CARDIAC BETA-ADRENOCEPTOR-EFFECTOR COUPLING IN PORTAL VEIN-STENOSED RATS

Cardiac beta-adrenergic signal transduction was examined in chronic po rtal vein-stenosed rats. Basal tension and maximum rate of tension dev elopment were significantly depressed in left ventricular papillary mu scles (0.21 +/- 0.03 N/cm(2) and 8.2 +/- 1.7 N.s(-1).cm(-2), respectiv ely) compared with sham-operated controls (0.51 +/- 0.05 N/cm(2) and 1 9.9 +/- 4.4 N.s(-1).cm(-2), respectively). The positive inotropic resp onse to isoproterenol was also attenuated. Adenosine 3',5'-cyclic mono phosphate formation was decreased significantly when GTP (-41.9%), iso proterenol with GTP (-45.3%), or guanosine 5'-O-(3-thiotriphosphate) ( -52.4%) was used to stimulate adenylyl cyclase, but not when Mn2+ or f orskolin was used. beta-Adrenoceptor density (sham operated 24.6 +/- 2 .0 fmol/mg; portal vein stenosed 26.4 +/- 2.1 fmol/mg) and the apparen t dissociation constant (sham operated 0.26 +/- 0.04 nM; portal vein s tenosed 0.29 +/- 0.04 nM) were unaffected. Portal venous hypertension did not alter beta-adrenergic receptor affinity for isoproterenol. How ever, it was necessary for isoproterenol to occupy three times the num ber of receptors in papillary muscles from stenosed animals to produce an equal increase in force generation. These data suggest that althou gh portal vein stenosis does not alter cardiac beta-adrenoceptor densi ty or affinity for ligands, transduction of the signal between the rec eptor and adenylyl cyclase is adversely influenced and may be responsi ble for the diminished responsiveness of beta-adrenoceptors in the myo cardium.