamics were measured before the Caci2, infusion and observed for 3 hours after the Caci2, infusion. Acute hypercalcemia of animals in group II without pretreated with Verapamil or Prazosin produced the sharp increases in mean arterial blood pressure and total peripheral vascular resistance. An effective renal plasma flow, renal blood flow and glomerular filtration rate decreased significantly throughout the experimental period. Animals in group III, IV or v pretreated with Verapamil or Prazosin alone could not maintain the hypotensive effect during acute hypercalcemia. But in the same time interval, animals in group VI pretreated with the combination both of high dose of verapamil and Prazosin could maintain the hypotensive effect. Total peripheral vascular resistance did not alter significantly. The increases of effective renal plasma flow, renal blood flow and glomerular filtration rate were observed while renal vascular resistance declined significantly till the end of the experiment. It was indicated that during hypercalcemia, plasma concentration of inorganic phosphorus increased significantly whereas plasma concentration of sodium, potassium and chloride showed no significant change. All hypercalcemic animals showed decreases in heart rate, cardiac output, plasma volume and blood volume while there were increased in renal fraction, filtration fraction, the rate of urine flow, fractional excretion of sodium, potassium, chloride and inorganic phosphorus. The hypercalcemic animals showed an increase in either Osmolar clearance or free water clearance. These results suggest that acute hypercalcemia induced hypertension could mediate by direct effect of calcium through the calcium channels and indirect effect by increasing the activity of alpha-1 adrenergic receptors. Kidney plays a major role in the control of blood pressure. Hypercalcemia produced the decreases in renal hemodynamics and renal functions as well as the defective in normal concentrating ability of the kidney.