Alfred Casper

INCREASED ALDOSTERONE SECRETION IN DOGS WITH RIGHT- SIDED CONGESTIVE HEART FAILURE AND IN DOGS WITH THORACIC INFERIOR VENA CAVA CONSTRICTION

Studies (1-5) of patients with congestive heart failure, decompensated hepatic cirrhosis and nephrosis have provided evidence of increased amounts of aldosterone or aldosterone-like substances in urine during edema or ascites formation. More recently, it has been demonstrated (6) that increased urinary excretion of aldosterone occurs in association with sodium retention in dogs with right heart failure and in dogs with ascites secondary to constriction of the thoracic inferior vena cava. The data in both man and dog imply that the blood level of aldosterone is elevated. Numerous attempts have been made to elucidate the mechanism regulating aldosterone secretion in clinical states associated with the formation of edema, but no data have been reported to show that increased circulating aldosterone results from increased secretion rather than from a decreased rate of inactivation. The purpose of this study was to determine the relative rates of secretion of aldosterone in 1) dogs with cardiac failure produced by stenosis of the pulmonary artery, 2) dogs with thoracic inferior vena cava constriction and ascites, and 3) normal dogs.

Depression of proximal tubular sodium reabsorption in the dog in response to renal beta adrenergic stimulation by isoproterenol

Water diuresis was produced in anesthetized hypophysectomized, cortisone-treated dogs by infusion of 2.5% dextrose. Alpha adrenergic blockade of the left kidney produced by infusion of phenoxybenzamine in the left renal artery was associated with a significantly (P < 0.05) greater rate of urine flow (V) and free water excretion (C(H2O)) in the left kidney than in the right despite similar glomerular filtration rates (GFR) (17 +/- 1.3 ml/min, left; 18 +/-0.9 ml/min, right). Sodium excretion (U(Na)V) was similar in the two kidneys (3 and 5 muEq/min). When beta adrenergic stimulation of the left kidney was superimposed on alpha blockade by the addition of isoproterenol to the left renal artery infusate, GFR remained unchanged and similar in the two kidneys, as V and C(H2O) increased significantly (P < 0.01) in the left kidney but not in the right. When isoproterenol was discontinued, V and C(H2O) returned towards control in the left kidney and remained unchanged in the right. The ratios of the left kidney to the right during control, isoproterenol, and postcontrol were 1.22, 1.65, and 1.35, respectively, for V and 1.36, 1.90, and 1.44, respectively, for C(H2O). Sodium excretion remained unchanged and similar in the two kidneys throughout the study. The results indicate that blockade of alpha adrenergic activity inhibits the increased proximal tubular sodium reabsorption which anesthesia induces in the dog. Beta adrenergic stimulation appears to decrease proximal tubular sodium reabsorption but does not prevent virtually complete reabsorption of the increased quantity of delivered sodium by the ascending limb of the loop of Henle and the distal tubule. These changes in sodium reabsorption presumably are not associated with changes in colloid osmotic pressure or hydrostatic pressure in the peritubular capillary inasmuch as cortical and non-cortical plasma flow, filtration fraction, and mean arterial pressure in the left kidney were unchanged. Thus, isoproterenol probably produced its effects through a direct action on the renal tubule, possibly through the mediation of the adenyl cyclase system.

Right-Sided Congestive Heart Failure in Dogs Produced by Controlled Progressive Constriction of the Pulmonary Artery

Right heart failure was produced in dogs by controlled progressive stenosis of the pulmonary artery. Cardiac enlargement, systemic venous engorgement, tachycardia, hepatomegaly and ascites were consistent findings. The course of cardiac failure was characterized by continual changes in cardiovascular hemodynamics; either cardiac decompensation became progressively severe or circulatory function improved and diuresis resulted. Sodium (Na) retention was always associated with high central venous pressure. Cardiac output was reduced during Na retention except during spontaneous anemia superimposed on cardiac failure. Glomerular filtration rate was frequently normal at the onset of cardiac failure.

On the role of the vagus in the control of aldosterone secretion.

Aldosterone in adrenal venous blood of dogs is increased by constriction and decreased by release of constriction of the inferior vena cava. Section of the cervical vagi did not affect the rise of aldosterone but prevented its fall. The receptors for stimuli to increases of aldosterone secretion may not be the same as those for stimuli to decreases.

