Distinct roles for L- and T-type Ca2+ channels in regulation of atrial ANPrelease

Atrial secretion of atrial natriuretic peptide (ANP) has been shown to be r egulated by atrial workload. Although modulating factors for the secretion of ANP have been reported, the role for intracellular Ca2+ on the secretion of ANP has been controversial. The purpose of the present study was to def ine roles for L- and T-type Ca2+ channels in the regulation of ANP secretio n in perfused beating rabbit atria. BAY K 8644 (BAY K) increased atrial str oke volume and pulse pressure. BAY K suppressed ANP secretion and ANP conce ntration in terms of extracellular fluid (ECF) translocation concomitantly with an increase in atrial dynamics. BAY K shifted the relationship between ANP secretion and ECF translocation downward and rightward. These results indicate that BAY K inhibits myocytic release of ANP. In the continuous pre sence of BAY K, diltiazem reversed the effects of BAY K. Diltiazem alone in creased ANP secretion and ANP concentration along with a decrease in atrial dynamics. Diltiazem shifted relationships between ANP secretion and atrial stroke volume or ECF translocation leftward. The T-type Ca2+ channel inhib itor mibefradil decreased atrial dynamics. Mibefradil inhibited ANP secreti on and ANP concentration in contrast with the L- type Ca2+ channel inhibito r. These results suggest that activation of L- and T-type Ca2+ channels eli cits opposite effects on atrial myocytic release of ANP.