Regulation of therapeutic apoptosis: a potential target in controlling hypertensive organ damage.

Abstract

Cell growth and survival are potential therapeutic targets for the control of complications associated with hypertension. In most cardiovascular disorders, cardiac fibroblasts and large-vessel smooth muscle cells can replicate and thus contribute to the disease. We propose that cardiovascular hyperplasia may be reversed via therapeutic apoptosis induction with drugs that are safe and already used in the clinic. We first reported that, irrespective of the drug class, those drugs that are able to induce regression of cardiovascular hypertrophy are also able to reverse cardiovascular hyperplasia via apoptosis. Drugs active in this regard include inhibitors of the renin-angiotensin system, calcium channel blockers, and beta-blockers. Moreover, the effects of these drugs on cell survival is not merely secondary to blood pressure reduction. Therapeutic apoptosis in the cardiovascular system of the spontaneously hypertensive rat is characterized by a rapid and transient onset following initiation of antihypertensive treatment. Herein, the induction and termination of therapeutic apoptosis during drug treatment of hypertension will be briefly reviewed and supported by novel data suggesting that reversal of cardiovascular hyperplasia is associated with reduced cell growth and a resistance to further induction of therapeutic apoptosis, as shown in spontaneously hypertensive rats receiving an intermittent regime of nifedipine therapy. We propose that the presence of a cell subpopulation with defective cell cycle regulation may determine organ susceptibility to undergo therapeutic apoptosis.

• Authors: Denis Deblois, Bun-Seng Tea, Diane Beaudry, Pavel Hamet
• Journal: Canadian journal of physiology and pharmacology (Can J Physiol Pharmacol) Vol. 83 Issue 1 Pg. 29-41 (Jan 2005) ISSN: 0008-4212 [Print] Canada
• PMID: 15759048 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Antihypertensive Agents

Topics

• Animals
• Antihypertensive Agents (therapeutic use)
• Apoptosis (drug effects)
• Cardiovascular System (drug effects, pathology)
• Humans
• Hypertension (complications, drug therapy, pathology)
• Hypertrophy (etiology, pathology, prevention & control)