Hyperthyroidism induces supersensitivity to biogenic amines in rat vascular tissue via a pre- and a postjunctional mechanism.
The effect of hyperthyroidism was investigated on the sensitivity of rat aortic and mesenteric arteries to the contractile effects of biogenic amines, K+ and Ca++. Supersensitivity to norepinephrine, methoxamine and clonidine was observed in the mesenteric artery. Methoxamine and clonidine are immune to disposition by neuronal and extraneuronal uptake, and supersensitivity to norepinephrine persisted in the presence of hydrocortisone and desmethylimipramine, suggesting that the supersensitivity was postjunctional in origin. In addition, reserpine pretreatment induced supersensitivity to norepinephrine in control mesenteric arteries, but in hyperthyroid mesenteric arteries no further increase in sensitivity was observed after reserpine pretreatment supporting a postjunctional mechanism. In the aorta, a small increase in sensitivity was observed to norepinephrine, no supersensitivity was detected to methoxamine and supersensitivity to norepinephrine was not apparent in the presence of hydrocortisone, suggesting a prejunctional mechanism. The existence of a small prejunctional component in the mesenteric artery also was indicated, as incubation with hydrocortisone attenuated the degree of supersensitivity after thyroid hormone pretreatment. In the mesenteric artery, postjunctional supersensitivity also was observed to 5-hydroxytryptamine. However, no increase in sensitivity was observed to KCl or CaCl2 suggesting that the postjunctional supersensitivity was not due to an increase in the sensitivity of the contractile apparatus, and was specific for receptor-mediated effects of agonists.
Grassby
P F
PF
Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
McNeill
J H
JH
D000818:Animals; D001679:Biogenic Amines / Q000494:pharmacology*; D003891:Desipramine / Q000494:pharmacology; D006854:Hydrocortisone / Q000494:pharmacology; D006980:Hyperthyroidism / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012110:Reserpine / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*
D001679:Biogenic Amines; D012701:Serotonin; D011189:Potassium Chloride; D012110:Reserpine; D008729:Methoxamine; D003891:Desipramine; D006854:Hydrocortisone; D009638:Norepinephrine