title: Comparison of the cardioprotective and renoprotective effects of the L/N-type calcium channel blocker, cilnidipine, in adriamycin-treated spontaneously-hypertensive rats.
abstract: Cilnidipine is an L/N-type calcium channel blocker (CCB). The effects of cilnidipine on N-type channels give it unique organ-protective properties via the suppression of hyperactivity in the sympathetic nervous system (SNS) and renin-angiotensin-aldosterone system (RAAS). In the present study, we compared the effects of cilnidipine and amlodipine (an L-type CCB) on cardiac and renal functions in spontaneously-hypertensive rats injected with adriamycin (ADR). After the weekly administration of ADR for 3 weeks, spontaneously-hypertensive rats were orally administered cilnidipine (20 mg/kg per day), amlodipine (3 mg/kg per day), or vehicle once daily for 4 weeks. A control group received saline rather than ADR, followed by vehicle for 4 weeks. Cilnidipine and amlodipine produced similar reductions in blood pressure after 4 weeks. Cilnidipine ameliorated ADR-induced heart and kidney damage, whereas amlodipine slightly improved cardiac echocardiographic parameters, but did not protect against ADR-induced renal damage. Cilnidipine (but not amlodipine) suppressed the reflex SNS and RAAS hyperactivity caused by their antihypertensive effects. Furthermore, cilnidipine and amlodipine treatment decreased the urinary levels of adrenocortical hormones. The protective effects of cilnidipine against ADR-induced renal and cardiac dysfunction might be associated with its blockade of N-type calcium channels, in addition to its pleiotropic actions, which include the inhibition of the RAAS.
authors.affiliation: Research Institute, Ajinomoto Pharmaceuticals, Kanagawa, Japan; Department of Pharmacology and Therapeutics, Toho University, Chiba, Japan.
authors.forename: Shizuka
authors.initials: S
authors.lastname: Aritomi
authors.forename: Eri
authors.initials: E
authors.lastname: Harada
authors.forename: Kazumi
authors.initials: K
authors.lastname: Sugino
authors.forename: Mai
authors.initials: M
authors.lastname: Nishimura
authors.forename: Tarou
authors.initials: T
authors.lastname: Nakamura
authors.forename: Akira
authors.initials: A
authors.lastname: Takahara
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects* / Q000378:metabolism; D020864:Calcium Channels, N-Type / Q000187:drug effects* / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects*; D004095:Dihydropyridines / Q000494:pharmacology*; D004195:Disease Models, Animal; D004317:Doxorubicin; D005355:Fibrosis; D006331:Heart Diseases / Q000097:blood / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D006973:Hypertension / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007674:Kidney Diseases / Q000097:blood / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D011918:Rats, Inbred SHR; D012084:Renin-Angiotensin System / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology
chemical_list: D000959:Antihypertensive Agents; D015415:Biomarkers; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D004095:Dihydropyridines; D004317:Doxorubicin; C065927:cilnidipine
keywords: adriamycin; calcium channel blockers; cilnidipine