PARADOXICAL β RECEPTOR MEDIATED VASOCONSTRICTION IN THE STAGE 24 CHICK EMBRYO

Abstract

Little is known about neurohumoral control of the embryonic cardiovascular system. We studied the effect of increasing intravenous doses of isoproterenol, epinephrine and norepinephrine on heart rate (HR), mean dorsal aortic blood flow (Q)), mean vitelline artery pressure (P) and vascular resistance (R) in the stage 24 (4 day) chick embryo. Dorsal aortic blood velocity was measured with a 20 MHz pulsed-Doppler velocity meter. Pressure was measured with a servo null pressure system. β receptor properties were determined using radioligand binding and β agonist stimulated adenylate cyclase activity on vitelline vascular bed broken-cell preparation. Isoproterenol > epinephrine > norepinephrine caused a dose related decrease in Q, an increase in R but no change in HR or P. These effects were blocked by propranolol but unaffected by phenoxybenzamine. Radioligand binding was characteristic of a β receptor with a KD for [125I] Iodocyanopindolol of 10±3 pM and a receptor density of 139±8 fmol/mg protein. Isoproterenol increased adenylate cyclase activity 55%±6% from baseline values. These data are consistent with a β receptor which stimulates adenylate cyclase activity and mediates paradoxical vasoconstriction. Since isoproterenol causes vasodilatation in mature embryos, we speculate β receptor function changes with development.