Sympathetic tone and pressor response to noradrenaline during mineralocorticoid-induced blood pressure rise in man.
To gain insight into the role of the sympathetic nervous system in the development of mineralocorticoid hypertension, we determined noradrenaline and adrenaline in plasma and urine before, during and after administration of the synthetic steroid, fludrocortisone, for a period of 6 weeks in normotensive volunteer subjects. In addition, pressor reactivity to exogenous noradrenaline, platelet alpha 2- and lymphocyte beta 2-receptors, and platelet intracellular free calcium were determined. Fludrocortisone induced a fall in free and sulpho-conjugated plasma noradrenaline and after 6 weeks, a rise in free and sulpho-conjugated noradrenaline excretion. The number of alpha 2- and beta 2-adrenergic binding sites decreased. A marked increase in platelet free intracellular calcium was found after the first week of fludrocortisone administration followed by a decrease in the following weeks. Reactivity to exogenous noradrenaline was found to be enhanced and this could be a factor contributing to the development of hypertension. Whereas the decrease in plasma noradrenaline observed would suggest a diminution in sympathetic tone, the finding of a rise in urinary noradrenaline excretion after 6 weeks of steroid administration in the presence of suppressed plasma levels points to an increased renal sympathetic drive. The decreased number of platelet alpha 2- and lymphocyte beta 2-receptors observed would also be consistent with the assumption of an increased sympathetic tone.
D000328:Adult; D001792:Blood Platelets / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000097:blood; D004837:Epinephrine / Q000378:metabolism; D005438:Fludrocortisone / Q000494:pharmacology; D006801:Humans; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D008901:Mineralocorticoids / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism* / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D013431:Sulfates / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects*
D008901:Mineralocorticoids; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D013431:Sulfates; D002118:Calcium; D005438:Fludrocortisone; D009638:Norepinephrine; D004837:Epinephrine