Adrenaline increases the rate of cycling of crossbridges in rat cardiac muscle as measured by pseudo-random binary noise-modulated perturbation analysis.

Abstract

The mechanism of action of adrenaline on cardiac contractility in rat papillary muscles containing V1 and V3 isomyosins was analyzed during barium-activated contractures at 25 degrees C by frequency domain analysis using pseudo-random binary noise-modulated perturbations. The analysis characterizes a frequency (fmin) at which dynamic stiffness of a muscle is a minimum, a parameter that reflects the rate of cycling of crossbridges. We have previously shown that fmin for V1- and V3-containing papillary muscles were 2.1 +/- 0.2 Hz (mean +/- SD) (n = 10) and 1.1 +/- 0.2 Hz (n = 8), respectively, and that these values were independent of the level of activation. The present study's goal was to determine whether the inotropic action of adrenaline was associated with an increased rate of crossbridge cycling. The results show that a saturating dose of adrenaline increased fmin in V1 hearts by 49 +/- 2% (n = 11). The action on V3 hearts was significantly less; the increase in fmin was 26 +/- 2% (n = 6). The increase in fmin for V1 hearts was shown to be sensitive to the beta-blocking agent propranolol. These results suggest that adrenaline significantly increases the rate of crossbridge cycling by a beta-receptor-mediated mechanism. We conclude that the increased contractility of the heart in the presence of adrenaline arises not only from more complete activation of the contractile proteins but also from the increased rate at which each crossbridge can transduce energy.

Alterations in contractile properties and Ca2+ transients by beta‐and muscarinic receptor stimulation in ferret myocardium.

“…Iso (0 1 /LM) increased the frequency of dip to 3-25+0 10 Hz (N = 4) ( Figs 4B and 5A). These results are compatible with those of previous reports which suggested an increase in the CCR by ,-adrenoceptor stimulation (Hoh et al 1988;Berman et al 1988;Saeki, Shiozawa, Yanagisawa & Shibata, 1990). The addition of ACh (1 yM) restored the Iso-altered K. HONGO, E. TANAKA AND S. KURIHARA frequency of dip to the control level (2-75+0-13 Hz, N = 4) ( Figs 4C and 5A).…”

“…Alteration of the cross-bridge cycling rate in ,B-and muscarinic receptor stimulation Hoh et al (1988) showed an increase in CCR in rat ventricular muscle treated with adrenaline and suggested that an increase in CCR is a factor in faster contraction. In the present study, a similar perturbation method to that employed by Saeki et al (1978) was applied to a tonic contraction of tetanus to measure the CCR.…”

“…The temperature of the solution was kept at 30 'C. Peak-to-peak amplitude of force in response to length changes was measured and the frequency at which amplitude became a minimum (dip) was determined as the CC.R (Saeki et al 1978;Hoh et al 1988). …”

Effects of beta-adrenergic stimulation with dobutamine on isovolumic relaxation in the normal and failing human left ventricle.

“…In patients with severe CHF, both the inotropic3,47 and chronotropic19 responses to f8-adrenergic receptor stimulation are attenuated, presumably reflecting alterations in the /3-adrenergic receptor pathway that result in a deficient production of cAMP.15-7BeCaUSe cAMP also mediates the effect of ,B-adrenergic receptor stimulation to cause myocardial relaxation [8][9][10] Because an increase in heart rate per se can cause an increase in the rate of LV isovolumic relaxation,16,23,26 we felt it was important that heart rate be controlled by pacing during intravenous dobutamine infusion. Our data indicate that in normal subjects, a moderate (5 ,gg/kg/min) infusion rate of dobutamine that increases +dP/dt by 95% is associated with an approximately 18% decrease in r at a constant paced heart rate.…”

“…3,4 These abnormalities in systolic pump function are associated with reductions in ,B-adrenergic receptor densityl-3,5 and abnormal G-protein function,6 so uated production of cAMP.1 [5][6][7] cAMP also plays an important role in the regulation of myocardial relaxation. [8][9][10] The basal rate of LV isovolumic relaxation is prolonged in patients with CHF,1l-l3 and in vitro myocardium from patients with end-stage CHF exhibits prolongation of relaxation associated with a delayed fall in intracellular Ca2' concentration.14 Based on the preceding considerations, we hypothesized that the effect of f3-adrenergic receptor stimulation on the rate of LV isovolumic relaxation would be attenuated in patients with severe CHF. This hypothesis is supported by observations in dogs with LV failure after aortic banding15 but has not been tested in humans.…”