Emmanuel L. Bravo

Circulating and urinary catecholamines in pheochromocytoma. Diagnostic and pathophysiologic implications.

Three biochemical tests for the diagnosis of pheochromocytoma were evaluated in 24 patients with proved tumors and 40 patients whose clinical picture was suspect but who had no evidence of the disease. Measurement of resting, supine plasma catecholamines (by radioenzymatic assay) was more useful than either 24-hour urinary vanillylmandelic acid (VMA) or metanephrines or both. In only one of 23 patients with pheochromocytoma were plasma catecholamines within the range of those in patients without pheochromocytoma, as compared with urinary VMA in 11 of 22, urinary metanephrines in five of 22 and both metabolites in three of 22. These studies reaffirm the value of plasma catecholamines in the diagnosis of pheochromocytoma and indicate that urinary catecholamine metabolites are less useful. The poor correlation between the height of arterial pressure and circulating levels of catecholamines suggests that the regulation of arterial pressure in pheochromocytoma is complex.

Clonidine-suppression test: a useful aid in the diagnosis of pheochromocytoma.

THE diagnosis of pheochromocytoma is considered secure when typical signs and symptoms (e.g., hypertension, sweating, palpitation, and headaches) are associated with unequivocal biochemical evidenc...

Hyperkalemia in azotemic patients during angiotensin-converting enzyme inhibition and aldosterone reduction with captopril.

Thirty-three hypertensive patients with a wide range of renal function were studied during initiation of angiotensin-converting enzyme inhibition with captopril to evaluate changes in potassium levels concomitant with reduction of aldosterone excretion. Ten patients (Group I) with low levels of plasma renin activity had no change in either aldosterone excretion or potassium during the first week of therapy. Twenty-three other patients (Group II) had decreased aldosterone excretion of an average of 63 percent, often reversing secondary hyperaldosteronism. This was associated with a rise in serum potassium from 3.6 +/- 0.1 to 4.4 +/- 0.1 mEq/liter (p less than 0.001). Serum potassium levels during captopril therapy were inversely related to glomerular filtration rate (creatinine clearance) and transiently exceeded 6.0 mEq/liter in markedly azotemic subjects. Despite rising potassium levels, nine patients had reduced aldosterone excretion to subnormal levels, sometimes for many months. During initiation of converting-enzyme inhibition, potassium-sparing agents and supplements should be discontinued and serum potassium levels should be monitored closely, particularly in patients with imparied renal function.

β-Adrenergic Blockade in Diuretic-Treated Patients with Essential Hypertension

Abstract The influence of β-adrenergic blockade (160 mg per day of propranolol for four weeks) on plasma renin activity, plasma volume, and arterial pressure was explored in 20 patients with essential hypertension with hyper-reninemia from long-term diuretic therapy. In 15 of these patients renin activity remained elevated (range, 3.1 to 23.0 ng per milliliter). Plasma volume was unchanged in eight, increased in 11 and reduced in one. In 17 subjects mean arterial pressure decreased by more than 10 mm Hg, but these impressive reductions could not be explained by quantitative changes in either renin activity (r = 0.1) or plasma volume (r = 0.1). These data suggest that suppression of plasma renin activity by β-adrenergic blockade is not attainable during diuretic therapy and is not the major factor responsible for the antihypertensive action of propranolol. (N Engl J Med 292:66–70, 1975)

Hemodynamic and volume changes associated with captopril.

SUMMARY The effects of captopril on bemodynamic, rolmne, and neurohumoral indices were inrestigated in 33 patients with essential hypertension or renal arterial disease. Changes associated with treatment were studied under two conditions: immediately (V4 to 1 boar) after administration of the drug, or after 5 to 7 days of therapy. Blood pressure (BP) reduction in both conditions was due to a reduction in total peripheral resistance (TPR) (r = 0.714, p < 0.001 for A MAP / TPR); there was no significant change in either cardiac output or heart rate. The immediate BP and TPR responses were significantly related to pretreatment plasma renin activity (PRA) (r = 0.737, p < 0.001), but this correlation was much weaker (r - 0392, p > 0.50) after maintained treatment. Response to therapy could not be predicted from either bemodynamic or volume characteristics of the patients (r - 0.265, NS for A MAP / TBV and -0.262, NS for A MAP / cardiac output). There was no significant change in body weight during treatment, while plasma volume Increased slightly (+7% ± 2.8 SE, p < 0.05) but only in those patients who maintained a good BP response to captopril. Simultaneously, plasma aldosterone (PA) levels were reduced in relation to pretreatment level (r = 0.955, p < 0.001). Thus, whereas the hemodynamic pattern of response to captopril remained unchanged during therapy, its relationship to pretreatment PRA became progressively weaker. The clinical antihypertensive effectiveness of captopril was therefore not related to either humoral, hemodynamic, or volume characteristics of this group of patients. The unusual pattern of lack of significant plasma volume expansion during therapy might be related in part to sustained reduction of plasma aldosterone levels.

