Excessive gravitational blood pooling caused by impaired venous tone is the predominant non-cardiac mechanism of orthostatic intolerance.

1. In a group of 40 patients with orthostatic intolerance due to hypotension and/or tachycardia, we have compared the pathogenetic roles of impaired contractility of the arterioles and the veins by measuring contractile responsiveness of the arterioles, reflected by increases in diastolic blood pressure and of the veins reflected by measurements of reduction in venous diameter during intravenous noradrenaline infusions. 2. Compared with 27 healthy subjects, patients with diffuse autonomic insufficiency showed striking supersensitivity in diastolic blood pressure (six out of eight) and venous constrictive responses (seven out of eight patients) to noradrenaline, consistent with impaired arteriolar and venous innervation. 3. In contrast, the patients with hyperadrenergic orthostatic hypotension (n = 16) and orthostatic tachycardia (n = 16) showed diastolic blood pressure responses to noradrenaline that were almost invariably within the 95% confidence limits of the changes in normal subjects but supersensitive constrictive responses of foot veins in 22 of 32 subjects and subnormal venous responses in two individuals. The rate of noradrenaline infusion calculated to cause 50% of maximal venous constriction (the ED50) was significantly lower in the patients [mean (SEM) 6.8 (1.9) ng/min] than in the normal subjects [mean (SEM) 23.2 (3.0) ng/min, P < 0.025]. 4. The finding of significantly supersensitive foot vein constrictive responses to noradrenaline infusion in the patients of all three groups and supersensitive blood pressure responses exclusively in the patients with diffuse autonomic insufficiency indicates that venous pooling in the legs was the predominant pathogenetic mechanism of orthostatic intolerance in all three types of patients studied. 5. Correction of the orthostatic hypotension and/or tachycardia by external compression in virtually all patients confirmed this conclusion.