Differentiation of cardiac chronotropic and inotropic effects of ?-adrenoceptor agonists

Abstract

The relative inotropic and chronotropic activity of beta-adrenoceptor agonists was studied in the noradrenaline-depleted, anaesthetized cat. Terbutaline, a selective beta2-adrenoceptor agonist, gave at a certain dose a more pronounced chronotropic than inotropic response, while a new beta1-selective adrenoceptor agonist (-)-H 80/62 produced the same degree of chronotropic and inotropic stimulation. The results indicate that there is some difference between the beta-adrenoceptors in the sinus node mediating chronotropic stimulation and beta-adrenoceptors in the ventricular myocardium mediating stimulation of the contractile force. It has been shown that there are both beta1- and beta2-adrenoceptors in the heart (Carlsson et al., 1972). In the light of this finding it is hypothetized that there are differences in the relative distribution of beta1- and beta2-adrenoceptors in the sinus node and in the myocardium. Athough beta1 is the predominant type of beta-adrenoceptor in both regions, the beta1:beta2 concentration ratio seems to be higher in the myocardium, than in the sinus node.

PROCEEDINGS OF THE British Pharmacological Society 4th–6th April, 1979

“…Our data thus support the findings from in vivo experiments in cats (Carlsson et al, 1977) suggesting a heterogenous P-adrenoceptor population in the heart and a regional distribution of the two subtypes that differs between the sinus node region and the ventricular myocardium.…”

“…The organ specific subheterogeneity of f-adrenoceptors proposed by Lands, Arnold, McAuliff, Luduena & Brown (1967) has been subjected to criticism during the last decade (Carlsson, Ablad, Brandstrom & Carlsson, 1972;Zaagsma & Oudhof, 1976 and the ventricular myocardium of cat heart (Carlsson, Dahlof, Hedberg & Tangstrand, 1977).…”

The guinea‐pig isolated bronchus for the in vitro study of small calibre airway reactivity

“…Evidence for this was provided by the lack of activity of prenalterol, a specific PI-adrenoceptor stimulant (Carlsson et al, 1977), and by comparing the ECQ0 values for isoprenaline and fenoterol with that for noradrenaline (NA). Isoprenaline and fenoterol were 27 and 180 times, respectively, more active in the bronchus than NA, whereas in the isolated guinea-pig trachea, the isoprenaline: NA and fenoterol: NA ratios are 10 and 20 respectively (Carlswell & Nahorski, 1983).…”

Hemodynamic effects of prenalterol in patients with ischemic heart disease and congestive cardiomyopathy.

“…Typical left ventricular end-diastolic and end-systolic silhouettes before and after prenalterol are illustrated in figure 1. Mean end-diastolic and end-systolic volumes decreased after prenalterol.…”