RELATION BETWEEN BLOOD-PRESSURE AND PLASMA-CATECHOLAMINE CONCENTRATION AFTER ADMINISTRATION OF CALCIUM-ANTAGONISTS TO RATS

Three types of calcium antagonists, diltiazem, verapamil and nicardipi ne, were separately infused into Sprague-Dawley (SD) rats (under pento barbital anesthesia n = 5) through the left femoral vein at four diffe rent flow rates. Mean arterial blood pressure. heart rate and the conc entration of plasma catecholamines (CAs), epinephrine (E), norepinephr ine (NE) and dopamine (DA), were measured for each calcium antagonist, and the correlations between them were studied. Blood samples were co llected within the infusion from common juglar vein. Plasma concentrat ions of CAs were determined by a HPLC-ethylenediamine condensation rea ction-peroxyoxalate chemiluminescence detection system (HPLC-ED-PO-CL) . The plasma concentration of CAs increased corresponding to the blood pressure reduction. The reduction induced by each calcium antagonist correlated with the logarithm of plasma NE concentration. The relation was expressed as Y=-alpha log X + m (Y, blood pressure; X, concentrat ion of plasma NE; alpha, slope; and m, intercept). The correlation coe fficients (rs) were -0.950 (diltiazem), -0.975 (verapamil) and -0.978 (nicardipine) (versus -0.734 for control). The alpha for nicardipine ( 108.4) was greater than those of diltiazem (85.4) and verapamil (80.8) (versus 31.0 for control), meaning that blood pressure reduction was greater in the case of nicardipine than diltiazem and verapamil, with an identical increment of plasma NE concentration. These data indicate that the contribution of the sympathetic nervous system to maintainin g blood pressure reduced by nicardipine is less than that observed fol lowing the infusion of diltiazem and verapamil. Similar good inverse c orrelations between blood pressure and the logarithm of plasma concent ration of E were observed with the three drugs infused (r=-0.928, -0.9 66 and -0.948 for diltiazem, verapmil and nicardipine, respectively.). A slight correlation (r=-0.810) was obtained between blood pressure a nd the logarithm of plasma DA concentration following the infusion of nicardipine. On the infusion of nicardipine, the heart rate remained a t the same value as the starting point during the first and second dos e infusion (0.50 and 1.01 mug/kg/min, respectively) and was then reduc ed significantly after the additional infusions (2.02 mug/kg/min), whe reas the heart rates started to decrease from the first point of treat ment with diltiazem and verapamil.