Natriuresis In Response Research Articles

Acute Natriuresis in Response to Calcium Blockade with Tiapamil in Essential Hypertension

Acute Natriuresis in Response to Calcium Blockade with Tiapamil in Essential Hypertension

Natriuretic response of the rat to plasma concentrations of arginine vasopressin within the physiological range.

The relationship of plasma vasopressin concentrations in the physiological range to renal electrolyte excretion was investigated. Unanaesthetized rats, when normally hydrated, were found to have a plasma vasopressin concentration of 1.13 +/- 0.15 mu u./ml. 16 h water deprivation raised this to 1.98 +/- 0.21 mu u./ml. Inactin-anaesthetized rats infused with 0.45% NaCl had a plasma vasopressin concentration of 1.19 +/- 0.18 mu u./ml. Administration of synthetic arginine vasopressin at 6 and 24 mu u./min raised plasma vasopressin levels to 1.88 +/- 0.17 and 4.26 +/- 0.43 microunits./ml respectively. In addition to the expected antidiuresis, vasopressin at a rate of 6 microunits./min also produced a highly significant increase in Na+ excretion from 8.9 +/- 0.6 to 10.5 +/- 0.6 mumol/min and Cl- excretion from 9.1 +/- 0.7 to 10.5 +/- 0.7 mumol/min. At 24 microunits./min it produced larger increases in Na+ and Cl- excretion. Inactin-anaesthetized hypophysectomized rats infused with 0.45% NaCl had a plasma vasopressin concentration of only 0.17 +/- 0.04 microunits./ml. Administration of vasopressin at 6 and 24 microunits./ml raised plasma vasopressin levels in these animals to 0.63 +/- 0.17 and 2.20 +/- 0.11 microunits./ml respectively. Hypophysectomized rats failed to exhibit a natriuresis in response to the lower dose of vasopressin, despite exhibiting an undiminished antidiuresis. The failure of the natriuresis may be related to the lower plasma vasopressin concentration achieved. It is concluded that in the rat plasma vasopressin concentrations within the physiological range do influence Na+ and Cl- excretion by the kidney as well as controlling urine flow rate.

Localization of the cerebroventricular receptors involved in CNS-induced natriuresis.

Ventriculocisternal perfusion (VCP) or localized "push-pull" perfusion (PPP) was performed in pentobarbital-anesthetized dogs. Renal function was studied in protocols consisting of a 1-h experimental period bracketed by 1-h control and recovery periods. The animals were perfused with artificial cerebral spinal fluid (CSF) throughout the protocol but the sodium concentration was elevated (300 mM, high Na) during the experimental period. In the first series of experiments, prior to VCP, petroleum jelly plugs were injected into either the ventral third ventricle (V3V) or other brain regions. When petroleum jelly plugs were injected into the V3V prior to VCP, they prevented perfusates from reaching this area, as determined by subsequent dye perfusion. These V3V plugs blocked the natriuresis and ADH response otherwise induced by high Na VCP. In the second series of experiments, the anterior portion of the V3V (AV3V) was perfused by means of PPP. In some of the PPP experiments a V3V plug was also injected to ensure restriction of the stimulus to the AV3V. PPP of the AV3V with high Na CSF at 50 microliter/min did not induce a natriuresis (either with or without a V3V plug). However, when the high Na CSF was perfused at a very high rate (100 microliter/min) and the stimulus was not restricted to the AV3V by a V3V plug, a natriuresis did occur. These results suggest that the ventricular surface where high Na CSF acts to cause natriuresis and increased ADH secretion is within the V3V region but not in the AV3V.

Furosemide fails to alter plasma active or inactive renin in conscious sheep but does so in anaesthetized animals.

Regulation of plasma levels of active and inactive renin was investigated using sheep with indwelling artery, vein and bladder catheters. Control and experimental studies were carried out in the same animals on different days. Volume depletion during any single experiment was limited to a maximum of 50 ml. Despite large changes in sodium and water excretion, the diuretic furosemide at two dose levels, 1 and 10 mg/kg, failed to alter plasma levels of either active or inactive renin in conscious sheep. Induction of pentobarbitone anaesthesia in the sheep did not, per se, alter either plasma active or inactive renin. Furosemide (10 mg/kg) in anaesthetized animals produced a similar diuresis and natriuresis response to conscious sheep, but plasma active renin increased by 270% and inactive renin decreased to zero. In conscious sheep given an infusion of papaverine, furosemide also produced an increase in plasma active renin and a concurrent decrease in the inactive form. In both anaesthetized animals and in conscious sheep infused with papaverine, furosemide-induced intrarenal vasodilation, as evidenced by changes in clearance of p-aminohippuric acid, was much reduced in comparison to the conscious animals. This may be significant in relation to the control of renin secretion. It appears that the macula densa sodium receptor, which is considered to regulate renin release, will only function after it has been primed by other intra- or extrarenal factors. This is discussed, particularly in relation to the possible role played by the prostaglandin system.

Catecholamine responses to central volume expansion produced by head-out water immersion and saline infusion.

