Experimental vasoprotection by calcium antagonists against calcium-mediated arteriosclerotic alterations

J Cardiovasc Pharmacol. 1994;24 Suppl 2:S75-84.

Abstract

According to chemical analyses, the development of conventional human coronary artery plaques from "fatty streaks" to "fibrous plaques" and "complicated lesions" is dominated by progressive mural calcium (Ca) incorporation. The atherogenic significance of Ca ions and arterial Ca overload was examined under the influence of nicotine, oxidatively modified low-density lipoproteins, spontaneous hypertension, and an elevated extracellular Ca concentration or vitamin D3. Experiments were carried out either in vitro on cultured medial cells of rats or in vivo on various types of experimental arteriosclerosis of rats. Suitable Ca antagonists (verapamil, diltiazem, nifedipine, or nitrendipine) prevented experimental Ca overload of arterial walls and transmembrane Ca uptake into cultured medial cells produced by risk factors. Thus they protected, in vivo and/or in vitro, against the atherogenic potential of Ca ions, i.e., migration, proliferation, matrix production and intracellular Ca overload of vascular smooth-muscle cells, as well as calcification of elastic fibers. The data indicate that various Ca-consuming processes demand a progressive uptake of Ca into arterial walls if Ca-dominated types of arteriosclerosis develop. Under experimental conditions, specific Ca antagonists inhibit Ca-mediated arteriosclerotic alterations by preventing progressive mural Ca incorporation.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Arteriosclerosis / drug therapy*
  • Arteriosclerosis / etiology
  • Arteriosclerosis / prevention & control
  • Calcium / metabolism*
  • Calcium Channel Blockers / pharmacology
  • Calcium Channel Blockers / therapeutic use*
  • Cells, Cultured
  • Cholecalciferol / toxicity
  • Cholesterol / metabolism
  • Coronary Vessels / drug effects*
  • Coronary Vessels / pathology
  • Diltiazem / pharmacology
  • Diltiazem / therapeutic use
  • Disease Models, Animal
  • Humans
  • Hypertension / complications
  • Hypertension / drug therapy
  • Middle Aged
  • Muscle, Smooth, Vascular / drug effects*
  • Muscle, Smooth, Vascular / pathology
  • Nicotine / toxicity
  • Nifedipine / pharmacology
  • Nifedipine / therapeutic use
  • Nitrendipine / pharmacology
  • Nitrendipine / therapeutic use
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Rats, Sprague-Dawley
  • Risk Factors
  • Verapamil / pharmacology
  • Verapamil / therapeutic use

Substances

  • Calcium Channel Blockers
  • Cholecalciferol
  • Nicotine
  • Cholesterol
  • Nitrendipine
  • Verapamil
  • Diltiazem
  • Nifedipine
  • Calcium