Paul I. Jagger

Abnormal Responsiveness of the Renin Aldosterone System to Acute Stimulation in Patients with Essential Hypertension

Abstract The responsiveness of the renin aldosterone system to acute stimulation was determined in 16 patients with essential hypertension and 12 normotensive volunteers. All patients were studied ...

The 48-Hour Adrenocorticotrophin Infusion Test for Adrenocortical Insufficiency

Abstract A new continuous adrenocorticotrophic hormone (ACTH) infusion test for 24 or 48 hr can accurately distinguish between normal adrenocortical function, primary adrenocortical insufficiency, ...

Physiologic responses of the transplanted human kidney.

Abstract The denervated, transplanted kidneys of six patients who had received kidneys from live, related donors (one identical twin) were able to maintain normal sodium balance. Peripheral plasma renin activity on a high-salt diet was 354 ± 28 mμg of angiotensin ∥ (±SE) in the donors and 291 ± 39 mμg per 100 ml in the recipients. Renin activity (low-salt diet) averaged 620 ± 50 mμg in the donors and 700 ± 52 mμg per 100 ml in the recipients. Aldosterone secretory rates were normal in the patients studied as were exchangeable sodium, potassium and body water. The denervated, transplanted human kidney can maintain clearance comparable with the donor kidney, and sodium regulation and renin secretion as evaluated in this study appear to be normal.

Vasopressin in the Evaluation of Pituitary-Adrenal Function

Abstract The plasma cortisol response to an intramuscular injection of 10 units of lysine vasopressin was evaluated in 19 normal subjects and in 35 patients with various disturbances of endocrine f...

The pattern of plasma renin activity and aldosterone secretion in normal and hypertensive subjects before and after saline infusions

Abstract The pattern of plasma renin activity and aldosterone secretion was studied in 56 unselected patients with essential hypertension and in 10 hypertensive patients with renal complications. The results were compared to responses found in 17 normal subjects and 6 patients with verified primary aldosteronism. In all cases, plasma renin activity and aldosterone secretion rates were measured under precise conditions of metabolic balance, initially during dietary salt restriction and then after physiologic saline infusions. Abnormally low responses in plasma renin activity to salt restriction were found in 13 patients with essential hypertension (25 percent), and in 4 there was no significant increase with standing. The expected increase in aldosterone secretion also failed to occur in 9 patients, 6 of whom demonstrated low plasma renin activity. The great majority of patients with essential hypertension responded normally to saline infusions with decreased plasma renin activity and aldosterone secretion, but in 4 patients the latter was greater than 300 μg/day after saline infusion. The response of hypertensive patients with renal complications was not different from that seen in uncomplicated cases. Although there was great variation in the responses seen in individual patients with essential hypertension, the combination of suppressed plasma renin activity and autonomous, excessive aldosterone secretion was found in only 1 patient. In this unselected series, the maximal incidence of primary aldosteronism (using the currently accepted criteria) was less than 5 percent.

Comparison of guanfacine versus clonidine for efficacy, safety and occurrence of withdrawal syndrome in step-2 treatment of mild to moderate essential hypertension

