title: Vascular responsiveness to norepinephrine in sympathicotonic orthostatic intolerance.
abstract: Sympathicotonic orthostatic intolerance (hypotension, tachycardia, or both) is associated with normal or excessive orthostatic increases in plasma norepinephrine concentration and is reversible by the inflation of a military anti-shock trouser suit enveloping the lower limbs and abdomen. These facts suggest that one possible mechanism of the disorder might be a defect in alpha-adrenergic receptor or postreceptor responsiveness of the veins or arterioles. We have investigated in 11 patients and 15 healthy controls the blood pressure and heart rate responses to increasing rates of intravenous norepinephrine infusion (1 to 16 micrograms/min), the dorsal hand vein contractile responses to increasing rates of norepinephrine infusion (1 to 256 ng/min) with a linear variable differential transformer, and the platelet alpha 2-adrenergic receptor densities and dissociation constants. No statistically significant difference in any of these parameters was found between the normal subjects and nine of the 11 patients with orthostatic intolerance. The venous contractile response to norepinephrine was excessive in one patient and was virtually absent in another. Because supersensitivity of the hand veins to norepinephrine suggests up-regulation of alpha 2-receptors resulting from postganglionic autonomic insufficiency, this finding in one patient with sympathicotonic orthostatic hypotension might have been caused by venous denervation. The venous unresponsiveness to norepinephrine in the other patient presumably resulted from a defect in the venous receptors or smooth muscle function. It is evident that norepinephrine responsiveness and the innervation of the arterioles and hand veins was normal in the other nine patients, in whom the defect must have been mediated by some other mechanism.
authors.affiliation: Department of Medicine, State University of New York Health Science Center, Syracuse 13210.
authors.forename: J W
authors.initials: JW
authors.lastname: Miller
authors.forename: D H
authors.initials: DH
authors.lastname: Streeten
mesh_terms: D000293:Adolescent; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D004837:Epinephrine / Q000097:blood* / Q000502:physiology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D009422:Nervous System Diseases / Q000097:blood / Q000503:physiopathology*; D009638:Norepinephrine / Q000494:pharmacology*; D011187:Posture; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D015854:Up-Regulation
chemical_list: D011942:Receptors, Adrenergic, alpha; D009638:Norepinephrine; D004837:Epinephrine