Properties of cardiac alpha- and beta-adrenoceptors in spontaneously hypertensive rats

Abstract

The effects of isoprenaline, Ca2+ and phenylephrine (in the presence of propranolol) on force of contraction were studied in isolated electrically driven papillary muscles of spontaneously hypertensive rats (SHR) and age-matched (14-18 weeks) Wistar Kyoto control rats (WK). Cardiac alpha- and beta-adrenoceptors were characterized by radioligand binding studies. The positive inotropic effect of isoprenaline in SHR was less effective than in control rats. The EC50 values did not differ in both groups. In SHR, isoprenaline was less effective than Ca2+ to increase force of contraction whereas in WK it had the same effectiveness as Ca2+. The positive inotropic effect of phenylephrine in the presence of propranolol was similar in SHR and WK. In SHR, both the densities of cardiac alpha- and beta-adrenoceptors were reduced. In beta-adrenoceptor binding experiments, the nonhydrolysable GTP analog Gpp(NH)p caused a rightward shift of agonist competition curves of isoprenaline. Biphasic competition curves revealed a similar percentage of low and high affinity sites in SHR and WK, respectively. In alpha-adrenoceptor binding experiments, Gpp(NH)p caused no detectable shift of agonist competition curves with norepinephrine. It is suggested that cardiac beta-adrenoceptor down-regulation is involved in the reduced positive inotropic effect of isoprenaline in SHR. Functional uncoupling of beta-adrenoceptors does not appear to be involved in the reduced beta-adrenoceptor-mediated positive inotropism in SHR. Binding studies do not show evidence for a large number of alpha-adrenoceptors coupling to a guanine-nucleotide binding protein in the rat heart. Finally, in ventricular myocardium of SHR, cardiac alpha-adrenoceptors do not serve as a reserve mechanism during impaired beta-adrenergic stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of Inotropic and Chronotropic Responses in Rat Isolated Atria and Ventricles

“…The al-adrenoceptor agonist, phenylephrine, produced significantly smaller maximal responses in both atrial and ventricular tissues than calcium chloride or the a-and PI-adrenoceptor agonist, noradrenaline. Similar results have been reported in left ventricular papillary muscles (Bohm et al 1988b) and atrial tissues (Wagner & Brodde 1978). Phenylephrine produced small chronotropic responses in rat right atria ( Fig.…”

Effects of Chronic Administration of Carteolol on .BETA.-Adrenoceptors in Spontaneously Hypertensive Rat Heart.

“…This finding is in agreement with several other reports (22)(23)(24). On the other hand, it has been reported that the number of cardiac fl-adrenoceptors in SHR is smaller than that in WKY (25)(26)(27). The reason for this discrepancy remains unknown.…”

Cardiovascular Changes During Maturation and Ageing in Male and Female Spontaneously Hypertensive Rats

“…SHRs have a selectively reduced responsiveness to norepinephrine and other adrenergic stimulation. 61 Furthermore, the development of heart failure, rather than hypertension or hypertrophy, may be the important step in the decreased responsiveness or increased toxicity to norepinephrine. 62 Intrinsic impairments of the nitric oxide system 32,63 together with elevated vascular oxidative stress 64,65 in SHRs would both contribute to the impairment of vascular relaxation responses seen in this study.…”