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)
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