Cardiopulmonary effects of volume expansion in man: radiographic manifestations.

Cardiovascular and humoral responses to extremes of sodium intake (10-1500 mEq/day) were studied. Chest radiographs of eight normal men were obtained to measure changes in heart volume and central vascular structures. Echocardiographic measurements of cardiac chamber dimensions were also obtained. Sodium loading resulted in a 16-mm-Hg increase in mean arterial pressure and increases in cardiac output, stroke volume, left ventricular end-diastolic volume, and all radiographically determined cardiac dimensions. There was direct correlation between the radiographic cardiac dimensions and left ventricular end-diastolic volume. There was no echocardiographic evidence of pericardial fluid. After sodium loading, there was enlargement of the superior vena cava, innominate veins, azygos vein, pulmonary vessels, and the aortic knob. Small pleural effusions were commonly seen. Volume expansion may cause radiographic changes that may mimic those associated with congestive heart failure. This may particularly be the case in patients with renal failure, those receiving dialysis treatment, or patients receiving large volumes of intravenous fluids.

Nephrotic syndrome and pregnancy. Potential problems for mother and child.

The pregnant patient with nephrotic syndrome should be carefully evaluated for the presence of chronic renal disease. Proteinuria itself may be associated with an increase in perinatal mortality and in the incidence of small-for-gestational-age infants. Coexistent hypertension and/or renal dysfunction add to the risk of an unsuccessful pregnancy. The use of tocolytic agents in pregnant women with nephrotic syndrome theoretically may be hazardous. The patient with systemic lupus erythematosus may be at particular risk of unsuccessful pregnancy if the disease is active; postponement of conception until a remission of six months or longer has been achieved may be well advised.

Enhancement of gentamicin nephrotoxicity by magnesium depletion in the rat.

This study examined the possible enhancement of gentamicin-induced nephrotoxicity by coexisting magnesium depletion. The effect of concurrent magnesium depletion on enhancing gentamicin-induced nephrotoxicity was measured by azotemia and mortality contrasted to magnesium repleted control rats also receiving gentamicin. After 28 days of dietary preparation, magnesium depleted rats and their magnesium repleted controls were each subdivided into 3 groups: (1) saline injection (NS); (2) gentamicin 80 mg/kg/day, and (3) gentamicin 120 mg/kg/day. Injections were continued for 14 days. All rats receiving gentamicin had proteinuria, increased mortality and significant renal morphological abnormalities. However, those rats which were concurrently magnesium depleted had statistically significant increments in BUN levels, more apparent renal tubular damage, and earlier mortality than the magnesium repleted controls. These observations support the view that concurrent magnesium deficiency in the rat enhanced gentamicin nephrotoxicity.

The effects of rapid saline infusion on sodium excretion, renal function, and blood pressure at different sodium intakes in man.

To examine the effects of increasing dietary sodium intake on natriuresis, filtration rate, and renal blood flow following rapid volume expansion, we infused 2-liter normal saline over 2 hr into normal men in balance at 10, 300, 600, and 800 mEq/day sodium intake. Natriuresis and kaliuresis were related to prior sodium intake. Fractional excretion of sodium (6%-7%) was maximal at the 600 mEq/day sodium intake and increased no further at the 800 mEq/day sodium intake. Although blood pressure increased with rapid saline infusion, natriuresis and blood pressure were not associated. Creatinine clearance decreased or remained constant, while PAH clearance decreased during saline infusion at each level. The data suggest that although natriuresis following rapid saline infusion is dependent upon prior sodium intake, under given circumstances it may be independent of glomerular filtration rate, renal blood flow, or blood pressure.

The blood pressure-raising effects of high dietary sodium intake: racial differences and the role of potassium.

Fourteen normotensive men (7 black, 7 white) were studied following equilibration during dietary sodium intake of 10, 300, 600, 800, 1200, and 1500 mEq sodium per day. Significant (p less than 0.05) increases in mean arterial blood pressure were seen after sodium intake of 800 mEq/d. Blood pressure increased at lower levels of sodium intake (800 mEq/d) and to a greater magnitude (21 mm Hg) in blacks than in whites (1200 mEq/d; 13 mm Hg). Sodium loading was associated with marked suppression of plasma renin activity, aldosterone and norepinephrine, and increases in cardiac index. At higher levels of sodium intake urinary potassium loss was seen. A subsequent experiment replacing urinary potassium losses as they occurred in six subjects demonstrated attenuation of the blood pressure increases seen in response to dietary sodium loading. These studies demonstrate a potential role for sodium and potassium in blood pressure regulation in normotensive man, and suggest that heterogeneity of response may be involved in the development of hypertension in individuals predisposed to avid sodium conservation.

