[Role of adrenergic receptor system in canine left ventricular hypertrophy]

Although sympathetic nervous system and catecholamines have been postulated to play an important role in the development of myocardial hypertrophy, the precise mechanism is still ill-defined. We then developed two experimental canine models; 12 dogs with surgical cardiac denervation by the method of Geis et al, inducing up-regulation of myocardial adrenergic receptors, and 12 dogs with chronic infusion of subhypertensive dose of norepinephrine (NE) at a rate of 0.04 mg/kg/day. After two months, both models induced myocardial hypertrophy, as indicated by significant increases in left ventricular (LV) wall thickness and cell diameter as compared with 14 sham-operated control dogs. Cardiac denervation remarkably depleted myocardial NE contents, while plasma NE remained unchanged. Both alpha-1 and beta receptors were unregulated, Bmax increasing by 90% and 50% respectively. Decrease in myocardial cyclic-AMP content was relatively small as compared with the marked reduction in myocardial NE, probably by the compensatory augmentation of beta receptor system activity. Chronic NE infusion also reduced myocardial NE content possibly due to stimulation of presynaptic alpha-2 receptor inhibiting NE synthesis and release. Number of alpha-1 and beta receptors also increased by 90% and 30% respectively, while myocardial cyclic-AMP content remained unchanged. These observations indicate that neither direct stimulation of NE on the myocardial cell nor increased in cyclic-AMP is the mechanism for cardiac hypertrophy in both models.(ABSTRACT TRUNCATED AT 250 WORDS)