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 blo cker lacidipine on cardiovascular remodeling induced by salt loading i n a genetic model of hypertension. Design We examined the influence of threshold doses of lacidipine, with little blood-pressure lowering ef fect, on cardiac weight and gene expression in stroke-prone spontaneou sly hypertensive rats (SHRSP). Methods SHRSPs (8-week-old) were random ly allocated to four groups: control, salt-loaded SHRSP and salt-loade d SHRSP treated with lacidipine at 0.3 and 1 mg/kg per day. Systolic b lood pressure was measured by the tail-cuff method. At the end of 6 we eks of treatment, ventricles were collected and weighed. Ventricular m essenger RNA was extracted and subjected to Northern blot analysis. Re sults Lacidipine (0.3 mg/kg per day) not only prevented the salt-depen dent cardiac hypertrophy and the slight increase in systolic blood pre ssure induced by salt, but also prevented, largely or completely, salt -dependent increases in ventricular levels of several gene products: s keletal and cardiac alpha-actin, beta-myosin heavy chain (beta-MHC), t ype I collagen, long-lasting (L)-type calcium channel and preproendoth elin-1. At a higher dose of 1 mg/kg per day, lacidipine further decrea sed systolic blood pressure below the level of control SHRSP, complete ly prevented salt-dependent overexpression of the beta-MHC gene and ma rkedly attenuated salt-dependent overexpression of the transforming gr owth factor-beta, gene, Conclusions Lacidipine prevents the cardiac re modeling 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.