Caval Constriction Research Articles

Effects of Renal Arterial Infusion of Sodium and Potassium on Renin Secretion in the Dog

The nonfiltering kidney model was used to determine whether sodium or potassium inhibits renin secretion in the absence of a functional macula densa in dogs with thoracic inferior vena caval constriction. The control rate of renin secretion was high, and decreases were readily recognized. After control observations, hypertonic sodium chloride or hypertonic potassium chloride was infused into the renal artery for 1 hour, and renin secretion was measured at 15-minute intervals. An increase in renal venous plasma sodium concentration from 141 to 154-158 mEq/liter caused no change in renin secretion for the first 45 minutes of infusion in dogs with a nonfiltering kidney. In contrast, dogs with thoracic caval constriction but with a filtering kidney showed a striking decrease in renin secretion during intrarenal sodium infusion (3,097 to 1,061 ng angiotensin/min, P <0.02). An increase in renal venous plasma potassium concentration from 3.9 to 6.1 mEq/liter in one group of dogs and from 4.9 to 8.3 mEq/liter in a second group also caused no change in renin secretion in the nonfiltering kidney of dogs with thoracic caval constriction. However, in dogs with thoracic caval constriction and a filtering kidney, potassium infusion decreased renin secretion (1,952 to 984 ng angiotensin/min, P <0.05). In all experiments, infusion of sodium chloride or potassium chloride failed to produce a significant change in renal blood flow, arterial blood pressure, or inferior vena caval pressure. Therefore, no evidence was obtained for a vascular action or a direct effect of sodium or potassium on the juxtaglomerular cells, and the data are consistent with an action mediated by the renal tubular system.

Mechanisms regulating renin release in dogs with thoracic caval constriction.

In dogs with chronic thoracic caval constriction, renal denervation was followed by a fall in plasma renin activity from an average of 82.1 ± 1.5 (SE) ng angiotensin/ml of plasma over a 9-day control period to 40.8 ± 2.3 ng/ml for a 13-day period after denervation ( P < 0.001); normal value was 4.7 ± 0.7 ng/ml. There was no detectable effect of renal denervation on the marked sodium retention. Thus the renal nerves contributed to the high plasma renin activity during caval constriction, but renal innervation was not essential for hypersecretion of renin. In a second group of dogs with caval constriction, the nonfiltering kidney model with a nonfunctional macula densa was produced, and renin secretion was measured before and after papaverine infusion into the left renal artery. Papaverine decreased renin secretion from 1090 ± 185 ng angiotensin/min to 497 ± 140 ng/min ( P < 0.005). This initial rate of renin secretion of 1090 ng/min was higher than that from a nonfiltering left kidney of 190 ± 50 ng/min in otherwise normal dogs ( P < 0.001). In a third series of dogs with caval constriction but with filtering kidneys, papaverine produced a similar decrease in renin secretion and an associated increase in sodium excretion. Since papaverine dilated the renal arterioles and the macula densa was nonfunctional in dogs with a nonfiltering kidney, these data support the concept that an intrarenal vascular receptor mediates the elevation in renin secretion in this model with chronic ascites. The striking decrease in renin secretion in response to intrarenal propranolol in dogs with either a filtering or a nonfiltering kidney indicates that a beta receptor is also involved.

Failure to demonstrate a humoral mechanism in the antinatriuresis of acute caval constriction.

