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.


METHODS
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-beta1 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.
Kyselovic
J
J
Laboratoire de Pharmacologie, Université Catholique de Louvain, Brussels, Belgium.
Morel
N
N
Wibo
M
M
Godfraind
T
T
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D006332:Cardiomegaly / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D002561:Cerebrovascular Disorders / Q000150:complications / Q000188:drug therapy / Q000235:genetics; D004095:Dihydropyridines / Q000627:therapeutic use*; D005500:Follow-Up Studies; D015870:Gene Expression / Q000187:drug effects; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D018995:Myosin Heavy Chains / Q000187:drug effects / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D011897:Random Allocation; D051381:Rats; D011918:Rats, Inbred SHR; D012965:Sodium Chloride / Q000633:toxicity; D020257:Ventricular Remodeling / Q000187:drug effects* / Q000235:genetics
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D012333:RNA, Messenger; C060285:lacidipine; D012965:Sodium Chloride; D018995:Myosin Heavy Chains