Ursolic acid increases the secretion of atrial natriuretic peptide in isolated perfused beating rabbit atria.
Ursolic acid is reported to have beneficial effects on the regulation of cardiovascular homeostasis. However, the effects of ursolic acid on cardiac hormone secretion are yet to be defined. The present study was designed to test the effects of ursolic acid on the secretory and contractile functions of the atria. Experiments were conducted in isolated perfused beating rabbit atria. We measured the changes in atrial dynamics, pulse pressure, stroke volume, cAMP efflux, as well as the secretion of atrial natriuretic peptide (ANP). Ursolic acid increased ANP secretion and mechanical dynamics in a concentration-dependent manner. The inhibition of L-type Ca(2+) channels with nifedipine attenuated the ursolic acid-induced increase in ANP secretion but not mechanical dynamics. The inhibition of K(+)(ATP) channels with glibenclamide attenuated the ursolic acid-induced increase in ANP secretion-but not atrial dynamics-in a concentration-dependent manner. The selective Na(+)-K(+)-ATPase inhibitor ouabain blocked the ursolic acid-induced increase in atrial dynamics but not ANP secretion. These findings show that ursolic acid increases ANP secretion via its activation of K(+)(ATP) channels and subsequent inhibition of Ca(2+) entry through L-type Ca(2+) channels in rabbit atria. These data also suggest that ursolic acid increases atrial dynamics via its inhibition of Na(+)-K(+)-ATPase activity.
Professional Graduate School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk, Republic of Korea.
Hao Zhen
HZ
Cui
Jin Fu
JF
Wen
Hye Ran
HR
Choi
Xiang
X
Li
Kyung Woo
KW
Cho
Dae Gill
DG
Kang
Ho Sub
HS
Lee
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005905:Glyburide / Q000494:pharmacology; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism; D054086:KATP Channels / Q000187:drug effects / Q000378:metabolism; D011817:Rabbits; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014315:Triterpenes / Q000008:administration & dosage / Q000494:pharmacology*; D000097245:Ursolic Acid
D009320:Atrial Natriuretic Factor; D002118:Calcium; D020746:Calcium Channels, L-Type; D005905:Glyburide; D054086:KATP Channels; D000254:Sodium-Potassium-Exchanging ATPase; D014315:Triterpenes; D000097245:Ursolic Acid