Calcium overload--an important cellular mechanism in hypertension and arteriosclerosis.

Abstract

Arterial hypertension and arteriosclerosis are dramatic consequences of vascular calcium overload. Acute intracellular calcium overload of vascular smooth muscle cells produces hypercontractility. Hypertension develops if a general increase in systemic arteriolar tone leads to a rise in peripheral flow resistance. Moreover, progressive elevation of calcium destroys the structural integrity of the arterial and arteriolar walls. Thus, in various animals models, calcium overload initiates lesions of an arteriosclerotic character. Interestingly, conventional human coronary plaques also represent a calcium-dominated type of arteriosclerosis. With the advent of specific calcium antagonists, the pathogenic effects of calcium overload and its deleterious consequences have become, for the first time, accessible to therapeutic intervention. Accordingly, adequate treatment with calcium antagonists prevents calcium overload and can thereby protect arteries and arterioles from functional disturbances and structural damage. In spontaneously hypertensive rats, specific calcium antagonists of the verapamil, nifedipine and diltiazem type normalise blood pressure (BP) by reducing transmembrane calcium influx into vascular smooth muscle cells. However, in addition to controlling BP, these drugs also act as tissue protective agents. The long term effects of calcium antagonists such as verapamil in experimental hypertension include the prevention of severe arteriosclerosis, myocardial hypertrophy, and malignant nephrosclerosis. In humans, the antihypertensive efficacy of verapamil is well documented. Further clinical studies have yet to evaluate the antiarteriosclerotic and tissue protective potential of verapamil in humans.

• Authors: G Fleckenstein-Grün, M Frey, F Thimm, W Hofgärtner, A Fleckenstein
• Journal: Drugs (Drugs) Vol. 44 Suppl 1 Pg. 23-30 ( 1992) ISSN: 0012-6667 [Print] New Zealand
• PMID: 1283581 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Calcium Channel Blockers
• Calcium

Topics

• Animals
• Arteriosclerosis (drug therapy, metabolism)
• Calcium (antagonists & inhibitors, blood, pharmacology)
• Calcium Channel Blockers (therapeutic use)
• Humans
• Hypertension (drug therapy, metabolism)
• Mesenteric Arteries (pathology)
• Rats
• Rats, Inbred SHR