Guanfacine, an alpha 2-adrenoceptor agonist, was compared with clonidine as step-2 therapy of mild to moderate essential hypertension in a 24-week, double-blind, randomized, parallel evaluation to determine efficacy, safety and occurrence of withdrawal syndrome. During a 5-week period, patients were weaned from current antihypertensives, if any, and stabilized on step-1 therapy with 25 mg of chlorthalidone once a day. Those with a diastolic blood pressure (BP) from 95 to 114 mm Hg while taking chlorthalidone were randomized to treatment. The 2 agents had equal efficacy; 149 of 270 patients treated with guanfacine (55%) and 164 of 276 treated with clonidine (59%) achieved goal diastolic BP of less than or equal to 90 mm Hg. Terminations because of adverse effects were relatively low. Dry mouth (30% of guanfacine and 37% of clonidine groups) and somnolence (21% of guanfacine and 35% of clonidine groups, p less than 0.05) were reported most frequently. Nonsyncopal dizziness was reported in 11% of guanfacine-treated and 8% of clonidine-treated patients. This difference was not statistically significant. To evaluate the occurrence of a withdrawal syndrome in 316 outpatients and 156 inpatients, vital signs were monitored at least twice a day for up to 7 days after the end of therapy. Segmented 24-hour urine studies were performed on inpatients. Abrupt withdrawal of clonidine produced a rapid increase in diastolic and, especially, systolic BP, whereas guanfacine withdrawal produced more gradual increases. The differences were significant over the first 3 withdrawal days. It is concluded that guanfacine is a safe, effective, second-generation alpha 2-adrenoceptor agonist.(ABSTRACT TRUNCATED AT 250 WORDS)

The paradoxical dexamethasone response phenomenon

Abstract Two cases showing a paradoxical rise in urinary 17-hydroxycorticosteroids on 8 mg./day of dexamethasone as compared to their normal suppression on 2 mg./day of dexamethasone are reported. Attention is called to the existence of this phenomenon and several etiologic possibilities are discussed.

Effect of acute diuresis on aldosterone secretion in edematous patients.

Abstract In nine separate studies on four patients with severe pitting edema, aldosterone secretion fell during a 24-hour period of acute salt and water depletion induced by diuretics. These result...

The Role of the Adrenergic Nervous System in the Renal Response To Acute Extracellular Fluid Volume Expansion.

Summary The role of the adrenergic nervous system in the renal response to acute extracellular fluid (ECF) volume expansion was examined in the same dogs before and after catecholamine depletion with reserpine. In the control experiments before reserpine, acute ECF volume expansion produced marked increases in glomerular filtration rate (GFR). pamino-hippurate clearance (CPAH), mean arterial pressure (MAP), urine flow (V), sodium excretion (UNaV) and osmolar clearance (Cosm). One week later the same animals were studied under the same experimental conditions except for generalized impairment of the adrenergic nervous system secondary to catecholamine depletion with reserpine. The ECF volume expansion produced very similar increases in GFR, CPAH and filtered loads of sodium (FNa) before and after reserpine; however, the MAP, and thus renal perfusion pressures, were significantly lower after reserpine. Diminished urine flows (V), sodium excretion rates (UNaV) and osmolar clearances (Cosm) occurred after reserpine and correlated closely with the level of MAP. Since the FNa were comparable before and after reserpine, the effect of the lower MAP after reserpine on UNaV appeared to be related to a relatively greater tubular reabsorption of sodium. This study indicates, therefore, that the role of adrenergic nervous system in the renal pressure-flow relationships is an important factor in the natriuretic response to acute ECF volume expansion in dogs.

The pattern of electrolyte excretion in normal and hypertensive subjects before and after saline infusions. A simple electrolyte formula for the diagnosis of primary aldosteronism

Abstract Electrolyte excretion and serum electrolytes were studied in 99 subjects—19 normal subjects, 62 patients with essential hypertension, 10 with hypertension and renal disease, and 8 patients with primary aldosteronism—during administration of a low sodium diet and during 2 days of intravenous sodium loading. With saline infusions patients with primary aldosteronism gained significantly less weight, excreted significantly more potassium on each day of infusion, and excreted significantly more sodium on the first day of infusion only, than the other groups studied. Mean serum potassium levels fell significantly with saline infusions in patients with primary aldosteronism but remained unchanged in the other groups. From these observations a diagnostic formula based on potassium clearance corrected for sodium excretion was derived by which patients with primary aldosteronism could be separated completely from the other groups, with the exception of 1 patient with renal disease. Although patients with primary aldosteronism tended to have lower salivary sodium/potassium ratios than patients with essential hypertension, the difference was not significant.