title: Blocking T-type Ca2+ channels with efonidipine decreased plasma aldosterone concentration in healthy volunteers.
abstract: Efonidipine can block both L- and T- type Ca2+ channels. In a previous in vitro study, we clarified that efonidipine dramatically suppresses aldosterone secretion from human adrenocortical tumor cells during angiotensin II (Ang II)- and K+-stimulation, whereas nifedipine, a dominant L-type Ca2+ channel antagonist, does not. This study was conducted to assess the in vivo effects of efonidipine and nilvadipine on the plasma aldosterone concentration. Placebo, 40 mg of efonidipine, or 2 mg of nilvadipine was administered to five healthy male volunteers. Hemodynamic parameters (pulse rate [PR] and blood pressure [BP]), plasma concentrations of neurohormonal factors (plasma renin activity, Ang II, aldosterone, and adrenocorticotropic hormone [ACTH]), and serum concentrations of Na+ and K+ were measured before and 6 h after administration of the agents. All three agents had little effect on PR and BP. Efonidipine and nilvadipine significantly increased plasma renin activity and Ang II. Both had little effect on ACTH, Na+, and K+. The plasma aldosterone concentration was significantly decreased after efonidipine treatment (88.3 +/- 21.3 to 81.6 +/- 24.9 pg/ml, p = 0.0407), whereas it was significantly increased after nilvadipine treatment (66.5 +/- 12.2 to 82.17 +/- 16.6 pg/ml, p = 0.0049). Placebo had little effect on neurohormonal factors. Efonidipine decreased plasma aldosterone concentration despite the increase in plasma renin activity and Ang II, suggesting that T-type Ca2+ channels may also play an essential role in the secretion of aldosterone in healthy human volunteers.
authors.affiliation: First Department of Internal Medicine, Nara Medical University, Kashihara, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Okayama
authors.forename: Keiichi
authors.initials: K
authors.lastname: Imagawa
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Naya
authors.forename: Hajime
authors.initials: H
authors.lastname: Iwama
authors.forename: Satoshi
authors.initials: S
authors.lastname: Somekawa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kawata
authors.forename: Manabu
authors.initials: M
authors.lastname: Horii
authors.forename: Tamio
authors.initials: T
authors.lastname: Nakajima
authors.forename: Shiro
authors.initials: S
authors.lastname: Uemura
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Saito
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000450:Aldosterone / Q000097:blood*; D000804:Angiotensin II / Q000097:blood; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020747:Calcium Channels, T-Type / Q000187:drug effects*; D018592:Cross-Over Studies; D003864:Depression, Chemical; D004095:Dihydropyridines / Q000494:pharmacology*; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D008297:Male; D018377:Neurotransmitter Agents / Q000097:blood; D009543:Nifedipine / Q000031:analogs & derivatives / Q000494:pharmacology; D009596:Nitrophenols / Q000494:pharmacology*; D009943:Organophosphorus Compounds / Q000494:pharmacology; D012083:Renin / Q000097:blood; D014882:Water-Electrolyte Balance / Q000187:drug effects
chemical_list: D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D004095:Dihydropyridines; D018377:Neurotransmitter Agents; D009596:Nitrophenols; D009943:Organophosphorus Compounds; C035100:nilvadipine; D000804:Angiotensin II; C066425:efonidipine; D000450:Aldosterone; D000324:Adrenocorticotropic Hormone; D012083:Renin; D009543:Nifedipine