Increased sensitivity to noradrenaline in glucocorticoid-treated rats: the effects of indomethacin and desipramine.
Vascular responsiveness was evaluated in perfused mesenteric arteries from rats infused with dexamethasone (2 micrograms/day). Full dose-response curves to noradrenaline, vasopressin and potassium chloride were established. In order to investigate whether prostaglandins or noradrenaline uptake were involved in dexamethasone-induced pressor changes, vascular responses were compared before and during treatment with either indomethacin (a cyclo-oxygenase inhibitor) or desipramine (an inhibitor of neuronal catecholamine uptake). Dexamethasone-treated tissues showed an increased vascular sensitivity to noradrenaline compared with controls; the maximal response was greater and the concentrations of agonist required for a 50% response (EC50) was less in dexamethasone-treated tissues. The responses to vasopressin and potassium chloride were not affected. Systolic blood pressure in dexamethasone-treated rats was not significantly different from that in controls. Indomethacin infusion decreased the vascular responsiveness to noradrenaline in control and dexamethasone-treated rats to a similar degree. Noradrenaline responses after indomethacin treatment were not significantly different in control and dexamethasone-treated tissues. 6-Keto-prostaglandin-F1 alpha output during stimulation with noradrenaline was not affected by dexamethasone. Desipramine lowered pressor responses to noradrenaline at all concentrations and decreased the maximal response in tissues from dexamethasone-treated but not control rats. However, during infusion with desipramine, the EC50 for noradrenaline after dexamethasone was still less than in controls. Dexamethasone at low doses appears to selectively increase vascular sensitivity to noradrenaline in rats at a prehypertensive stage by changing prostaglandin synthesis and, possibly, neuronal uptake of noradrenaline.
Russo
D
D
MRC Blood Pressure Unit, Western Infirmary, Glasgow, UK.
Fraser
R
R
Kenyon
C J
CJ
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003891:Desipramine / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000139:chemically induced; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014655:Vascular Resistance / Q000187:drug effects*; D014667:Vasopressins / Q000494:pharmacology
D014667:Vasopressins; D011189:Potassium Chloride; D003907:Dexamethasone; D003891:Desipramine; D009638:Norepinephrine; D007213:Indomethacin