Relation between Blood Pressure and Plasma Catecholamine Concentration after Administration of Calcium Antagonists to Rats

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Three types of calcium antagonists, diltiazem, verapamil and nicardipine, were separately infused into Sprague-Dawley (SD) rats (under pentobarbital anesthesia n=5) through the left femoral vein at four different flow rates. Mean arterial blood pressure, heart rate and the concentration of plasma catecholamines (CAs), epinephrine (E), norepinephrine (NE) and dopamine (DA), were measured for each calcium antagonist, and the correlations between them were studied. Blood samples were collected within the infusion from common juglar vein. Plasma concentrations of CAs were determined by a HPLC-ethylenediamine condensation reaction-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=-α log X+m (Y, blood pressure; X, concentration of plasma NE; α, slope; and m, intercept). The correlation coefficients (rs) were -0.950 (diltiazem), -0.975 (verapamil) and -0.978 (nicardipine) (versus -0.734 for control). The α 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 maintaining blood pressure reduced by nicardipine is less than that observed following the infusion of diltiazem and verapamil. Similar good inverse correlations between blood pressure and the logarithm of plasma concentration of E were observed with the three drugs infused (γ=-0.928,-0.966 and -0.948 for diltiazem, verapmil and nicardipine, respectively). A slight correlation (γ=-0.810) was obtained between blood pressure and the logarithm of plasma DA concentration following the infusion of nicardipine. On the infusion of nicardipine, the heart rate remained at the same value as the starting point during the first and second dose infusion (0.50 and 1.01 μg/kg/min, respectively) and was then reduced significantly after the additional infusions (2.02μg/kg/min), whereas the heart rates started to decrease from the first point of treatment with diltiazem and verapamil.
社団法人日本薬学会の論文
1994-07-15

Relation between Blood Pressure and Plasma Catecholamine Concentration after Administration of Calcium Antagonists to Rats

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