Regulation of Renal Hemodynamics and Glomerular Filtration in Patients with Renovascular Hypertension During Converting Enzyme Inhibition with Captopril

Changes in regional hemodynamics and function of the kidney during inhibition of angiotensin converting enzyme were studied in 25 patients with renovascular hypertension. A variety of patterns were observed depending upon (1) the activity of the renin-angiotensin system and concomitant administration of diuretics, and (2) the presence of bilateral renal artery stenosis. Increase in blood flow, glomerular filtration rate and sodium excretion during angiotensin blockade, in some instances, indicated tonic renal vasoconstriction before therapy. Release of the kidney from these effects may explain, in part, the sustained effectiveness of converting enzyme inhibition in chronic congestive heart failure. When compared with blood pressure reduction due to nitroprusside administration, initial captopril therapy in patients with unilateral stenosis produced a selective decrease in glomerular filtration, despite well-preserved renal blood flow. These results confirm the importance of efferent arteriolar vasoconstriction due to angiotensin II in man. Experimental studies demonstrate that angiotensin may become critical to sustaining glomerular filtration rate in the presence of stenosis during vasodilation. In patients with bilateral stenosis, this effect produces a syndrome of functional renal insufficiency. Taken together, these data demonstrate an intrarenal action of angiotensin II in human renovascular hypertension and underscore the importance of evaluating the functional impact of changes in regional hemodynamics.

Regulation of Sodium Balance in Hypertension

SUMMARY Pressure natriuresis, defined as the relationship between sodium excretion and mean arterial pressure (MAP), was assessed during graded reduction of arterial pressure with nltroprusside in 12 uncomplicated essential hypertensives. In all patients, sodium excretion fell linearly with reductions in arterial pressure (r > 0.71; p < 0.05). The percent change of sodium excretion from control per mm Hg change in MAP (AU N V/AMAP) was less in patients with resting MAP above 120 mm Hg than in those with lower BP (1.4% ± 0.1% versus 3.2% ± 0.3%; p < 0.001), but the pressure at which urine flow extrapolated to zero (77 ± 4 mm Hg) was not significantly different in the two groups. Further, there was a significant correlation between AU N V/AMAP and resting MAP (r = − 0.65, p < 0.05), suggesting that the sensitivity of pressure natriuresis was, in part, determined by the level of resting arterial pressure. This attenuation of pressure natriuresis might reduce sodium loss and thereby preserve body fluid volume in the face of persistent hypertension.

Transient renal dysfunction during initial inhibition of converting enzyme in congestive heart failure.

Treatment with captopril in resistant normotensive congestive heart failure is associated with a pronounced reduction in blood pressure, particularly after the first dose. The effects of this reduction on renal function were assessed in 10 patients at the beginning of and during chronic treatment (at one week and three months). Renal plasma flow and glomerular filtration rates were measured by isotope clearance during water diuresis. The first dose of captopril (25 mg) led to a pronounced fall in renal plasma flow and glomerular filtration rates together with a decrease in mean arterial pressure; this fall correlated with baseline plasma renin activity. These changes were paralleled by decreases in water and sodium excretion. In contrast, by the end of the first week of treatment a similar fall in mean arterial pressure occurred together with a pronounced increase in renal plasma flow; the glomerular filtration rate was maintained and there was no decrease in water and sodium excretion. This new response pattern recurred after three months of treatment. The difference in response at different stages of treatment may reflect the balance between the different mechanisms influencing kidney dynamics in heart failure and their alteration by converting enzyme inhibition. The sustained increase in renal plasma flow during chronic treatment with captopril may account for the continued control of heart failure in these patients.

Hypokalemia, in Bartter's Syndrome and Other Disorders, Produces Resistance to Vasopressors via Prostaglandin Overproduction:

Summary The role of hypokalemia and increased synthesis of prostaglandins in the decreased response of blood pressure to intravenous angiotensin II was studied in patients with Bartters syndrome and in patients with psychogenic vomiting. In patients with Bartters syndrome with high urinary prostaglandin E, treatment with an inhibitor of prostaglandin synthesis corrected the hyperreninemia and restored the pressor response to angiotensin II to normal but only partially corrected the hypokalemia. In patients with psychogenic vomiting with high urinary prostaglandin E, correction of the hypokalemia corrected the hyperreninemia and restored the pressor response to angiotensin II and to norepinephrine to normal. The findings suggest that hypokalemia, by stimulation of the synthesis of prostaglandin E in the kidney, produces hyperreninemia. An increase in synthesis of prostaglandin E in vascular tissue, stimulated by hypokalemia per se or by angiotensin II (produced by the hyperreninemia) or by both, increases the vascular resistance to angiotensin II and to norepinephrine.

Sodium, extracellular fluid volume, and cardiac output changes in the genesis of mineralocorticoid hypertension in the intact dog.

SUMMARY Twenty-four trained, conscious dogs with chronically implanted iliac catheters were used to assess the relative roles of sodium (Na) and volume in the development of mineralocorticoid hypertension. All were maintained on restricted Na diets; supplemental Na was given as slow I.V. infusions of 0.9% NaCl solution. The effect of gradual replenishment of total body sodium on arterial blood pressure (BP), cardiac output (CO), total peripheral resistance (TPR) and extracellular fluid volume (ECFV) was assessed at four separate levels of cumulative Na intake (70,140,420 and 840 mEq). The sequence of changes in 12 metyrapone-treated dogs was compared with 12 untreated controls submitted to the same protocol. Changes in fluid volumes and CO were virtually identical in the two groups; however, only dogs previously treated with metyrapone became significantly hypertensive (AMAP 16 and 28 mm Hg, p < 0.001). Within the metyrapone-treated groups, increases in volume and flow led to markedly different TPR responses dependent on level of cumulative sodium Intake; at levels