title: Rapid large artery remodeling following the administration and withdrawal of calcium channel blockers in spontaneously hypertensive rats.
abstract: Chronic treatment with several antihypertensive agents, including calcium channel blockers, may interfere with remodeling of large arteries and increased arterial stiffness. We hypothesize that even a short, seven-day administration of calcium channel blockers might alter an aortic remodeling in spontaneously hypertensive rat (SHR). Male SHR and normotensive WKY rats (n=14 each) were treated by either vehicle, vasculoselective calcium channel blocker nifedipine (1mg/kg/day) or cardiac/vascular calcium channel blockers diltiazem (5mg/kg/day) or verapamil (4 mg/kg/day, n=6 for each treatment) subcutaneously twice daily for seven days. Additional SHR rats were randomized for termination 24, 72 or 120 h (n=5 each) after the withdrawal of nifedipine. Systolic blood pressure was measured by tail cuff and thoracic aorta was collected for histomorphometric and functional analysis including acetylcholine-induced endothelium-dependent relaxation. Seven-day administration of diltiazem and nifedipine, but not verapamil decreased blood pressure in SHR. All drugs significantly attenuated abnormal aortic wall thickness, cross-sectional area and media-to-lumen ratio, but only nifedipine improved impaired endothelium-dependent relaxation. Following the withdrawal of nifedipine, all measured parameters returned back to control SHR values within 72 h. Seven-day treatment with distinct calcium channel blockers attenuates hypertensive remodeling of aorta, which might be, in case of nifedipine, reactivated even by a very short withdrawal of the drug. Therefore, vasculoprotection by calcium channel blockers is not restricted to a prolonged blood pressure modulation, but occurs rapidly. These findings could be relevant for an intervention in augmented vascular stiffness and related cardiovascular risk.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University, Bratislava, Slovakia.
authors.forename: Vaclav
authors.initials: V
authors.lastname: Vaja
authors.forename: Peter
authors.initials: P
authors.lastname: Ochodnicky
authors.forename: Peter
authors.initials: P
authors.lastname: Krenek
authors.forename: Jan
authors.initials: J
authors.lastname: Klimas
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Bajuszova
authors.forename: Jan
authors.initials: J
authors.lastname: Kyselovic
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology*; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use; D004110:Diltiazem / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D004727:Endothelium / Q000187:drug effects / Q000503:physiopathology; D006973:Hypertension / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009543:Nifedipine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D013997:Time Factors; D014700:Verapamil / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D002121:Calcium Channel Blockers; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine