Effects of isoprenaline, adrenaline and selective alpha 1- and alpha 2- adrenoceptor stimulation on hypoxic pulmonary vasoconstriction in rat isolated perfused lungs.
In the rat pulmonary vasculature perfused with blood in situ vasoconstriction induced by hypoxia was reversed by isoprenaline (doses greater than 1 ng) and adrenaline (doses greater than 30 ng) and exacerbated by phenylephrine but not UK 14304. Doses of adrenaline less than 30 ng had no effect, except in the presence of propranolol (1 microM) or phentolamine (3 microM) when they caused vasoconstriction and vasodilation respectively, showing that, at dose levels less than 30 ng, adrenaline's beta- adrenoceptor vasodilator properties were balanced by its alpha- adrenoceptor vasoconstrictor properties. The pressor effects of adrenaline, in the presence of propranolol, were antagonised by prazosin (0.1 microM) but not by equi-molar concentrations of rauwolscine. These results suggest that the alpha- adrenoceptor agonist property of adrenaline is of benefit to its use as an inhaled bronchodilator because unopposed beta- adrenoceptor stimulation can reverse hypoxic pulmonary vasoconstriction in poorly ventilated regions of the lung, promote further ventilation/perfusion mismatching and lower PaO2. They further suggest that adrenaline affects pulmonary vascular tone in the rat via alpha 1- adrenoceptors, stimulation of alpha 2- adrenoceptors having no effect.
Piercy
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V
Beecham Pharmaceuticals, Research Division, Epsom, Surrey, UK.
Smith
H
H
Arch
J R
JR
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D004837:Epinephrine / Q000494:pharmacology*; D005260:Female; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D008168:Lung / Q000098:blood supply / Q000187:drug effects*; D008297:Male; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D014661:Vasoconstriction / Q000187:drug effects*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D007545:Isoproterenol; D004837:Epinephrine