α<inf>1</inf>-adrenoceptor subtypes and inositol phosphates production in heart ventricles of spontaneously hypertensive rats

Dolores Ivorra, Silvia Gascon, Elisabet Vila, Albert Badia

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    Abstract

    To study potential cardiac α1-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 Kdvalues 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 α1B-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 α1A- and α1B-adrenoceptor subtypes in SHR and WKY rats. In addition, [3H]inositol phosphate accumulation in response to cardiac α1-adrenoceptor stimulation by NE was significantly reduced in SHR as compared with WKY rats although the EC50values 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 α1-adrenoceptors with consequently reduced inositol phosphate turnover. These results are compatible with the reported decrease in the positive inotropic effect mediated through myocardial α1-adrenoceptors in spontaneous hypertension. © 1993 Raven Press. Ltd.
    Original languageEnglish
    Pages (from-to)931-936
    JournalJournal of Cardiovascular Pharmacology
    Volume21
    Issue number6
    DOIs
    Publication statusPublished - 1 Jan 1993

    Keywords

    • Cardiac α -adrenoceptors 1
    • Inositol phosphate turnover
    • Spontaneously hypertensive rats
    • [ H]Prazosin binding 3

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