Verapamil impairs secretion of stimulated atrial natriuretic factor in humans

The adaptation of the secretory rate of atrial natriuretic factor to repeated adequate stimuli and the influence of the calcium antagonist verapamil on the release of atrial natriuretic factor were investigated in 16 patients. In eight patients (Group 1) right atrial pressure was abruptly increased by rapid right ventricular pacing for 4 min (stimulation I). After a 15 min interval, the identical stimulation was repeated (stimulation II). Eight patients (Group 2) underwent the same protocol but received 5 mg of verapamil intravenously after stimulation I. Pacing increased right atrial pressure in both groups identically by 70%. In Group 1, release of atrial natriuretic factor caused by the second stimulation (median 290 pg/ml over basal) was significantly (2.5-fold) larger than atrial natriuretic factor release induced by the first stimulation (median 116 pg/ml over basal). In the verapamil-treated patients (Group 2), the effect of right atrial pressure increase on release of atrial natriuretic factor was abolished after stimulation II. In both groups, changes in plasma concentrations of cyclic guanosine monophosphate corresponded to changes in atrial natriuretic factor concentrations. Thus, the myoendocrine cells are apparently capable of a fast upward regulation of their response to repeated secretory stimuli. Verapamil appears to block the stimulatory effect of a sudden increase in right atrial pressure upon release of atrial natriuretic factor.