Modulation of left and right ventricular beta-adrenergic receptors from spontaneously hypertensive rats with left ventricular hypertrophy and failure.

Abstract

Inotropic responsiveness to beta-adrenergic stimulation is generally found to be depressed in cardiac hypertrophy and failure. To investigate whether inotropic responsiveness is associated with alterations in beta-adrenergic receptors in spontaneously hypertensive rats (SHR), we studied left ventricular myocardial contractile responses to isoproterenol 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 demonstrated decreased isometric tension development and a reduction in maximal rate of tension development relative to normotensive WKY and compensated SHR. Compared with WKY, beta-adrenergic receptor density of the left ventricle was unchanged in nonfailing SHR and increased in failing SHR (P < .05 versus WKY and nonfailing SHR), and beta-adrenergic receptor affinity did not differ among groups. In the right ventricle, beta-adrenergic receptor density was decreased in failing SHR relative to WKY and nonfailing SHR, and beta-adrenergic receptor affinity was not different among groups. Muscle preparations did not exhibit a positive inotropic response to 10(-8) to 10(-5) mol/L isoproterenol or 6.3 mumol/L forskolin in either failing or nonfailing SHR, whereas a positive 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 myocardial function and depressed inotropic responsiveness to beta-adrenergic stimulation are not associated with downregulation of the beta-adrenergic receptor.(ABSTRACT TRUNCATED AT 250 WORDS)