CARDIAC-HYPERTROPHY INDUCED BY ALPHA-ADRENERGIC AND BETA-ADRENERGIC RECEPTOR STIMULATION

The aim of the study was to examine whether stimulation of alpha- and beta-adrenergic receptors in intact rats induces cardiac hypertrophy a nd to characterize the metabolic alterations that precede or accompany the process of hypertrophy. Cardiac beta-adrenergic receptors were st imulated with a single subcutaneous injection of 25 mg/kg isoprotereno l. This led to an increase in the cardiac cAMP level which was followe d by the sequential enhancement of adenine nucleotide biosynthesis and protein synthesis. The increase in adenine nucleotide and protein syn thesis induced by isoproterenol was prevented by propranolol (50 mg/kg ) within the first 5 hours. Norepinephrine, given as a continuous intr avenous infusion of 0,2 mg/kg for 3 days, induced an increase in heart rate, mean aortic pressure and total peripheral resistance. Cardiac o utput was slightly reduced. The cardiac RNA/DNA ratio and the left ven tricular weight/body weight ratio were significantly increased by abou t 40%. Simultaneous intravenous administration of the a-receptor block er prazosin (0.1 mg/kg/h) and of the beta-receptor blocker metoprolol (1 mg/kg/h) reversed the functional changes and attenuated the increas e in the RNA/DNA ratio induced by norepinephrine. The left ventricular weight/body weight ratio was within the range of the control values. Selective stimulation of alpha-adrenergic receptors by continuous intr avenous infusion of norfenephrine (2 mg/kg/h) for 3 days increased hea rt rate and total peripheral resistance, while cardiac output was sign ificantly lower. The RNA/DNA and left ventricular weight/body weight r atios were increased Prazosin attenuated the increase in the RNA/DNA r atio induced by norfenephrine and prevented the development of cardiac hypertrophy. In the isolated perfused working rat heart, norpinephrin e (3 x 10(-8)M) increased the expression of the protooncogenes c-fos a nd c-myc after 30 and 60 minutes, respectively. This increase occurred at about the same time as that induced by volume overload (increase o f preload from 8 to 16 cm H2O) and pressure overload (increase of afte rload from 80 to 100 cm H2O) but was more pronounced. In intact rats, norepinephrine elicited an increase in the mRNA and activity of glucos e-6-phosphate dehydrogenase, the first and regulating enzyme of the ox idative pentose phosphate pathway, in a time-dependent manner It is su ggested that this may be part of a long-term homeostatic mechanism to keep the cardiac adenine nucleotide level in the normal range.