Differential regulation of right and left ventricular beta-adrenergic receptors in newborn lambs with experimental cyanotic heart disease.

To determine whether chronic hypoxemia secondary to an in- tracardiac right-to-left shunt alters regulation of the myocar- dial 63-adrenergic receptor/adenylate cyclase system, we pro- duced chronic hypoxemia in nine newborn lambs by creating right ventricular outflow obstruction and an atrial septal de- fect. Oxygen saturation was reduced to 65-74% for 2 wk. Eight lambs served as normoxemic controls. 13-receptor density (B.) and ligand affinity (KD) were determined with the radio- ligand '2"5iiodocyanopindolol and adenylate cyclase activity determined during stimulation with isoproterenol, sodium fluo- ride (NaF), and forskolin. During chronic hypoxemia, B.. decreased 45% (hypoxemic, 180.631.5 vs. control, 330.560.1 fmol/mg) in the left ventricle (exposed to hypox- emia alone) but was unchanged in the right ventricle (exposed to hypoxemia and pressure overload). KD was not different from control in either ventricle. Left ventricular isoproterenol- stimulated adenylate cyclase activity was decreased by 39% (30.04.3% increase vs. 44.19.5% increase) whereas right ventricular adenylate cyclase activity was unchanged. Stimula- tion of adenylate cyclase with NaF or forskolin was not differ- ent from control in either ventricle. Circulating epinephrine was increased fourfold whereas circulating and myocardial nor- epinephrine were unchanged. These data demonstrate a down- regulation of the left ventricular ,6-adrenergic receptor/adenyl- ate cyclase system during chronic hypoxernia secondary to an intracardiac right-to-left shunt. (J. Clin. Invest. 1990 . 85 :68- 74.) cyanotic heart disease -hypoxemia* myocardial fl-adrenergic receptor regulation creases heart rate and cardiac output and thus serves to main- tain systemic oxygen delivery (1, 2). During chronic hypox- emia, such as occurs in infants and children with cyanotic congenital heart disease, additional compensations, such as polycythemia, allow cardiac output to return to normal. There