Effects of monoamine oxidase inhibitors on isoproterenol-induced cardiomegaly in rats

Abstract

Cardiac enlargement was induced in rats by isoproterenol (5 mg/kg, sc) administered twice daily for 4 days. The magnitude of the cardiomegaly was significantly less in animals which had been pretreated 3 days before and then during the isoproterenol treatments with one of the following monoamine oxidase inhibitors: β-phenylethylhydrazine (phenelzine), 3-methyl-3-piperidinopyrazine (modaline), N-benzyl- N-methyl-2-propynylamine (pargyline), 2-phenylcyclopropylamine (tranylcypromine), 1 benzyl-2-(5-methyl)-3-isoxazolylcarbonylhydrazine (isocarboxazid). These compounds inhibited heart monoamine oxidase activity 71–96% when administered for 3 days in doses smaller than those required to significantly antagonize isoproterenol-induced cardiomegaly. N-Isonicotinyl- N-β-( N-benzylcarboxamido)ethylhydrazine (nialamide) inhibited monoamine oxidase activity but did not protect the animals from the cardiac enlargement elicited by isoproternol. Nicotinic acid hydrazide (isoniazid) was inactive in both regards. The levels of protein, RNA and DNA, as well as the incorporation of glycine-2- 14C into the protein or nucleic acids, were significantly elevated in the hearts of rats treated with 2 doses of isoproterenol (5 mg/kg, sc). When rats were pretreated with phenelzine (20 mg/kg, sc) or pargyline (40 mg/kg, sc), the following cardiac biochemical parameters were significantly reduced when compared with those from animals treated with isoproterenol alone: (1) wet weight, (2) protein, (3) RNA, (4) glycine-2- 14C incorporation into protein, RNA, and DNA.