Hypotensive and diuretic effects of atrial natriuretic factor in diabetic patients.

Plasma levels of atrial natriuretic factor (ANF), and the effects of intravenously infused ANF (99-126) on renal filtration and blood pressure, were studied during different sodium intakes in six patients with uncomplicated diabetes mellitus. The change from a low (25 mmol/day) to a high (241 mmol/day) sodium intake was associated with a 2.5 fold increase in circulating immunoreactive ANF. On both sodium diets, an infusion of synthetic ANF (99-126) given at two different rates caused a progressive decrease of arterial pressure. On a low but not on a high sodium intake arterial hypotension occurred in two patients. Moreover, on a high sodium intake, ANF did not significantly modify glomerular filtration rate, the effective renal plasma flow and the plasma concentrations of renin and aldosterone. It increased the fractional excretion of sodium by 72%. On a low sodium intake ANF caused a progressive fall of glomerular filtration rates and effective renal plasma flow. It increased the fractional excretion of sodium by 100%, and increased plasma renin and aldosterone levels. In patients with uncomplicated diabetes mellitus, circulating ANF responds physiologically to variations in sodium intake. A low sodium diet could predispose to arterial hypotension and renal functional impairment during infusion of ANF (99-126).

Stimulation of renin secretion by potassium-channel activation with cromakalim.

The cardiovascular and endocrine profile of cromakalim has been studied in 8 healthy men (age 25 +/- 2 years: means SEM) and its influence on renin release from cultured rat juxtaglomerular cells in vitro has also been examined. According to a double-blind, randomized sequence the subjects received placebo or cromakalim 1 mg as a single daily oral dose for 5 days. Compared to placebo, cromakalim significantly increased plasma renin activity (+ 122%; from 1.73 to 3.87 ng AI.ml-1.h-1), angiotensin II (+ 105%; from 5.1 to 10.5 pg.ml-1), and norepinephrine (+ 61%) levels, and heart rate (+ 8%). Plasma aldosterone, blood pressure and indices of the electrolyte-fluid volume state were unchanged. Cromakalim in vitro stimulated renin release, from 9.9 to 36.5 ng AI.h-1.30 min.mg cell protein, from juxtaglomerular cells. It appears that the presumed K+-channel activator cromakalim increases renin release in vivo at least in part by direct stimulation of renal juxtaglomerular cells.

Sodium and responses to infused noradrenaline and angiotensin II in subjects predisposed to hypertension.

A disturbed adrenergic dependent blood pressure regulation may represent a familial component in the pathogenesis of essential hypertension; its possible relation to sodium metabolism is presently unknown. Body sodium, the cardiovascular pressor reactivity to infused noradrenaline or angiotensin II, plasma levels of noradrenaline, adrenalin, renin, angiotensin II, aldosterone and atrial natriuretic peptide were measured on a low or high sodium diet in 10 normotensive young subjects without and 13 normotensive subjects with familial predisposition to hypertension. On the low sodium diet, the two groups did not differ significantly in the considered parameters, while blood pressure was slightly higher in predisposed subjects (+7/+7 mmHg). The change from the low to the high sodium diet was associated with a significant increase in supine systolic blood pressure in predisposed but not in non-predisposed subjects (P less than 0.05). Exchangeable sodium, body weight atrial natriuretic peptide and the pressor reactivity to infused adrenalin or angiotensin II increased significantly while plasma catecholamines, renin, angiotensin II and aldosterone levels were suppressed to a comparable extent in the two groups. The findings of this investigation confirm that sodium has an important regulatory effect on cardiovascular pressor responsiveness. The disturbed noradrenergic-dependent regulation of predisposed subjects is not explained by an abnormal adaptation of sympathetic dependent mechanisms or of other pressor factors to variations in dietary sodium intake.

Blunted aldosterone responsiveness to angiotensin II in normotensive subjects with familial predisposition to essential hypertension.

The responsiveness of plasma aldosterone to an angiotensin (Ang) II infusion was assessed in normotensive young men, nine without and 13 with a family history of essential hypertension, after 7 days of low (mean urinary sodium 12 +/- 10 mmol/24 h) and 7 days of high (269 +/- 92 mmol/day) sodium intake. Under both conditions, the two study groups did not differ in body weight, arterial pressure, heart rate, plasma or urinary sodium and potassium or plasma renin, aldosterone or Ang II levels. However, after both dietary periods, the relationship between plasma aldosterone and plasma Ang II concentrations had shifted significantly (P less than 0.01) to the right in predisposed compared to non-predisposed subjects. The sodium-related changes in adrenocortical sensitivity to Ang II were similar in the two groups. The pressor response to Ang II did not differ between the two groups of subjects. These findings suggest that, in addition to the known cardiovascular abnormalities of sympathetic, renal and ion transport mechanisms, a fourth area of disturbance involving the response of plasma aldosterone to Ang II may be present in normotensive subjects with familial predisposition to essential hypertension.

Renal tubular handling of sodium and familial predisposition to essential hypertension.

