Beta1-adrenergic receptor activation decreases ANP release via cAMP-Ca2+ signaling in perfused beating rabbit atria.
OBJECTIVE
Although a beta-adrenoceptor (beta-AR) blockade-induced increase in plasma atrial natriuretic peptide (ANP) levels is implicated in the therapeutic significance of beta-AR antagonists, the role of beta-AR in the regulation of ANP release is not clearly defined. The purpose of the present study was to define the role of beta-AR subtypes and the mechanisms responsible for regulation of atrial ANP release.


METHODS
Experiments were performed in isolated perfused beating rabbit atria, including measurement of atrial contractile response, cAMP efflux, and atrial myocyte ANP release.


RESULTS
beta-AR activation with (-)-isoproterenol decreased ANP release concomitantly with increases in cAMP efflux concentration, atrial dynamics, stroke volume and pulse pressure in a concentration-dependent manner. The ANP response was inversely related to the change in cAMP efflux concentrations. The isoproterenol-induced decrease in ANP release was inhibited by beta(1)-AR blockade with CGP 20712A but not by beta(2)-AR blockade with ICI 118551. The isoproterenol-induced decrease in ANP release was attenuated by the L-type Ca(2+) channel antagonist nifedipine and the cAMP-dependent protein kinase inhibitor KT5720.


CONCLUSIONS
These findings suggest that beta(1)-AR activation decreases ANP release via cAMP- and Ca(2+)-dependent mechanisms.
Quan
He Xiu
HX
Department of Physiology, Jeonbug National University Medical School, Jeonju, Republic of Korea.
Jin
Jing Yu
JY
Wen
Jin Fu
JF
Cho
Kyung Woo
KW
D058665:Adrenergic beta-1 Receptor Agonists; D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism*; D006325:Heart Atria / Q000378:metabolism*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D011817:Rabbits; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism*; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism
D058665:Adrenergic beta-1 Receptor Agonists; D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists; D020746:Calcium Channels, L-Type; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D009320:Atrial Natriuretic Factor; D000242:Cyclic AMP; D007545:Isoproterenol; D002118:Calcium