Role of the sympathetic nervous system in the renal response to hemorrhage

In 12 studies, a femoral artery and vein of a donor dog treated with desoxycorticosterone were connected by tubing to a renal artery and vein of a recipient dog treated with desoxycorticosterone, and the kidney with its nerve supply intact was perfused at femoral arterial pressure. Infusion of normal saline, which contained albumin, from 2.7 to 3.1 g/100 ml, in the donor produced significant natriuresis in a kidney of the donor (from 112 to 532 muEq/min) and in the perfused kidney (from 60 to 301 muEq/min) of the recipient. Increased sodium excretion in the perfused kidney was associated with an increase in the clearances of inulin and para-aminohippurate (P < 0.01) and a decrease in hematocrit of perfusing blood (P < 0.01). Infusion was continued in the donor while recipient was bled 23 ml/kg, with a decrease in mean arterial pressure from 152 to 130 mm Hg. Sodium excretion in perfused kidney decreased from 301 to 142 muEq/min (P < 0.01), whereas sodium excretion in donor was unchanged (506 VS. 532 muEq/min; P > 0.3). Clearance of inulin by perfused kidney was not significantly affected by bleeding (26 +/-SE 2 VS. 25 +/-SE 2; P > 0.2), but the clearance of para-aminohippurate was decreased by bleeding (P < 0.01), so that filtration fraction increased. As the perfused kidney of the recipient dog continued to receive blood from the natriuretic donor dog when the recipient dog was bled, the decrease in sodium excretion that bleeding produced in the perfused kidney was presumably mediated by renal nerves. Thus, an increase in nervous stimuli to the kidney that is not sufficient to decrease glomerular filtration rate can increase the tubular reabsorption of sodium and thereby significantly decrease its excretion. This property of the sympathetic nervous system to affect tubular reabsorption of sodium suggests that an increase in sympathetic activity may constitute an important mechanism for the renal conservation of sodium when intravascular volume is contracted by hemorrhage or other cause.

Studies of Actomyosin from Cardiac Muscle of Dogs with Experimental Congestive Heart Failure

Comparative studies were made on cardiac actomyosin from normal dogs and from dogs with experimental failure. Actomyosin was characterized by ultracentrifugal sedimentation velocity, viscosity and ATP-ase measurements. The data on actomyosin from normal cardiac muscle showed a striking similarity to the findings reported by others for skeletal muscle actomyosin. The only difference found between cardiac actomyosin front the normal and experimental material was an abnormal component (S20W = 5.0–6.7) in the sedimentation pattern for actomyosin from 4 of 11 dogs with cardiac failure. It seems likely that the changes in actomyosin which resulted in the abnormal sedimentation pattern were produced during extraction or preparation of the actomyosin and that they do not reflect an altered state of actomyosin in the functioning heart. The explanation for the occurrence of this slow sedimentation component solely in the experimental material is not clear.

Physiologic Changes during Chronic Congestive Heart Failure in Dogs with Tricuspid Insufficiency and Pulmonic Stenosis

chronic congestive heart failure was studied in dogs with surgically-produced tricuspid insufficiency and pulmonic stenosis. Ascites formed in association with an elevation in mean right atrial pressure. The volume of ascitic fluid and the rate of urinary sodium excretion varied greatly in individual dogs during the course of congestive failure and among the different animals. Sodium retention was most common but periods of sodium balance and natriuresis occurred. Comparative data on the right and left ventricles were obtained from determinations of intracardiac pressures, measurements of ventricular muscle mass at the time of sacrifice and studies of the lungs for evidence of chronic passive congestion. There was significant right ventricular hypertrophy but no evidence of left ventricular hypertrophy or failure.

Functional Changes During High Output Failure Produced by Daily Hemorrhage in Dogs with Pulnionic Stenosis

The relationship of changes in cardiovascular and renal hemodynamic function to sodium excretion has been studied following daily hemorrhage in dogs with pulmonic stenosis and in normal dogs. The animals with pulmonic stenosis developed signs of right heart failure, but the normal dogs failed to show evidence of cardiac decompensation during the course of the anemia. The two most striking differences in the responses of the 2 groups of dogs were the increase in mean right atrial pressure and the occurrence of sodium retention, both of which were observed only in the dogs with pulmonic stenosis. The increase in cardiac output and the renal functional changes were similar in the 2 groups of animals; glomerular filtration rate was unchanged or increased in the majority of dogs with pulmonic stenosis and heart failure.

Effect of Hypophysectomy on Electrolyte Excretion in Dogs with Ascites Produced by Thoracic Inferior Vena Cava Constriction

Following complete or nearly complete hypophysectomy in dogs with thoracic inferior vena cava constriction, a striking increase in sodium (Na) excretion occurred concomitant with a fall in femoral venous pressure. The previously high venous pressure and renal Na retention were restored by administration of thyrotropin (TSH), growth hormone injection or further constriction of the thoracic inferior vena cava, but adrenocorticotropic hormone (ACTH) was without effect on these functions. The data indicate that pituitary hormones influence the accumulation of ascitic fluid by contributing to the maintenance of an adequate level of venous hypertension.

On the role of the central nervous system in control of aldosterone secretion

Abstract Neither pineal extracts nor 1-methyl, 6-methoxy tetrahydro carboline stimulated adrenal steroid secretion in the dog. In hypophysectomized, nephrectomized dogs, secretion rates for aldosterone, corticosterone and cortisol fell to very low levels. When hypophysectomized, nephrectomized dogs were subjected to mid-collicular brain section with removal of forebrain, secretion rates for aldosterone, corticosterone and cortisol were significantly higher than those found after hypophysectomy and nephrectomy alone. Aldosterone secretion rose to rates comparable to those found after hemorrhage, caval constriction or salt depletion in intact or hypophysectomized dogs.