STUDIES ON ISOPROTERENOL-INDUCED CARDIOMEGALY IN RATS

1. 1. Isoproterenol (ISO) (5 mg. per kilogram, subcutaneously) induced maximal increases in the wet and dry weights of the four chambers of the rat heart when administered twice daily for 10 days. The degree of cardiomegaly was related to the duration of ISO treatment but was not greater, in most instances, after 20 to 80 mg. per kilogram than after 5 mg. per kilogram. The size of the heart regressed when ISO treatment was discontinued. Propranolol antagonized the ISO response. 2. 2. The cardiomegaly induced by ISO was accompanied by microscopic evidence of infarctlike cardiac necrosis. The severity of damage, although not quantitated, appeared to increase with the dosage of ISO or the duration of treatment. 3. 3. Total and extracellular cardiac water, Na+, Ca++, and Cl- increased in relation to ISO dose. Heart K+ increased after 1 or 5 mg. per kilogram but decreased after 80 mg. per kilogram of ISO administered twice daily for 2 days. Mg++ decreased to the same extent with all doses. 4. 4. The levels of cardiac protein, RNA, and DNA were augmented by ISO treatment with RNA increasing more than DNA. The incorporation of C14-labelled amino acids into the protein of the heart, but not of the skeletal muscle, was enhanced by ISO. 5. 5. Catecholamine contents (microgram per gram) but not levels (microgram per heart) decreased as the size of the heart increased with ISO treatment. 6. 6. ISO (5 mg. per kilogram) elicited prolonged tachycardia and hypotension in unanesthetized rats prepared with chronic, aortic catheters. © 1969.