Depressed inotropic response to beta-adrenoceptor agonists in the presence of advanced cardiac hypertrophy in hearts from rats with induced aortic stenosis and from spontaneously hypertensive rats.

OBJECTIVE: To study the inotropic response to beta-adrenoceptor stimulation in isolated hypertrophied hearts from hypertensive rats. DESIGN AND METHODS: Cardiac hypertrophy was induced in Wistar rats by stenosing the abdominal aorta. Functional responses to isoprenaline, dobutamine, terbutaline and salbutamol were measured in paced (5 Hz), aortically stenosed hearts (18-20 and 32-34 weeks of age) and compared with those of sham-operated spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. RESULTS: Following aortic stenosis, which was accompanied by less hypertension than that sustained by SHR, the Wistar rat hearts showed more pronounced cardiac hypertrophy. An initially equal inotropic response to the beta-adrenoceptor agonists (18-20 weeks) was reduced to 45% at 32-34 weeks in SHR but not in WKY rat hearts. The response to beta-adrenoceptor stimulation in the hypertrophied Wistar rat hearts was reduced at 18-20 weeks to 30% and at 32-34 weeks to 10% of controls, respectively. The response by all hypertrophied hearts to forskolin and N,2'-O-dibutyryladenosine 3':5' monophosphate was also diminished. CONCLUSIONS: The impaired contractile response to beta-adrenoceptor agonism is more clearly related to cardiac hypertrophy than to hypertension.