[Effect of long-term administration of vasodilators and "antitrophic" agents on the structure and function of the heart in hypertensive rats].
In this study, we determined whether the persistency of cardiac hypertrophy after chronic vasodilation therapy with minoxidil (minox) was associated with functional or metabolic alterations in hypertensive rat hearts before, during and after an ischemic insult. In addition, we investigated the effects of the simultaneous administration of difluoromethylornithine (dfmo), a substance that could block hypertrophy by a direct inhibition of protein synthesis. Four groups of male Wistar rats were prepared: 1) normotensive controls (n = 8), 2) untreated renovascular hypertensive rats (HT, n = 15), 3) hypertensives treated with minox (8 mg/kg, n = 19), 4) hypertensives treated with minox and dfmo (1.7 g/kg, n = 20). After 21 days of treatment, the animals were sacrificed. In a small number of hearts, ornithine decarboxylase (ODC) activity was assayed in order to verify that dfmo, which is a suicide inhibitor of ODC, had effectively interrupted the polyamines pathway. The other hearts were prepared for retrograde perfusion at 35 degrees C and at constant flow (10 ml/min x g). Cardiac function was monitored via the balloon inserted in the left ventricle (LV) and the following protocol was applied: a) baseline period (24 min), b) ischemia (24 min), c) recovery (36 min). Finally, the hearts were weighed and LV wall thickness and inner radius were measured. Blood pressure was maintained near normotension in the two treated groups. Mean systolic pressure (in mmHg) was 145 +/- 4 with minox and 144 +/- 3 with minox + dfmo versus 181 +/- 4 in the HT group (p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)
Carlier
P
P
Laboratoire d'hypertension, CHU de Liège, Belgique.
Smelten
N
N
Gilles
R
R
Rorive
G
G
D000818:Animals; D006332:Cardiomegaly / Q000188:drug therapy* / Q000503:physiopathology; D004359:Drug Therapy, Combination; D000518:Eflornithine / Q000494:pharmacology* / Q000627:therapeutic use; D006352:Heart Ventricles / Q000187:drug effects* / Q000473:pathology; D006439:Hemodynamics / Q000187:drug effects*; D006978:Hypertension, Renovascular / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008914:Minoxidil / Q000494:pharmacology* / Q000627:therapeutic use; D008955:Models, Cardiovascular; D009955:Ornithine Decarboxylase / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D008914:Minoxidil; D009955:Ornithine Decarboxylase; D000518:Eflornithine
Effets de l'administration chronique d'un vasodilatateur et d'un agent "antitrophique" sur la structure et la fonction du coeur de rat hypertendu.