Previous studies reported from this laboratory provided support for the hypothesis that the natriuresis of volume expansion is mediated in part by a humoral mechanism. In the present study we examined whether suppression of this factor participates in the antinatriuresis of acute constriction of the thoracic inferior vena cava. An isolated kidney was perfused by a second dog pretreated with deoxycorticosterone acetate. Expansion of the perfusion dog with equilibrated blood from a reservoir resulted in an increase in sodium excretion from 102+/-30 to 259+/-65 muEq/min, P < 0.001. Fractional sodium excretion increased from 2.3+/-0.6 to 6.2+/-1.2%, P < 0.01. Inulin clearance, plasma protein concentration, and packed cell volume remained constant; renal perfusion pressure and renal blood flow decreased. After the natriuresis was established, the thoracic inferior vena cava was constricted to decrease systemic arterial pressure in the perfusion dog 50 mm Hg. This maneuver suppressed urine output in the dog but did not significantly alter sodium excretion in the isolated kidney. During the period of caval constriction absolute sodium excretion in the isolated kidney measured 198+/-42 muEq/min and fractional sodium excretion measured 5.7+/-1.1%. Neither value is significantly different from that measured during volume expansion alone. The data suggest that the antinatriuresis of acute caval constriction probably does not require suppression of a humoral natriuretic factor and that other more rapidly acting mechanisms, presumably hemodynamic and neural, may be involved.

Proximal tubular function in dogs with thoracic caval constriction.

The effect of saline infusion on proximal sodium reabsorption was compared in normal dogs and in dogs with acute or chronic partial thoracic vena cava obstruction. After acute vena cava obstruction, proximal fractional sodium reabsorption rose by 74%. During continued caval obstruction, saline loading strikingly reduced proximal reabsorption but sodium excretion remained minimal. In chronic caval dogs, saline loading reduced proximal fractional sodium reabsorption by 31% but sodium excretion in the micropunctured kidney was only 41 muEq/min. After saline infusion in normal dogs, proximal fractional sodium reabsorption fell 39% while unilateral sodium excretion rose to 584 muEq/min. Nephron filtration rate was also measured before and after saline loading in normal and chronic caval dogs in both repunctured and fresh tubules. There was a marked increase in nephron filtration rate in repunctured tubules and no change in freshly punctured tubules in both groups. The effect of saline loading on nephron filtration rate in normal and chronic caval dogs was similar, therefore, whether repunctured or fresh nephrons were considered.We conclude that saline infusion depresses proximal sodium reabsorption in acute and chronic TVC dogs. Since saline loading markedly increases distal delivery without a concomitant natriuresis, enhanced distal reabsorption must play a major role in the sodium retention exhibited by chronic caval dogs. Redistribution of filtrate does not appear to be a factor in this sodium retention.

Escape from sodium-retaining effects of deoxycorticosterone in hypotensive and hypertensive dogs.

SummaryThe ability of the mammalian kidney to escape from the sodium-retaining effects of mineralocorticoid hormones has not been thought to depend upon increases in blood pressure or renal perfusion. However, chronic exposure to excess endogenous or exogenous adrenal cortical hormones results in hypertension, and it seemed possible that early small increments in blood pressure might play a role in escape. To evaluate this, hypotension was produced with drugs in dogs, and their ability to escape was studied. A combination of hydralazine and guanethidine effectively lowered blood pressure but did not prevent or delay renal escape from deoxycorticosterone. Production of hypotension after escape resulted in sodium retention for 1 day, but then sodium balance resumed despite continued hypotension and lowered renal blood flow and filtration. Mean arterial blood pressure in dogs with thoracic inferior vena caval constriction was not significantly below normal, and elevation of blood pressure with ephedrine fail...

A further study of adrenal function in the opossum (Didelphis virginiana).

Abstract Studies are reported on the in vitro metabolism of progesterone-4- 14 C by adrenal tissue taken from the American opossum ( Didelphis virginiana ) before and after chronic caval constriction. Comparison of paired adrenals from the same animal showed that this procedure diverted steroid metabolic pathways to produce more mineralocorticoid and less glucocorticoid but aldosterone levels were reduced in favor of deoxycorticosterone. Thoracic caval obstruction sufficient to produce a fall in mean arterial pressure caused a marked rise in aldosterone secretion in as short a period of time as 15 min, in some cases. A single injection of 1–2 μg of aldosterone caused a marked decline in urinary sodium excretion which did not appear until the second hour after administration of the steroid. The effect on potassium was variable. In these three respects the adrenal steroid metabolism and utilization in the American opossum appear to be similar to that of higher mammals.

Effect of expansion of extracellular fluid volume on renal phosphate handling.

