Hypoxic contraction of isolated canine coronary artery. Mediation by potassium-dependent exocytosis of norepinephrine.
Effects of hypoxia on arterial tone, efflux of potassium, and efflux of norepinephrine were monitored for isolated canine coronary arteries labeled with radioactive potassium (42K) and norepinephrine (3HNE). Hypoxia elicited transient relaxation and subsequent sustained contraction accompanied by marked increases in the effluxes of 42K and 3HNE. After sympathetic nerve injury with 6-hydroxydopamine or cold storage, arteries responded to hypoxia with sustained relaxation. Sustained relaxation occurred also after pretreatment with L-propranolol, but not with D-propranolol or phentolamine. Inhibition of hypoxic contraction by L-propranolol did not alter 42K or 3HNE efflux. Colchicine, an inhibitor of the exocytosis of NE, suppressed hypoxic 3HNE efflux and contraction, but not 42K efflux. Proadifen inhibited 42K and 3HNE efflux as well as contraction. During proadifen-inhibited 42K efflux, exogenous K+ augmented overflow of 3HNE, indicating that proadifen relaxed the hypoxic artery primarily by inhibiting K+-dependent exocytosis of NE. The ratio of NE to dopamine beta-hydroxylase activity was similar in effluents from oxygenated arteries exposed to elevated K+ concentrations and in effluents from hypoxic arteries. Thus, hypoxia evoked exocytotic release of norepinephrine which promoted contraction by a beta-adrenergic mechanism.
D000332:Aerobiosis; D000818:Animals; D003078:Colchicine / Q000494:pharmacology; D003331:Coronary Vessels / Q000503:physiopathology*; D004285:Dogs; D004299:Dopamine beta-Hydroxylase / Q000378:metabolism; D005089:Exocytosis / Q000187:drug effects; D005260:Female; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009638:Norepinephrine / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology; D011941:Receptors, Adrenergic / Q000187:drug effects; D014439:Tyramine / Q000494:pharmacology
D011941:Receptors, Adrenergic; D011433:Propranolol; D004299:Dopamine beta-Hydroxylase; D011188:Potassium; D003078:Colchicine; D009638:Norepinephrine; D014439:Tyramine