Enhanced beta-adrenergic-receptor responsiveness in hypoxic neonatal pulmonary circulation.
The influence of alveolar hypoxia on pulmonary vascular adrenergic receptors was studied in conscious newborn lambs. In control animals, pulmonary vessels were directly constricted by epinephrine and norepinephrine, but were unaffected by isoproterenol. Pulmonary resistance (PVR) was also unaffected by propranolol, thus implying minimal beta-receptor activity under normoxic conditions. Hypoxia raised PVR but also modified the pulmonary vascular responses to catecholamines: isoproterenol became a dilator, whereas the constrictor effects of epinephrine and norepinephrine were abolished. Although beta-blockade did not alter base-line PVR, propranolol increased the constrictor response to hypoxia, implying that hypoxia increases beta-adrenergic activity or reactivity in the pulmonary circulation. Consistent with this hypothesis are the following: 1) in alpha-blocked lambs, epinephrine was without local effects during normoxia, but caused vasodilation during hypoxia; 2) the absent constrictor response to epinephrine during hypoxia is fully restored by propranolol; and 3) although alpha-blockade blunts the hypoxic constrictor response, the full response is restored when beta-blockade is added. These results indicate that the hypoxic constrictor response is partially opposed by increased beta-mediated vasodilation. These enhanced beta-receptor effects are due, at least in part, to increased beta-receptor reactivity of unknown mechanism.
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D000860:Hypoxia / Q000503:physiopathology*; D008168:Lung / Q000098:blood supply*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010643:Phenoxybenzamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011941:Receptors, Adrenergic / Q000503:physiopathology*; D011943:Receptors, Adrenergic, beta / Q000503:physiopathology*; D012756:Sheep; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects
D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D010643:Phenoxybenzamine; D011433:Propranolol; D009638:Norepinephrine; D004837:Epinephrine