To examine the specific effect of extracellular fluid (ECF) volume expansion on phosphate excretion studies were performed in thyroparathyroidectomized dogs receiving saline solution intravenously. The natriuresis resulting from ECF volume expansion was consistently accompanied by an increase in phosphate excretion. The possible role of increased filtered load of phosphate was eliminated in experiments in which the filtered load of phosphate was reduced by acute reduction in the glomerular filtration rate. Despite considerable reductions in filtered phosphate, ECF volume expansion resulted in a consistent increase in phosphate excretion. Furthermore, the possible contribution of alteration in blood composition was investigated in experiments in which saline was infused during thoracic inferior vena cava constriction. In these experiments saline infusion failed to increase sodium or phosphate excretion. Cessation of saline infusion and release of caval constriction resulted in a prompt natriuresis and increased phosphate excretion. It is concluded from these studies that extracellular fluid volume expansion results in an increased phosphate excretion in the parathyroidectomized dog. This effect is the specific consequence of ECF volume expansion and is not due to increase in the filtered load of phosphate or alterations in blood composition.

Steroidogenic response in normal dogs receiving blood from dogs with caval constriction.

Steroidogenic response in normal dogs receiving blood from dogs with caval constriction.

Experimental studies of factors influencing hepatic metastases. 18. Significance of trapped tumor cells.

SummaryNo increase in numbers of intra-portally injected 51Cr-labeled Walker tumor cells was detected in livers of rats subjected to partial hepatectomy, hepatic manipulation, reticuloendothelial blockade, high fat, choline-free diet, caval constriction, or injection of dextran. This information indicates that the augmentation of hepatic metastases produced by these modalities in this model system is related to their metabolic or biologic (“soil”) rather than mechanical influences on hepatic-tumor cell relationships.

Relation of plasma renin to sodium balance and arterial pressure in experimental renal hypertension.

Measurements of plasma renin were made in unilaterally nephrectomized dogs with renal artery stenosis and hypertension. Plasma renin was elevated throughout the course of the malignant renal hypertensive disease, and during the first three days only in chronic hypertension. Hypertension was produced by renal artery constriction in unilaterally nephrectomized dogs with prior thoracic caval constriction and in sodium-depleted, left nephrectomized animals. Plasma renin was high in both dogs with caval constriction and sodium depletion before hypertension was added. When the renal artery was constricted, two of the dogs with thoracic caval constriction developed malignant hypertension and a further striking increase in plasma renin occurred. In two other dogs with caval constriction, chronic hypertension developed but plasma renin increased further in only one of the two animals; this occurred during the first four days of hypertension after which plasma renin returned to the high control level. The sodium-depleted dogs developed chronic hypertension following renal artery constriction but no further elevation in plasma renin occurred. Sodium repletion and sodium depletion of chronic hypertensive dogs produced marked changes in plasma renin without alterations in arterial pressure. The present findings revealed a striking correlation between plasma renin and sodium balance but neither bore any relation to the level of arterial pressure.

The effect of suprahepatic caval constriction on the renal response to acidosis.

When unanæsthetized caval constricted rats which were retaining sodium were subjected to metabolic acidosis, they showed a significantly lower rate of hydrion excretion and a greater fall in plasma pH and bicarbonate than normal rats.Glomerular filtration rate was not significantly reduced by caval constriction but filtration fraction was increased.An aldosterone‐blocking steroid and an osmotic diuretic were both effective in increasing hydrion excretion in caval constricted rats, but had no significant effect in normal rats.It is suggested that the low rate of hydrion excretion was caused by the failure of sodium to reach the distal parts of the tubular ion exchange mechanisms in adequate amounts.

