title: L/N-type calcium channel blocker suppresses reflex aldosterone production induced by antihypertensive action.
abstract: The L/N-type calcium channel blocker cilnidipine has been shown to suppress aldosterone production induced by angiotensin II (Ang II) in vitro. In addition, cilnidipine also suppresses the reflex tachycardia induced by its antihypertensive action in vivo. We investigated the effects of cilnidipine on the reflex aldosterone production induced by its antihypertensive action, to identify the differences in the effects of cilnidipine from those of the L-type calcium channel blocker nifedipine. Male SHR/Izm rats were anesthetized by intraperitoneal injection of pentobarbital sodium, and administered an intravenous infusion of saline supplemented or not with Ang II for 30 min. Blood pressure was monitored continuously in the femoral artery. Each of the calcium channel blockers under study was administered intravenously as a bolus through the femoral vein 1 min after the start of the Ang II infusion, and blood samples were collected 30 min after the start of the Ang II infusion. Following administration at nonhypotensive doses, all calcium channel blockers tended to decrease the plasma aldosterone. In particular, cilnidipine significantly suppressed the plasma aldosterone levels. On the other hand, under the condition of Ang II-induced hypertension, administration of a hypotensive dosage of cilnidipine showed no effect on the plasma aldosterone levels, whereas a hypotensive dosage of nifedipine significantly increased the plasma aldosterone levels. Our results suggest that the L/N-type calcium channel blocker cilnidipine reduces the plasma aldosterone level by suppressing the aldosterone production induced by reflex upregulation of the renin-angiotensin-aldosterone system associated with reduction of the blood pressure.
authors: Exploratory Research Laboratories, Research Center, Ajinomoto Pharmaceuticals Co., Ltd., 1-1 Suzuki-cho, Kawasaki-ku, Kawasaki, Kanagawa, Japan. shizuka_aritomi@ajinomoto.com
authors: Shizuka
authors: S
authors: Aritomi
authors: Tomoyuki
authors: T
authors: Konda
authors: Michihiro
authors: M
authors: Yoshimura
mesh_terms: D000450:Aldosterone / Q000097:blood*; D000804:Angiotensin II / Q000008:administration & dosage; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects* / Q000378:metabolism; D020864:Calcium Channels, N-Type / Q000187:drug effects* / Q000378:metabolism; D004095:Dihydropyridines / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D015536:Down-Regulation; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D007275:Injections, Intravenous; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D012018:Reflex / Q000187:drug effects*; D012084:Renin-Angiotensin System / Q000187:drug effects
chemical_list: D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D004095:Dihydropyridines; D000804:Angiotensin II; D000450:Aldosterone; C065927:cilnidipine; D009543:Nifedipine