Hypertension and pathologic cardiovascular remodeling: a potential therapeutic role for T-type calcium antagonists.
Increased myocardial mass (cardiac hypertrophy, left ventricular hypertrophy [LVH]) is an example of the widespread structural cardiovascular changes, often referred to as remodeling, that may be present in association with sustained high blood pressure. LVH strongly predicts myocardial infarction, stroke, and cardiovascular death in patients with hypertension. As a result, prevention or reversal of hypertensive LVH is widely accepted as a desirable therapeutic goal. Although the molecular mechanisms responsible for remodeling are unclear, it is believed that mechanical, endocrine, paracrine, and autocrine factors control the remodeling process. Certain antihypertensive drugs may have particularly favorable long-term effects in that they prevent and correct these structural changes in addition to reducing arterial pressure. However, the mechanism by which they achieve these effects is not well understood. It is theorized that angiotensin-converting enzyme inhibitors do so by preventing the generation of growth-promoting/mitogenic peptides and that beta-blockers interfere with the growth-promoting effects of catecholamines. In experimental models, the selective blockade of T-type calcium-ion (Ca2+) channels with mibefradil has been demonstrated to have antiproliferative effects in both the renal and cardiac vasculature; in patients with LVH, mibefradil reduced the left ventricular mass index. Therefore, blockade of T-type Ca2+ channels may be useful in the prevention or regression of cardiovascular remodeling. However, further research will be required before the clinical implications of these findings can be assessed.
Giles
T D
TD
School of Medicine in New Orleans, Louisiana State University Medical Center, New Orleans, USA.
D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D006332:Cardiomegaly / Q000503:physiopathology*; D003327:Coronary Disease / Q000503:physiopathology*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology
D002121:Calcium Channel Blockers