Mechanisms of orthostatic hypotension and tachycardia in patients with pheochromocytoma

We have explored the pathophysiological mechanisms of orthostatic hypotension and orthostatic tachycardia, found to be present in 83% and 61% respectively of 18 patients with subsequently proven pheochromocytoma. Orthostatic increases in plasma norepinephrine (NE) concentrations were significantly greater in the patients than in normal control subjects. Intravenous infusions of NE at 1, 2, 4, 8, and 16 μg/min induced similar increases in plasma NE levels but smaller increments in systolic and diastolic BP in the pheochromocytoma patients than in normal control subjects. This was reflected by a significantly greater increment in plasma NE concentration required to raise systolic BP by 15 mm Hg and diastolic BP by 7 mm Hg in the pheochromocytoma patients than in the normal subjects (P< .05 and P< .01, respectively). Measurements of venous contractile responses to locally infused NE by the dorsal hand vein (LVDT) technique revealed significantly reduced slopes of the regressions of log NE infusion rate on change in venous diameter in the pheochromocytoma patients compared with normal subjects. The results indicate reduced responsiveness of the vasculature to NE in patients with pheochromocytoma, probably due to down-regulation of α-adrenergic receptors resulting from persistent elevation of the physiological agonist NE. This was shown by other authors to be present in circulating platelets. The pathophysiological importance of the subnormal venous responses to the orthostatic hypotension and tachycardia in the patients was supported by the finding that the orthostatic changes were corrected by lower body compression to 45 mm Hg with a MAST pressure suit.