Rapid large artery remodeling following the administration and withdrawal of calcium channel blockers in spontaneously hypertensive rats

Eur J Pharmacol. 2009 Oct 1;619(1-3):85-91. doi: 10.1016/j.ejphar.2009.08.003. Epub 2009 Aug 14.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta / drug effects*
  • Aorta / pathology
  • Aorta / physiopathology*
  • Blood Pressure / drug effects
  • Calcium Channel Blockers / administration & dosage*
  • Calcium Channel Blockers / pharmacology*
  • Calcium Channel Blockers / therapeutic use
  • Diltiazem / administration & dosage
  • Diltiazem / pharmacology
  • Diltiazem / therapeutic use
  • Endothelium / drug effects
  • Endothelium / physiopathology
  • Hypertension / drug therapy*
  • Hypertension / pathology
  • Hypertension / physiopathology*
  • Male
  • Muscle Contraction / drug effects
  • Nifedipine / administration & dosage
  • Nifedipine / pharmacology
  • Nifedipine / therapeutic use
  • Rats
  • Time Factors
  • Verapamil / administration & dosage
  • Verapamil / pharmacology
  • Verapamil / therapeutic use

Substances

  • Calcium Channel Blockers
  • Verapamil
  • Diltiazem
  • Nifedipine