Altered effect of BAY K 8644 after exposure of the rat aorta to IBMX or Db cAMP.

The development of isometric tension of aortic rings from rats was tested after cumulative administration of BAY K 8644 before and after exposure of the aortic preparations for 15 or 60 minutes to IBMX (10(-4) M) or Db cAMP (3.10(-4) M). BAY K 8644 exhibits dose-dependent contractions of those aortic rings which have not been exposed or have been exposed for only 15 minutes to IBMX or Db cAMP.

Decreased contractile response after exposure of the rat aorta to Db cAMP or IBMX.

Isometric tension developed by different receptor agonists was found to be decreased after pretreatment of rat aortic rings with IBMX or Db cAMP and only partially restored by CaCl2 and A 23187. The contraction produced by Bay k 8644 was converted into dose-dependent relaxation after pretreatment of the aorta rings with Db cAMP or IBMX. An alteration of the calcium channel is assumed to play a common role in the cAMP-dependent inhibition of the smooth muscle contraction.

Oscillation of cyclic AMP with the heart cycle of the canine myocardium in situ.

Oscillations of cyclic AMP with the cardiac cycle were demonstrated in the canine heart in situ. For tissue sampling an ECG(R-wave)-triggered, automatically working push-freeze-drill apparatus was employed which allowed intraventricular cryobiopsies from the left ventricular muscle of anaesthetized open-chest dogs. The nucleotide cyclic AMP oscillated with the cardiac cycle during normal working conditions, the higher cyclic AMP values occurring during systole.

Signal transfer in cardiac muscle. Alteration of the beta-adrenoceptor adenylate cyclase system in the hypertrophied myocardium.

The beta-adrenoceptor adenylate cyclase complex (beta ACR), located in the sarcolemmal membrane, is one of the most effective signal transduction systems regulating function and metabolism of heart muscle primarily via cyclic AMP. It is thought to play an important role in adaptive mechanisms of the heart as to pressure load and stressful stimuli. Present knowledge about composition and function of beta ARC enable us to clear up which of the single components of this system contributes to pathophysiological alterations of heart function.

Time parameters of contraction of inotropically responding cultured heart cells in relation to cellular cyclic AMP levels.

Television video microscopy combined with photoelectric recording was used to determine the influence of a number of positive inotropic agents on the amplitude (peak height) and the course of the contraction of electrically paced myocytes in 4-day monolayer cultures derived from the heart ventricles of 1 to 2-day old rats. Cyclic AMP was determined in parallel cultures of the same cell population. Reductions in time to 90% of peak height, 90% of relaxation time, and duration of contraction caused by peak height-augmenting concentrations of isoproterenol, epinephrine, dibutyryl cyclic AMP, and 1-methyl-3-isobutylxanthine, but not of theophylline, correlated with rises in cellular cyclic AMP levels.