Calcium (Ca2+) is an inhibitory second messenger in the renin secretory process, and evidence suggests that first messengers can alter Ca2+ in the renin-secreting juxtaglomerular cells by altering Ca2+ influx, efflux, and mobilization pathways. Influx of Ca2+ through voltage-operated channels is one such pathway, and it has been suggested that pressure-induced changes in renin secretion (the baroreceptor mechanism) are mediated by depolarization-induced Ca2+ influx. On this basis, renin secretion should be stimulated by organic calcium channel antagonists; however, stimulation is only occasionally observed. Therefore, other effects of these substances counteract the stimulatory effects on renin secretion.