Impaired inotropic response to α1 but not to β-adrenoceptor stimulation in isolated hearts from spontaneously hypertensive rats


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Abstract

Objectives:Hypertension in humans and experimental animals is known to be associated with an increase in left ventricular myocardial mass. The development of cardiac hypertrophy is not caused by increased blood pressure alone; the autonomic nervous system may also play an important role.Design:The functional responses to the β-adrenoceptor agonists isoprenaline, dobutamine, salbutamol and terbutaline, and the α1-adrenoceptor agonists methoxamine, cirazoline and phenylephrine were studied in isolated (Langendorff) hearts from spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto (WKY) controls. The results were compared with data from radioligand binding experiments.Results:There was no significant difference in the increase of left ventricular pressure induced by all β-adrenoceptor agonists studied in SHR and WKY rat hearts. Although there was no significant difference in the response to phenylephrine, the inotropic responses to cirazoline and methoxamine proved to be significantly weaker in hearts from SHR than in those from WKY rats. Binding experiments with 3H-prazosin revealed no differences in density or affinity for cardiac tissues from SHR and WKY rats.Conclusions:Long-standing hypertension leads to an impaired response of the isolated heart to α1-padrenoceptor stimulation, without changes in α1-receptor density or affinity. It seems likely that changes in postreceptor events are responsible for the impaired inotropic response to α1-adrenoceptor agonists in hearts from SHR.

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