Effect of chronic administration of clonidine and propranolol on the myocardium of spontaneously hypertensive rats.
Chronic administration of clonidine to six month old spontaneously hypertensive rats (SHR) by continuous infusion with Alzet minipumps resulted in a decreased systolic arterial pressure, a decrease in heart weight, protein content and the incorporation of precursors of cellular protein and glycoprotein into the myocardium. Chronic administration of propranolol to SHR for three consecutive weeks by Alzet minipump reduced systolic arterial pressure but did not reverse the indices of myocardial hypertrophy. Chronic administration of propranolol to SHR for three consecutive weeks resulted in myocardial necrosis in each of the SHR tested. Because both clonidine and propranolol inhibit sympathetic activity to the myocardium, whereas propranolol also blocks myocardial beta receptors, the data support the conclusion that the ability of clonidine to reverse myocardial hypertrophy in the SHR cannot result from withdrawal of sympathetic tone to the myocardium. Moreover, since both drugs caused an equivalent reduction in pressure, the effects of clonidine cannot result from a decrease in afterload to the myocardium. The data support the conclusion that clonidine may reverse myocardial hypertrophy by a direct action on the myocardium or by inhibiting the synthesis or release of circulating or trophic factors which may mediate myocardial hypertrophy. Moreover, if propranolol-induced focal myocardial necrosis is found to occur in other species, caution should be utilized in the use of propranolol for the treatment of essential hypertension in man.
D000818:Animals; D001834:Body Water / Q000378:metabolism; D006332:Cardiomegaly / Q000139:chemically induced; D003000:Clonidine / Q000494:pharmacology*; D006025:Glycosaminoglycans / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D006973:Hypertension / Q000503:physiopathology*; D009124:Muscle Proteins / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009336:Necrosis / Q000139:chemically induced; D009929:Organ Size / Q000187:drug effects; D011433:Propranolol / Q000494:pharmacology*; D051381:Rats
D006025:Glycosaminoglycans; D009124:Muscle Proteins; D011433:Propranolol; D003000:Clonidine