Our investigations were aimed at characterizing of myocardial receptor-systems and their changes in right ventricular hypertrophy (RVH) and right ventricular failure (RVF), respectively, using the monocrotaline-(MCT) rat modell. Four to six weeks after administering the MCT alcaloid, the β-adrenoceptor (β-AR)-G-protein-adenylyl cyclase-(AC)-system was significantly diminished in right ventricular membrane preparations. Compared with RVH changes were more pronounced in rats with RVF: β-AR density as well as the number of β-AR prevailing in a "high affinity state" were reduced, G-protein-coupled receptor kinase activity was markedly enhanced in cytosolic and membrane preparations and GS-protein content was attenuated. The activity of the catalytic unit of AC was diminished, hence AC stimulation by isoprenaline, GTP, NaF and Forskolin was significantly reduced. Similiar alterations were observed in left ventricular preparations, though changes were less pronounced. While investigating β-AR density and isoprenaline-stimulated cAMP accumulation in cardiomyocytes isolated from either ventricles, significant attenuations were observed in right ventricular cardiomyocytes exclusively. Consequently, there was an impressive reduction in the positive inotropic effect of isoprenaline on right and left ventricular muscle stripes. Muscarinic receptors, coupling to AC by inhibitory G-proteins, were unchanged in right ventricles. However, there was a significant enhancement of those receptors detectable in left ventricles of RVF rats. In right ventricular tissue slices (RVH and RVF), further experiments showed a diminished uptake1 density and activity. These changes, again, were more prominent in tissue slices of RVF animals. On the other hand, in left ventricles, uptake1 activity only was significantly attenuated in rats with RVF. Constituting another signalling system, α1-AR density as well as their coupled Gq/11-proteins were markedly reduced in either ventricles of MCT-treated animals with more pronounced alterations for rats with right heart failure (RVF). For this reason, noradrenaline-induced positive inotropic effect in the presence of propranolol were attenuated on right and left ventricular muscle stripes. The density of the Gq/11-protein coupled endothelin receptors, on the contrary, was exlusively enhanced in right ventricular membrane preparations of RVF as was the endothelin-induced positive inotropic effect. Neither of those changes were detected in left ventricles. |