Gunnar H. Anderson

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 micrograms/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 alpha-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 were supported by the finding that the orthostatic changes were corrected by lower body compression to 45 mm Hg with a MAST pressure suit.

Renin angiotensin involvement in transient hypertension after renal injury.

Transient hypertension occurred in 3 patients shortly after blunt injury to the abdomen. Renal trauma was suspected in all 3 patients and radiological evidence for renal injury was present in 2. Plasma renin activity definitely was elevated in 1 patient and probably was elevated in another. There was a decrease in blood pressure in all 3 patients during infusion of the angiotensin II analogue--saralasin--showing that the hypertension in these patients was angiotensin-mediated. Renal function as reflected by the blood urea nitrogen, creatinine and electrolytes was not impaired significantly. Thus, acute hypertension after blunt abdominal trauma may be angiotensinogenic and is not necessarily sustained.

Hypertension: relating drug therapy to pathogenetic mechanisms.

Hypertension is not a single disease. It is a disorder of cardiovascular physiology which may result from a large variety of causes — known and unknown — and may be the consequence of several distinct pathogenetic mechanisms. Since the causes and the pathogenesis of hypertension are not always the same, it is reasonable to believe that optimal therapy should not always be the same and that treatment should be aimed, as far as possible, at correcting the specific etiology or pathogenetic mechanism that is present in each individual. Our gradually developing understanding of the physiological derangements leading to hypertension, coupled with the availability of steadily increasing numbers of new drugs with known mechanisms of action, offers improved opportunities to match the drug used with the defect that is responsible for the hypertension.