MODULATION OF LEFT AND RIGHT-VENTRICULAR BETA-ADRENERGIC RECEPTORS FROM SPONTANEOUSLY HYPERTENSIVE RATS WITH LEFT-VENTRICULAR HYPERTROPHY AND FAILURE

Inotropic responsiveness to beta-adrenergic stimulation is generally f ound to be depressed in cardiac hypertrophy and failure. To investigat e whether inotropic responsiveness is associated with alterations in b eta-adrenergic receptors in spontaneously hypertensive rats (SHR), we studied left ventricular myocardial contractile responses to isoproter enol and beta-adrenergic receptor density and affinity in age-matched rats (18 to 24 months), including SHR without heart failure, SHR with evidence of heart failure, and normotensive control Wistar-Kyoto rats (WKY). In the baseline state, papillary muscles from failing SHR demon strated decreased isometric tension development and a reduction in max imal rate of tension development relative to normotensive WKY and comp ensated SHR. Compared with WKY, beta-adrenergic receptor density of th e left ventricle was unchanged in nonfailing SHR and increased in fail ing SHR (P<.05 versus WKY and nonfailing SHR), and beta-adrenergic rec eptor affinity did not differ among groups. In the right ventricle, be ta-adrenergic receptor density was decreased in failing SHR relative t o WKY and nonfailing SHR, and beta-adrenergic receptor affinity was no t different among groups. Muscle preparations did not exhibit a positi ve inotropic response to 10(-8) to 10(-5) mol/L isoproterenol or 6.3 m u mol/L forskolin in either failing or nonfailing SHR, whereas a posit ive inotropic response to both drugs was observed in the normotensive WKY. The lusitropic response to isoproterenol and forskolin was intact and similar in both SHR groups and WKY. The findings suggest that in the SHR model of heart failure, impaired intrinsic left ventricular my ocardial function and depressed inotropic responsiveness to beta-adren ergic stimulation are not associated with downregulation of the beta-a drenergic receptor. Impaired inotropic responses, with intact lusitrop ic responses, to both isoproterenol and forskolin are consistent with the concept that ''downstream'' events are responsible for impaired in otropy in response to beta-adrenergic stimulation in the SHR with chro nic left ventricular hypertrophy and failure.