Increase of atrial ANP release by 2,3-butanedione monoxime in beating rabbit atria.
2,3-Butanedione monoxime (BDM) is a chemical phosphatase and has been known to dissociate mechanical contraction in the excitation-contraction coupling via inhibition of myofibrillar ATPase. BDM has also been found to decrease sarcolemmal L-type Ca(2+) channel activity and intracellular Ca(2+) in cardiac myocytes. It has been shown that Ca(2+) entry via L-type Ca(2+) channels decreased atrial myocyte atrial natriuretic peptide (ANP) release. The purpose of the present study was to address the effects of BDM in the regulation of ANP release. Experiments were performed in perfused beating rabbit atria. BDM accentuated atrial myocyte ANP release concomitantly with a decrease in atrial stroke volume and pulse pressure in a concentration-dependent manner. The BDM-induced activation of ANP release was attenuated by the treatment with nifedipine, an inhibitor of L-type Ca(2+) channels. BDM further decreased atrial stroke volume and pulse pressure in the presence of nifedipine. Blockade of function of the sarcoplasmic reticulum with thapsigargin plus ryanodine slightly but not significantly attenuated the BDM-induced activation of ANP release. These data show that BDM is a potent stimulator for the ANP release and also suggest that the mechanism by which BDM activates atrial myocyte ANP release is related to inhibition of the L-type Ca(2+) channel activity. The present finding also suggests that the effects of ANP released may be considered in an occasion of uncoupling by BDM of the excitation-contraction coupling of cardiomyocytes.
Jin
Jing Yu
JY
Department of Physiology, Institute of Life Sciences, Taishan Medical University, Taian, Shandong, China.
Li
Dan
D
Wen
Jin Fu
JF
Cho
Kyung Woo
KW
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000378:metabolism; D003931:Diacetyl / Q000031:analogs & derivatives* / Q000494:pharmacology; D006325:Heart Atria / Q000187:drug effects* / Q000378:metabolism; D011817:Rabbits; D011863:Radioimmunoassay
D020746:Calcium Channels, L-Type; C004717:diacetylmonoxime; D009320:Atrial Natriuretic Factor; D003931:Diacetyl