Sodium intake alters the effects of norepinephrine on the renin system and the kidney.

To examine the interactions between sodium intake and the sympathetic nervous system and their influences on the blood pressure control system we studied eight normotensive men after high (800 mEq/d) and low (10 mEq/d) sodium intake. We measured blood pressure, arterial, venous and urinary norepinephrine (NE), glomerular filtration rate (GFR), renal blood flow (RBF), plasma renin activity (PRA) and aldosterone (PA), and the fractional excretion of sodium (FENa) and potassium (FEK) before and during incremental infusion of norepinephrine. High salt intake influenced the sensitivity to NE as well as subsequent pressor responses. The NE-induced decrease in RBF and GFR was not different on high and low sodium intakes. A significant decrease in FENa (p less than 0.05) with NE infusion could only be seen during high sodium intake. A significant increase in PRA (p less than 0.01) and PA (p less than 0.05) was induced by NE only during the low sodium period. These observations reveal previously unrecognized qualitative and quantitative interactions between sodium homeostasis and norepinephrine which are capable of influencing blood pressure in man.

Sodium intake alters the effects of norepinephrine on blood pressure.

To examine the interactions between sodium balance and the sympathetic nervous system, we studied eight normotensive men after high (800 mEq/day) and low (10 mEq/day) sodium intake. We measured blood pressure (BP), arterial, venous, and urinary norepinephrine (NE) before and during incremental infusion of NE. We found significant direct, linear relationships (p less than 0.001) between the dose of NE infused and arterial and venous NE levels, and with mean arterial BP at both levels of sodium balance. In addition. the sensitivity was greater and the threshold of pressor response to NE as well as the basal concentrations of NE in arterial and venous plasma significantly lower (p less than 0.05) after the high sodium period. These observations expose heretofore unrecognized qualitative and quantitative interactions between sodium balance and NE that are capable of influencing BP in man.

Urinary calcium excretion at extremes of sodium intake in normal man.

To elucidate the relationship between the renal regulation of sodium and calcium excretion at extremes of sodium intake, we studied 6 normal men ingesting a fixed, 400 mg/day calcium intake and four levels of sodium intake from 10 to 1,500 mEq/day. Serum ionized calcium was not influenced by sodium intake. Blood pressure and cardiac index increased modestly. Urinary calcium excretion increased to 262 +/- 53 mg/day (mean +/- SE). Plasma norepinephrine concentration, serum PTH levels, hematocrit, total serum protein concentrations and CO2 content decreased with increasing sodium intake. Urinary cAMP increased as sodium intake was raised from 10 to 300 mEq/day, but subsequently decreased to basal values. Urinary calcium and sodium excretion were related (p less than 0.001) in a nonlinear fashion as were the fractional excretions of these cations (p less than 0.001). The filtered calcium load and the fractional calcium excretion were directly and linearly related (p less than 0.001). We conclude that the effect of sodium intake on urinary calcium excretion principally reflects changes in the filtered calcium load rather than changes in renal sodium handling. Calcium homeostasis at extremes of sodium intake does not appear to be critically dependent upon PTH-mediated mechanisms. The data suggest that the proximal tubule has a remarkable capacity to dissociate calcium resorption from that of sodium.

Blood pressure of alloxan diabetic rats at regular and high salt intake.

To identify any relationship between diabetes mellitus and high salt intake in the production of hypertension, we studied the effect of a regular and high salt diet on blood pressure in rats made diabetic with alloxan. The diabetic animals developed marked hyperglycemia, glycosuria, and azotemia out of proportion to changes in glomerular filtration rate. Non-diabetic rats and diabetic rats on a high salt intake in excess of 14 mEq/day developed modest but significant increases in blood pressure, while diabetic rats on a regular diet did not. We conclude that diabetic rats have no greater susceptibility to salt-induced hypertension than rats receiving only salt. Although it is possible that dehydration may have served to attenuate blood pressure increases in our diabetic animals, the diabetic state per se does not appear to result in severe hypertension in the rat regardless of sodium intake.