role of magnesium and calcium ions in atrial natriuretic peptide secretion

For the purpose of examining the role of calcium and magnesium ions in the secretory process of atrial natriuretic peptide [ANP], we studied the effects of hypercalcemia, digitalis "Lanoxine", calcium ion channel blocker "verapamil", hypermagnesemia, potassium ion channel blocker "Glibenclamid", and potassium ion channel opener "cromakalim" on plasma concentration of immunoreactive ANP [ir ANP]. Pentobarbital-anesthetized dogs [n-36] were divided into-6-equal groups [6 each] and treated separately with calcium chloride infusion [0.136 mmol/Kg/min-10 min]. Lanoxine injection [30 micro g/Kg], verapamil injection [300 micro g/Kg], magnesium sulfate infusion [0.168 mmol/Kg/min-10 min] after an initial bolus dose of 1.5 mmol/Kg, glibenclamid injection [0.3 mg/Kg], and cromakalim injection [10 micro g/Kg]. Plasma ir ANP concentrations, mean arterial pressure [MAP], heart rate [HR] and serum calcium and magnesium concentrations were measured. With calcium chloride and magnesium sulfate infusions, serum calcium and magnesium levels and plasma ir ANP concentrations were significantly increased. Also, lanoxine and K[+] -channel blocker "glibenclamid" caused a significant increase in plasma ir ANP concentration while verapamil and the K[+]-channel opener "cromakalim" resulted in a significant decrease. Neither calcium chloride nor lanoxine produced a significant effect on heart rate, but both significantly increased MAP. In contrast, magnesium sulfate and verapamil produced a significant decrease in MAP and HR while glibenclamid and cromakalim were associated with insignificant changes in both HR and MAP. These results suggest that calcium ions may play a key role in the secretory process of ANP and indicate that magnesium ions may also influence ANP secretion by acting via modulation of K[+] -channels

Measurement of plasma verapamil levels by high-performance liquid chromatography

1. We have developed an alternative procedure for the measurement of verapamil levels in human plasma by reverse-phase high performance liquid chromatography with fluorimetric detection. 2. Prior to assay, plasma is submitted to a double extraction procedure, using first n-heptane in alkaline medium and then an acid phosphate buffer. Flecainide, a compound not related to verapamil, is used as internal standard. Mean recoveries of 70 and 63 per cent were obtained for verapamil and flecainide, respectively. 3. The sensitivity (5 ng/ml), reproducibility (inter-assay per cent CV = 1.7-8.7; intra-assay per cent CV = 2-4) and high recovery during sample clean-up make this method useful for the quantitation of verapamil in therapeutic monitoring and pharmacokinetic studies. 4. The method is illustrated with the pharmacokinetic results obtained for 14 healthy male volunteers who received a single 240 mg dose of the commercially available tablets of Dilacoron Retard 240 mg. The mean values for the area under the curve from 0 to 24 h (AUC[0-24]), maximum achieved concentration (Cmax) and time to achieve the maximum concentration (Tmax) were 863 ng h-1 ml-1, 112 ng/ml and 4 h, respectively