Hemodynamic and cardiac anti-hypertrophic actions of clonidine in Goldblatt one-kidney, one-clip rats.
In congestive heart failure, the chronic sympathetic hyperactivity contributes to a poor prognosis. In this respect, clonidine, a centrally acting sympathoinhibitory drug, has previously been tested in clinical trials. The aim of the current study was to evaluate the effects of clonidine on morbidity and mortality in an experimental model of cardiac hypertrophy associated with hypertension, renal failure, and intense sympathetic activation. One-kidney, one-clip Goldblatt hypertensive rats were treated orally with clonidine (200 microg/kg/d) during 30 days and were compared with untreated rats and with sham-operated animals. Cardiac hemodynamics, left ventricular volume and elasticity, cardiac morphometry and histology, and renal function were evaluated. A survival study was also performed. Clonidine normalized cardiac function, ventricular stiffness, and prevented ventricular structural remodeling. Moreover, despite a marked renal function impairment, survival of the animals was increased in the clonidine group. The centrally acting sympathoinhibitory drug clonidine exhibited marked cardioprotective properties. This study emphasized the interest of evaluating drugs whose aim is to treat congestive heart failure, in an experimental model of cardiac and renal failure.
Thomas
Lionel
L
Laboratoire de Neurobiologie et Pharmacologie Cardiovasculaire, Faculté de Médecine, Strasbourg, France.
Gasser
Bernard
B
Bousquet
Pascal
P
Monassier
Laurent
L
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D006332:Cardiomegaly / Q000188:drug therapy / Q000401:mortality / Q000503:physiopathology; D003000:Clonidine / Q000494:pharmacology / Q000627:therapeutic use*; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D006978:Hypertension, Renovascular / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015996:Survival Rate
D000959:Antihypertensive Agents; D003000:Clonidine