Hematochyli in Man and Animals

Dumont and Mulholland 1 2 in 1962 were the first to describe gross contamination of the thoracic-duct lymph with blood in man. They made the observation in 20 patients with Laennec's cirrhosis and postulated that this phenomenon resulted from an increased hepatic sinusoidal pressure. In this condition, red blood cells are presumed to lead from the sinusoids into the hepatic lymphatics. However, this conclusion is not substantiated by a considerable number of experimental studies in which inferior vena caval or hepatic venous constriction has been used in the production of ascites in dogs. 3-5 Such animals exhibit a similar increase in thoracic-duct flow rate to that described by Dumont and Mulholland in man, but no instance of hematochyli has been described. We became interested in this area when animals with chronic abdominal arteriovenous fistulas, being studied for unrelated purposes, were found to have bloody chyle. An experimental study, therefore, was

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

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.

SODIUM EXCRETION DURING ACUTE SALINE LOADING IN DOGS WITH VENA CAVAL CONSTRICTION.

SODIUM EXCRETION DURING ACUTE SALINE LOADING IN DOGS WITH VENA CAVAL CONSTRICTION.

Mechanisms of hemodynamic control of secretion of aldosterone in the dog

Changes in aldosterone and cortisol secretions were measured in response to constriction of the thoracic inferior vena cava and of the carotid arteries in intact and nephrectomized dogs. Aldosterone and cortisol secretions increased and decreased normally in response to caval constriction and release in nephrectomized animals. Carotid constriction in intact animals increased aldosterone secretion to the same extent as caval constriction, but without increasing cortisol secretion. Cortisol secretion rose after carotid constriction in vagotomized dogs. Nephrectomy led to transient low rates of aldosterone secretion in otherwise intact animals and prevented the increase of aldosterone secretion following carotid constriction in most, but not all, animals in which there was no evidence for ACTH release. Since carotid constriction decreases renin secretion, this effect of nephrectomy is probably independent of the renin-angiotensin system. The data suggest the presence of a mechanism involving the central nervous system, not mediated through ACTH release or the renin-angiotensin system, which is important in the physiologic control of aldosterone secretion, and which may involve an inhibitor of aldosterone secretion.

INCREASED PLASMA LEVEL OF RENIN IN EXPERIMENTAL SECONDARY HYPERALDOSTERONISM.

Renal and peripheral venous plasma was prepared for assay of renin by the technique of Helmer and the formed angiotensin II was assayed for both pressor and steroidogenic activity. Both assays showed higher concentrations of renin in both renal and peripheral venous plasma from dogs with thoracic caval constriction than from normal dogs. The increase in aldosterone and corticosterone secretion by isolated adrenals in response to incubated plasma with its formed angiotensin II was qualitatively similar to that observed for synthetic angiotensin II. Thus, the steroid assay provided evidence that the final product formed for assay was angiotensin II. That the pressor activity in renal vein plasma was referable to a substance of renal origin is indicated by the lower level of activity in peripheral venous than in renal venous plasma and the fall in activity in peripheral venous plasma following nephrectomy. Further evidence for the validity of the assay for renin was obtained from studies of renin substrate. A large excess of renin substrate was found in normal dog plasma so that angiotensin II formed by incubation was not limited by substrate exhaustion. Also, the peripheral plasma level of renin substrate was essentially the same in dogs with thoracic caval constriction and in normal dogs.

DEMONSTRATION BY PRESSOR AND STEROIDOGENIC ASSAYS OF INCREASED RENIN IN LYMPH OF DOGS WITH SECONDARY HYPERALDOSTERONISM.

Thoracic duct lymph from normal dogs and from dogs with hyperaldosteronism secondary to thoracic inferior vena caval constriction was assayed for renin. After acidification, dialysis and incubation, lymph from animals with caval constriction showed more angiotensin-like material than lymph of normal dogs when assayed for both pressor and aldosterone-stimulating activities. Nephrectomy was followed by a marked decrease or disappearance of renin activity from lymph. Lymph from dogs with renal venous hypertension secondary to abdominal vena caval constriction did not show increased renin content. Dual assay makes detection of angiotensin II more specific and the findings indicate that increased amounts of renin are released from the kidney into lymph of dogs with experimental secondary hyperaldosteronism.

Effect of temporary thoracic caval constriction on aldosterone secretion in conscious and in anesthetized sheep.

