Greatly Enhanced Pressor Response to Antidiuretic Hormone in Patients with Impaired Cardiovascular Reflexes Due to Idiopathic Orthostatic Hypotension

Abstract

Pressor responsiveness to infused arginine-vasopressin (AVP), noradrenaline (NA), and angiotensin II (Ang II) of two patients with idiopathic orthostatic hypotension (Shy-Drager's syndrome) was compared with that of normal subjects. During the AVP infusion studies, plasma AVP concentrations were measured by radioimmunoassay. Compared to normal subjects, the two patients showed a greatly increased slope of the curves relating doses or plasma concentrations of AVP to blood pressure (BP) increases. While in the normal subjects an increase of plasma AVP up to 450 fmoles/ml (normal range, 0.5–5.0 fmoles/ml) raised BP only by 5–7 mm Hg, in the two patients an increase of plasma AVP within or slightly above the normal range increased BP by up to 40 mm Hg. During AVP infusion, heart rate fell in the normal subjects but did not change in the two patients. A 10 mm Hg increase in BP would require doses or concentrations of AVP about 1,000 times higher in normals than in the patients. Equipressor doses of Ang II or NA were only 2 to 8 times lower in patients than in normals. Thus, in individuals whose cardiovascular reflex activity is greatly reduced or absent, plasma AVP concentrations within the physiological range are vasopressor. We conclude that in normal subjects the vasopressor effect of intravenously infused AVP is greatly buffered by activation of cardiovascular reflexes. Since this phenomenon is not apparent to the same extent during Ang II or NA infusion, it seems possible that rising AVP plasma concentrations specifically increase the feedback gain of cardiovascular reflex systems.