EFFECTS OF DOPAMINE ON SINUS RATE AND VENTRICULAR CONTRACTILE FORCE OF THE DOG HEART in vitro AND in vivo

Abstract

1 Experiments were carried out on dog isolated papillary muscle and sinus node preparations perfused with arterial blood from a donor dog. The chronotropic and inotropic effects of dopamine were analysed by using reserpine, desmethylimipramine (DMI), cocaine and phenoxybenzamine, and the relative chronotropic and inotropic effects defined, the results being compared with those for noradrenaline (NA). 2 The effects of dopamine administered intra-arterially into the isolated preparations were reduced by pretreatment of animals with reserpine both in the papillary muscle and sinus node. The chronotropic effects, however, were affected less by pretreatment with reserpine than were the inotropic effects. 3 Desmethylimipramine (DMI) reduced the inotropic and chronotropic effects of dopamine, and enhanced the effects of NA and nerve stimulation; the chronotropic effects of the amines were less affected than the inotropic effects. 4 Cocaine enhanced considerably the inotropic and chronotropic effects of NA, and decreased the inotropic but not the chronotropic effect of dopamine. 5 Phenoxybenzamine enhanced the inotropic effects of dopamine, NA and nerve stimulation, but did not affect the chronotropic effects of the amines.6 When dopamine (1 to 300Mg/kg) was administered intravenously to the donor dog, it increased preferentially the contractile force of the ventricular myocardium with a comparatively small change of the sinus rate in the isolated preparations as well as in the heart in vivo. NA (0.1 to 10;Mg/kg) caused effects similar to those of dopamine. The maximal inotropic responses to these catecholamines were reached with lower doses than the chronotropic ones. 7 It is concluded that both the positive inotropic and the positive chronotropic responses to dopamine are mediated partially by a direct and partially by an indirect stimulant effect on p-adrenoceptors in the dog heart. The present results suggest that the difference in activity of dopamine and NA between the ventricular myocardium and the sinus node may be ascribed to the unequal innervation with adrenergic nerve fibres of the atrium and the ventricle (Furnival, Linden & Snow, 1971). The sinus node which is densely innervated by adrenergic nerve fibres may inactivate noradrenaline and dopamine more effectively than the ventricular myocardium through the uptake into the nerve and thereby be less sensitive to the exogenous catecholamines.

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

“…Blood-perfused papillary muscle and sinus node preparations Details of the experimental procedures for preparing the blood-perfused preparations have been given previously (Endoh, 1975). The anterior papillary muscle and the sinus node region were perfused by means of a peristaltic pump (separately, through the cannulated anterior septal artery and the sinus node artery, respectively) with arterial blood from a donor dog at a constant perfusion pressure of 100 mmHg.…”

“…Since it has been shown that the positive inotropic action elicited by stimulation of a-adrenoceptors in the mammalian heart depends very much on the experimental conditions (Nakashima et al, 1973;Endoh & Schumann, 1975a;Endoh, et al, 1975;Ledda et al, 1975;Mugelli et al, 1976;Kunos, 1977;Kunos & Nickerson, 1977), in this study the ventricular myocardium and sinus node of the dog were maintained under near physiological conditions (Endoh, 1975) by perfusing with arterial blood from a donor dog. The actions of PE were then compared with those of Iso.…”

“…His observations Peon, Cros & Mendez (1969) noted that phenylhave been confirmed in rat (Nakashima, Tsuru & Shi-ephrine responses were inhibited by propranolol. In gei, 1973) and rabbit (Parr & Urquilla, 1972;Benfey, the present experiments the isolated blood-perfused papillary muscle (Endoh, 1975) and isolated ventricular strips from the dog were used in order to clarify this problem. The influence of temperature, stimulation frequency, phosphodiesterase inhibition and of a-and f-adrenoceptor blocking agents on phenylephrine-induced myocardial stimulation were investigated.…”

Signal Transduction and Ca2+ Signaling in Intact Myocardium

“…In addition, it has been shown that other functional proteins such as myosin binding protein C and NCX are phosphorylated to potentially contribute to the regulation of Ca 2+ handling (11,12). Most sympathomimetic amines such as phenylephrine (20,23,24), dopamine (21,46), norepinephrine, epinephrine (46), isoproterenol (22), dobutamine (25), and denopamine (26) ] o (9). This may be partly due to a decrease in myofilament Ca 2+ sensitivity in relation to troponin I phosphorylation and abbreviation of Ca 2+ transients due to activation of SERCA2a.…”

Inotropic, Chronotropic, and Arrhythmogenic Effects of Dopamine on the Isolated Working Heart of Rabbit

“…To clarify whether these inotropic effects of DA as well as the chronotropic ones are direct actions on the cardiac muscles or indirect ones by releasing noradrenaline (NA) from the sympathetic nerve terminals in the cardiac muscles, the sympathetically denervated preparations by the treatments with reserpine [7][8][9][10][11][12] or 6-hydroxydopamine (6-OHDA) [13][14][15] were used, as reported previously. To the author's knowledge, it remains unknown whether the arrhythmogenic effects of DA could be produced by the direct or indirect actions.…”