α1-Adrenoceptor Subtypes and Inositol Phosphates Production in Heart Ventricles of Spontaneously Hypertensive Rats

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Abstract
To study potential cardiac alpha 1-adrenoceptor changes in the stage of established hypertension, [3H]prazosin binding characteristics and norepinephrine (NE) stimulated production of inositol phosphates in the ventricular tissue of spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto control rats (WKY) were determined. The maximum number of cardiac [3H]prazosin binding sites was significantly reduced in SHR as compared with WKY rats, but the Kd values were similar in both groups of animals. Distribution of the [3H]prazosin-labeled high- and low-affinity binding sites for WB 4101 was similar in SHR and WKY rats. Pretreatment of ventricular heart membranes with the irreversible alpha 1B-adrenoceptor-selective antagonist chloroethylclonidine resulted in the same percentage of loss of specific [3H]prazosin binding in both groups of rats. Together, these results showed a similar ratio of alpha and alpha 1B-adrenoceptor subtypes in SHR and WKY rats. In addition, [3H]inositol phosphate accumulation in response to cardiac alpha 1-adrenoceptor stimulation by NE was significantly reduced in SHR as compared with WKY rats although the EC50 values were not significantly different in the two strains of animals. Thus, we conclude that in an established stage of hypertension there is a specific loss in the number of cardiac alpha 1-adrenoceptors with consequently reduced inositol phosphate turnover. These results are compatible with the reported decrease in the positive inotropic effect mediated through myocardial alpha 1-adrenoceptors in spontaneous hypertension.

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