Temporary constriction of the thoracic inferior vena cava of conscious Nareplete sheep was produced by inflation of a Teflon-enclosed rubber cuff. Moderate constriction caused a decrease in the parotid salivary Na/K ratio equivalent to the effect of intravenous infusion of 5–10 μg/hr of Daldosterone. Moderate constriction caused little change in the sheep’s demeanor, cardiac and respiratory rate and blood pressure. Severe constriction produced large effects on these variables and a larger parotid response. The time course of the parotid response indicated rapid increase and decrease of the aldosterone secretion rate with inflation and deflation of the cuff. Infusion of Aldactone at 40 mg/hr blocked the parotid response to moderate caval constriction. Intravenous infusions of mixtures of cortisol and corticosterone at rates approximating maximal adrenal output under ACTH stimulation (5.5 mg/hr and 275 μg/hr. respectively) failed to reproduce the parotid response to thoracic caval constriction. Under anesth...

A critical evaluation of the role of receptors in the control of aldosterone secretion and sodium excretion

Summary Evidence has been considered that arterial baroreceptors influence renal Na excretion via a reflex mechanism which is mediated by an increase in renal sympathetic activity. Such a mechanism might lead to Na retention by either (1) a direct influence of the renal nerves on tubular transport of Na, or (2) indirectly through an increase in renal arteriolar tone and decreased GFR. Available data are inadequate to establish the existence of either mechanism. In fact, there is considerable evidence that the renal nerves exert no direct influence on renal tubular transport. The possibility of arterial baroreceptors which regulate aldosterone secretion has been considered. Extensive denervation of the central arterial tree has failed to provide evidence for such a mechanism. Results from constriction of the common carotid arteries low in the neck indicate that a marked reduction in carotid artery pulse pressure may stimulate ACTH release and a subsequent slight elevation in aldosterone secretion. It seems doubtful that the mechanism has physiologic importance. Evidence is lacking to demonstrate that right atrial stretch receptors are concerned with the regulation of aldosterone secretion. Studies of the hypothalamus and lower brain stem have failed to demonstrate a center for the primary control of aldosterone secretion. Indeed, the striking similarity in the response in aldosterone secretion to bleeding in hypophysectomized and decapitated dogs indicates that the aldosterone stimulating hormone is secreted by an extracranial organ. Failure of nephrectomized-hypophysectomized dogs to show an increase in aldosterone secretion in respose to acute bleeding and the very low rates of aldosterone secretion before bleeding provide evidence for secretion of ASH by the kidney. Also, acute nephrectomy of hypophysectomized dogs with thoracic caval constriction resulted in a marked fall in aldosterone production and saline extracts of kidney showed pronounced aldosterone stimulating activity. The possibility of a receptor in the kidney which responds to a decrease in volume or pressure and leads to release of an aldosterone stimulating hormone by the juxtaglomerular cells was considered.

Aldosterone and corticosterone secretion following midbrain transection.

Following midbrain transection of six normal dogs, secretion rates for aldosterone, corticosterone and Porter-Silber chromogens were not significantly different from values obtained in unoperated dogs; subsequent bleeding increased aldosterone secretion while corticosterone output was unaltered. In five dogs with thoracic caval constriction in which there was a high secretion of aldosterone, midbrain transection was followed by a reduction in inferior vena caval pressure to a level which was apparently too low to sustain the mechanisms resulting in hyperaldosteronism. In one animal aldosterone and corticosterone output was extremely low despite a high venous pressure. In the two dogs with caval constriction in which the venous pressure remained elevated after midbrain transection, the high rate of aldosterone secretion persisted. Bleeding of dogs with caval constriction and midbrain transection resulted in a striking increase in aldosterone secretion. In dogs with caval constriction, corticosterone secretion (5 dogs) and Porter-Silber chromogen output (4 dogs) were high following midbrain transection, and subsequent bleeding failed to increase corticosterone output. It is concluded that complete midbrain transection does not interfere with the high rate of aldosterone secretion which occurs in response to acute blood loss or following caval constriction if venous pressure is maintained at the high control level.