Characterization of Adrenoceptors Mediating Positive Inotropic Responses in the Ventricular Myocardium of the Dog

Abstract

1 The pharmacological characteristics of adrenoceptors mediating the positive inotropic action in the dog heart were assessed by the use of blood-perfused papillary muscles and isolated strips of ventricular myocardium. 2 On the blood-perfused papillary muscle driven at 2 Hz and in sinus node preparations, phenylephrine induced positive inotropic and chronotropic responses in the same dose range and was much less potent than isoprenaline. The dose-response curve for the chronotropic action of phenylephrine was parallel to that of isoprenaline, whilst the dose-response curve for the inotropic action of phenylephrine was less steep than that of isoprenaline.3 The infusion of pindolol, a P-adrenoceptor blocking agent, at a rate of 1 1±g/min, shifted the isoprenaline dose-response curves to the right, and to the same extent, in both papillary muscle and sinus node preparations. In contrast to isoprenaline, the antagonism of phenylephrine by pindolol was noncompetitive. Phentolamine did not affect the positive inotropic and chronotropic actions of phenylephrine. 4 On isolated ventricular strips a-adrenoceptor blockade by 10-6M phentolamine did not affect dose-response curves to phenylephrine or dopamine. Pindolol shifted the dopamine dose-response curves to the right in a competitive manner and those of phenylephrine in a noncompetitive manner. 5 On ventricular strips from reserpine-pretreated dogs phenylephrine and tyramine dose-response curves were shifted markedly to the right and downwards. Desipramine (10-5M) which enhanced the action of noradrenaline considerably reduced the myocardial responses of phenylephrine.6 Papaverine (10' M) decreased the threshold concentration of phenylephrine required to stimulate the myocardium and shifted phenylephrine dose-response curves to the left. 7 Raising the temperature from 32°C to 37°C shifted phenylephrine dose-response curves to the right; when the temperature was raised from 37°C to 42°C the affinity of the drug was not changed.8 Other a-adrenoceptor stimulants, methoxamine and clonidine, decreased the active tension of ventricular strips. The responses to noradrenaline and adrenaline (in the presence of pindolol; 3 x 10-'M) were not affected by phentolamine (10-6 M).9 The results indicate that adrenoceptors mediating positive inotropic responses in the dog ventricle are of the P-type and that post-synaptic a-adrenoceptors are not involved. Phenylephrine acts mainly by releasing noradrenaline from adrenergic nerve endings and partly by a weak direct action on ,B-adrenoceptors.

The Influence of Hormonal and Neuronal Factors on Rat Heart Adrenoceptors

“…In agreement with previous observations (Govier, 1968) (Endoh, Shimizu & Yanagisawa, 1978); (+ -propranolol, which is devoid of f-blocking activity in similar concentrations, did not significantly alter the phenylephrine response. The above observations indicate an increase in the !-and decrease in the #-component of cardiac adrenoceptor responses after hypophysec-_*-~tomy or during treatment of hypophysectomized rats observed earlier in atria of thyroidectomized rats (Kunos, 1977).…”

Sustained negative inotropism mediated by α‐adrenoceptors in adult mouse myocardial developmental conversion from positive response in the neonate

“…As for the subclassification of receptor types, recent papers suggest the existence of additional types of a-adrenoceptors (Noguchi et al, 1993) Fedida, 1993;Terzic et al, 1993). In the myocardium of the rat (Tohse et al, 1987), cat (Hartmann et al, 1988) and rabbit (Skomedal et al, 1990), x-adrenoceptor stimulation results in increases in contractile force, while in that of the dog (Endoh et al, 1978), guinea-pig (Hescheler et al, 1988) and ferret (Endoh et al, 1989), inotropic effects are small or do not exist. Varying results have been reported with human myocardium (Jakob et al, 1988;Osnes et al, 1989 (Tohse et al, 1987).…”

Signal Transduction and Ca2+ Signaling in Intact Myocardium

“…α-Adrenoceptor-mediated positive inotropic effects show a wide range of species-dependent variation (54,55,60). They are pronounced in the rabbit (45,50); moderate in rat, guinea pig, and monkey (49); least in the ferret (52); and absent in dog ventricular myocardium (47,48,63). In single mouse ventricular myocytes, α-adrenoceptor stimulation decreases Ca 2+ transients and cell shortening (64).…”