Influence of beta-adrenoceptor antagonists on spontaneous rate and on force of contraction of isolated rabbit atria.

The influence of beta-adrenoceptor antagonists on the spontaneous rate and on force of contraction of the myocardium was studied independently on spontaneously beating right and electrically driven isolated left atria of rabbit. On spontaneous rate, practolol had sympathomimetic effect only, N-isopropylmethoxamine (IMA), had both sympathomimetic as well as depressant effects, whereas alprenolol, procinolol, bunolol and H 35/25 had depressant effects only in higher concentrations. The order of potency was procinolol greater than bunolol greater than alprenolol greater than H 35/25 greater than and IMA. On the contractions of isolated left atria, all beta-adrenoceptor antagonists produced concentration-dependent depressant effect. In relation to procinolol, these agents were 5-125 times less potent for depressing the contractions of left atria by 15% and the order of beta-potency was procinolol greater than alprenolol greater than bunolol = H 35/25 greater than IMA greater than and practolol. The present results indicate that the depressant effects of beta-adrenoceptor antagonists on spontaneous rate of right atria and on contraction of isolated left atria are not related to each other.

Adrenergic receptors in the hypothalamus concerned with control of arterial blood pressure: elicited by electrical and chemical stimulation.

The study was made with the help of a chemitrode placed in various areas of the hypothalamus by the stereotaxic technique, for electrical and chemical stimulation (noradrenaline or isoprenaline) before and after microinjection of respective blockers (phenoxybenzamine or practalol). The results indicated the presence of both alpha and beta-adrenoreceptors in the anterior and dorsomedial hypothalamus producing a depressor response, and, the presence of alpha adrenoreceptors in the posterior and lateral hypothalamus producing a pressor response.

A mechanism of action of phenylephrine on heart.

Phenylephrine exerted a positive chronotropic and inotropic effect on isolated, spontaneously beating, atria of reserpinised rabbits. Addition of phenoxybenzamine and phentolamine resulted in a depression of control contractile amplitude. Practolol, however, was devoid of this effect. The positive inotropic response to phenylephrine was significantly antagonised by all the three blockers used, while positive chronotropic response was annulled by phentolamine and practolol, but not with phenoxybenzamine. It is, therefore, suggested that phenylephrine exerts its cardiostimulant effects through mediation of both alpha and beta-1 adrenoceptors. A probable mechanism of action could be, that phenylephrine acts on some specific chemical group, shared by alpha and beta1 receptors. This specific group is probably blocked by both alpha and betaceptor antagonists separately, so phenylephrine becomes ineffective in presence of these antagonists.