Renal clearance of lithium and sodium, glomerular filtration rate, renal plasma flow and certain other parameters of proximal tubular function were determined in 10 normotensive men without, and 13 normotensive men with a family history of essential hypertension after a low- and high-sodium diet. Under low-sodium conditions, the two groups did not differ in mean body weight, exchangeable sodium, plasma renin activity, clearances of inulin, para-aminohippurate (PAH), lithium, sodium, potassium, uric acid or inorganic phosphate, although blood pressure tended to be slightly, but not significantly, higher in those with a family history of hypertension. After changing to the high sodium diet, body weight, exchangeable sodium, and sodium clearance increased and renin decreased significantly (P less than 0.05) and to a similar extent in the two groups; systolic blood pressure increased only in subjects with a family history of hypertension. In both groups renal clearances of inulin, PAH, lithium, potassium, uric acid and inorganic phosphate remained unchanged. These findings do not support the concept that familial predisposition to hypertension is associated with an enhanced proximal reabsorption of sodium. Moreover, the pressor response to a high sodium intake in predisposed subjects is not mediated by an abnormal adaptation of renal sodium metabolism.

[Acute treatment of arterial hypertension using calcium antagonists: comparison between diltiazem and nifedipine]. / Akute Behandlung der arteriellen Hypertonie mit Calcium-antagonisten: Diltiazem im Vergleich zu Nifedipin.

Calcium antagonists have been used for the acute treatment of hypertension. Among these compounds, diltiazem induces the least tachycardia in response to acute administration. The effects of this agent, in a dose of 0.3 mg/kg given intravenously, on arterial pressure, heart rate and plasma renin activity were assessed in 10 patients with benign moderate to severe essential hypertension; nifedipine (10 mg sublingually) in 10 patients or 5% glucose (placebo) in 4 patients was used as a control. As compared with the 5% glucose group, diltiazem caused a persistent fall in diastolic pressure during 60 minutes, but only a transient decrease in systolic arterial pressure and heart rate; plasma renin activity was unchanged. Nifedipine caused a persistent fall in both systolic and diastolic pressure and a slight but significant increase in plasma renin activity, but did not modify heart rate. The diltiazem-induced decrease in systolic pressure was significantly smaller than the pressure changes caused by nifedipine. Variations in plasma renin activity between the two calcium antagonists were not significant. These findings suggest that in patients with hypertension diltiazem exerts a less marked acute antihypertensive effect than nifedipine.

Blood pressure regulation on low and high sodium diets in normotensive members of normotensive or hypertensive families.

In members of hypertensive families a high sodium intake may have a pressor effect. The mechanism mediating the sodium sensitivity is unclear. Blood pressure, exchangeable sodium, plasma levels of norepinephrine, epinephrine, renin and aldosterone, the pressor response to infused norepinephrine or angiotensin II and the urinary excretion of prostaglandin (PG) E2 and F2 alpha were measured after 7 days of low sodium diet (urinary sodium 13 +/- 10 s.d. mmol/24 h) and 7 days of high sodium intake (urinary sodium 268 +/- 97 mmol/24 h) in 10 normotensive men without and 13 men with family history of essential hypertension. After the low sodium phase, blood pressure, heart rate, exchangeable sodium, plasma levels of norepinephrine, epinephrine, renin and aldosterone, pressor doses of norepinephrine or angiotensin II and the urinary excretion of PGE2 or PGF2 alpha did not differ between the two groups. After the high sodium phase, blood pressure increased only in subjects with positive (P less than 0.05) but not in those with negative family history. In the two groups exchangeable sodium increased (P less than 0.05) and plasma levels of NE (-33% versus -32%), renin (-31% versus -27%) or aldosterone (-74% versus -61%) and pressor doses of NE (-55% versus -54%) or ANG II (-72% versus -44%) decreased by a comparable extent. Urinary PGE2 or PGF2 alpha were unchanged. These findings suggest that a high dietary sodium intake exerts a pressor effect in subjects with familial predisposition to essential hypertension. This pressor effect is not explained by an abnormal adaptation of body sodium, sympathetic activity, renin-angiotensin-aldosterone axis, cardiovascular pressor responsiveness and renal prostaglandin excretion to a high sodium diet.

Phase I trial of 4'-deoxydoxorubicin given weekly.

Twenty-six patients with various solid tumors entered a Phase I trial with 4'-Deoxydoxorubicin (Esorubicin, IMI-58), a new doxorubicin analogue. The drug was administered weekly i.v. for 3-4 weeks. Leukopenia proved to be dose limiting. The maximum tolerated dose (MTD) was reached at 20 mg/m2 weekly for 3 weeks. For Phase II trials, a weekly dose of 15 and 17.5 mg/m2 can be proposed for poor and good risk patients respectively. Non-hematologic toxicity was minimal. Phase II trials with this new anthracycline are warranted.

Gallstone ileus after endoscopic sphincterotomy.

An attack of gallstone ileus observed in a 60-year-old female patient is reported. In this patient who previously had been cholecystectomized, instant extraction of giant residual gallstones was unsuccessful despite a large endoscopic sphincterotomy. Three days later, she developed colicky abdominal pain and vomiting. At laparotomy nine days after the endoscopic procedure an impacted gallstone measuring 3.5 cm in diameter was removed from the the jejunum, some 50 cm below the ligament of Treitz. This observation demonstrates an unusual complication of endoscopic sphincterotomy and clearly outlines that very large stones can, after an initial delay, pass into the duodenum despite an apparently "unsuccessful" sphincterotomy.

Influence of early mobilisation of pulmonary function in surgical patients.

This work confirms the generally known decrease in arterial oxygen following surgery. On the basis of a more rapid restitution of pulmonary function the superiority of mobilization to the usual respiratory exercises is clearly shown.