Prevention of salt-dependent cardiac remodeling and enhanced gene expression in stroke-prone hypertensive rats by the long-acting calcium channel blocker lacidipine

Objective To analyze the effect of the long-acting calcium channel blocker lacidipine on cardiovascular remodeling induced by salt loading in a genetic model of hypertension. Design We examined the influence of threshold doses of lacidipine, with little blood-pressure lowering effect, on cardiac weight and gene expression in stroke-prone spontaneously hypertensive rats (SHRSP). Methods SHRSPs (8-week-old) were randomly allocated to four groups: control, salt-loaded SHRSP and salt-loaded SHRSP treated with lacidipine at 0.3 and 1 mg/kg per day. Systolic blood pressure was measured by the tail-cuff method. At the end of 6 weeks of treatment, ventricles were collected and weighed. Ventricular messenger RNA was extracted and subjected to Northern blot analysis. Results Lacidipine (0.3 mg/kg per day) not only prevented the salt-dependent cardiac hypertrophy and the slight increase in systolic blood pressure induced by salt, but also prevented, largely or completely, salt-dependent increases in ventricular levels of several gene products: skeletal and cardiac alpha-actin, beta-myosin heavy chain (beta-MHC), type I collagen, long-lasting (L)-type calcium channel and preproendothelin-1. At a higher dose of 1 mg/kg per day, lacidipine further decreased systolic blood pressure below the level of control SHRSP, completely prevented salt-dependent overexpression of the beta-MHC gene and markedly attenuated salt-dependent overexpression of the transforming growth factor-beta, gene, Conclusions Lacidipine prevents the cardiac remodeling and enhanced gene expression induced by salt loading in SHRSP at doses that only minimally affect the high systolic blood pressure. (C) 1998 Lippincott Williams & Wilkins.