Demonstration in human atrial preparations of ?-adrenoceptors mediating positive inotropic effects

Abstract

In isolated, electrically driven right auricular strips of the human heart the inotropic effect of phenylephrine was studied. 1. First, the influence of the driving rate on the tension developed (i.e., the frequency-force relationship) was determined by stimulation of the preparations at 0.1, 0.5, 1, 2 and 3 HZ. The force of contraction was lowest at a stimulation rate of 0.1 HZ (36.9 g/g dry weight). The maximally developed force of contraction observed at frequencies of 0.5, 1 and 2 HZ amounted to about 200 g/g dry weight. The values did not significantly differ from each other. 2. The negative log of the EC50 (-log EC50) for the positive inotropic effect of phenylephrine determined at a frequency of 0.5 and 1.0 HZ amounted to 5.28 +/- 0.08 and 5.34 +/- 0.11, respectively. The alpha-adrenolytic drug phentolamine (3 x 10(-6) M) diminished significantly the -log EC50 to 5.01 +/- 0.04 and 4.89 +/- 0.10, respectively. 3. At a frequency of 1 HZ a shift of the concentration-response curve to the right was observed after treatment with the beta-adrenolytic drug pindolol (3 x 10(-8) M); the -log EC50 of phenylephrine decreased significantly to 4.08 +/- 0.07. 4. From these results it is concluded that alpha-adrenoceptors are present in human atria; they mediate positive inotropic effects and are stimulated by phenylephrine.

Selective and full β1‐adrenoceptor agonist action of a catechol derivative of denopamine (T‐0509) in the guinea‐pig cardiac muscle and trachea: comparison with denopamine, xamoterol and isoprenaline

“…Noradrenaline is a pI-selective agonist with potent a-adrenoceptor agonist activity, and this activity has been reported to induce positive inotropic action (Schumann et al, 1978;Bruchner et al, 1984) and cardiac hypertrophy (Simpson, 1985). Recently, P2-adrenoceptors in the human heart have been found to couple to adenylate cyclase and to mediate positive inotropic and chronotropic actions (Gille et al, 1985;Kaumann & Lemoine, 1987).…”

Reduced α1‐ and β2‐adrenoceptor‐mediated positive inotropic effects in human end‐stage heart failure

“…This discrepancy may be explained by the preparations used in the respective studies. Schumann et al (1978) investigated atrial tissue. In previous reports from our laboratory, tissue from less severely failing hearts was studied Schmitz et al, 1987 positive inotropic effect in end-stage heart failure.…”

Actions of sympathomimetic amines on the Ca2+ transients and contractions of rabbit myocardium: reciprocal changes in myofibrillar responsiveness to Ca2+ mediated through alpha- and beta-adrenoceptors.

“…10 -36 The same explanation would account for the observation that the maximal inotropic effect of a-adrenoceptor stimulation is more susceptible than that of/3-receptor stimulation to alteration by experimental variables such as changes in temperature or stimulation frequency or to inhibition by calciumentry blocking drugs. 10 Although a-adrenoceptors stimulation does produce a significant positive inotropic effect in human atrial 80 -*' and ventricular 82 muscle, the effect is not large, and it is obvious that a-agonists cannot be used therapeutically for their inotropic effects because of their multiple actions elsewhere in the body. This does not mean, however, that the fundamental mechanism underlying their inotropic action has no therapeutic promise.…”