To delineate plasma catecholamine responses to central volume expansion, four salt-replete healthy adults were subjected to 4 h of thermoneutral head-out water immersion (WI) and infusion of 2 liters normal saline (SI) over 4 h on two separate occasions. Each study was preceded and followed by a control hour. Both of these maneuvers resulted in significant increases in urinary sodium excretion and suppression of PRA and plasma aldosterone levels. During WI studies, plasma norepinephrine levels fell steadily from a prestudy value of 453 +/- 74 pg/ml to a nadir of 254 +/- 71 pg/ml (P less than 0.05) during the fourth immersion hour. In response to SI, plasma norepinephrine fell steadily from a prestudy level of 328 +/- 56 pg/ml to a nadir of 261 +/- 47 pg/ml during the fourth hour of infusion. Plasma dopamine levels rose and epinephrine levels were unchanged in response to WI as well as SI. When the mean urinary sodium excretion was plotted against the mean dopamine to norepinephrine ratio, there was a direct relationship in WI studies (r = 0.90) as well as SI studies (r = 0.92). These data suggest that plasma norepinephrine levels fall and plasma dopamine levels rise in response to volume expansion. These data also suggest that relative concentrations of dopamine vs those of norepinephrine may have a role in mediating natriuresis in response to volume expansion.

Attenuated pressure natriuresis in hypertensive rats

We studied the isolated blood-free perfused nonclipped kidneys from the 2-kidney Goldblatt hypertensive rat model (GHR) to evaluate intrinsic excretory responses to changes in perfusion pressure. We examined kidneys from 10 control rats (in vivo systolic BP 110 +/- 3.6 mm Hg), from 9 rats with nonmalignant hypertension (HBP) (in vivo systolic BP 158 +/- 6.5 mm Hg), and from 5 rats with malignant HBP (in vivo systolic BP 183 +/- 6.4 mm Hg). We found that at all levels of perfusion pressure, the renal vascular resistances were significantly higher and glomerular filtration rate (GFR) lower in kidneys from hypertensive rats than in kidneys from control rats. Kidneys from hypertensive rats had lower urinary excretion of sodium (UNaV) and urine flow than kidneys from control rats at all levels of pressure above 100 mm Hg. The most striking differences in all functional parameters were noted in kidneys from rats with malignant HBP. Kidneys from both hypertensive and control rats failed to show changes in vascular resistance in response to Saralasin. We conclude that the nonclipped kidney in GHR exhibits a blunted natriuresis in response to elevated perfusion pressure which occurs in the absence of angiotensin II (AII) and renin substrate. This diminished pressure natriuresis may be caused partly by the lower GFR and by reduced pressure transmission due to greater renal vascular resistance and thus may be partially responsible for the maintenance of the hypertensive state.

Dose-response relation of CSF sodium and renal sodium excretion, and its absence in homozygous Brattleboro rats.

Constant intraventricular infusion (3.3--6.6 microliters/min) of artificial cerebrospinal fluid with sodium concentrations of 100, 150, 200, 250, 300, and 350 mM produced a linear dose-related change in renal sodium excretion in conscious, unrestrained Sprague-Dawley rats. The periventricular receptors stimulated were able to evoke substantial changes in body sodium balance; the 350 mM Na CSF produced an estimated 14% deficit in the content of Na in the extracellular fluid over a 5-hour infusion period. This is the first demonstration of such a dose-response relation over a wide range of CSF Na concentration (above and below normal) in conscious animals. Both the dose-response relation, and the magnitude of the effects, suggests an important physiologic role for this control mechanism. The natriuresis in response to 300 mM sodium infusion was identical in Long-Evans Brattleboro rats heterozygous for diabetes insipidus (DI), and in Sprague-Dawley rats, but was completely absent in homozygous animals. Although the experimental methods (conscious unrestrained rats) precluded simultaneous evaluation of efferent pathways other than antidiuretic hormone (ADH), the evidence from the DI rats suggests that ADH may be the efferent pathway for the response.

Failure of sodium restriction to abolish exaggerated natriuresis in poststreptococcal glomerulonephritis.

Exaggerated natriuresis in response to hypertonic saline infusion occurs with great regularity in patients with documented previous attacks of poststreptococcal glomerulonephritis. Five patients were studied before and after 1 week of dietary sodium restriction in order to examine the possibility that increased extracellular fluid volume might play a role in the response to acute saline infusion. Plasma renin activity (PRA) and PRA responsiveness to sodium depletion were normal, suggesting that extracellular fluid volume was not increased. In all patients, extracellular fluid volume decreased during sodium restriction, as judged by weight loss, cumulative negative sodium balance, small decreases in measured plasma volume, and appropriate increases of PRA and plasma aldosterone concentration. Hypertonic saline infusion provoked exaggerated natriuresis in all patients equally as well after dietary sodium restriction as before. Exaggerated natriuresis in poststreptococcal glomerulonephritis occurs without evidence of chronic expansion of extracellular fluid volume and is not affected by reduction of extracellular fluid volume.

Effects of hypotonic expansion on sodium and water excretion in hypertensive non-pre-eclamptic gravidas

The occurrence of exaggerated natriuresis in response to volume expansion in hypertensive gravidas is controversial. In the present study, renal response to hypotonic saline infusion of 7 hypertensive pregnant women was compared to results of identical studies in normal gravidas. Additionally, the effect of changing from lateral to supine recumbency, a potent antinatriuretic maneuver, was evaluated. The hypertensive patients handled short-term saline loads in a manner similar to that observed in normotensive pregnant women, and changing posture resulted in a similar antinatriuretic effect in both groups. Thus, assessment of the natriuretic system by two different methods failed to demonstrate an exaggerated natriuresis in pregnant hypertensive women. Furthermore, patterns of solute and water excretion showed no evidence of impaired sodium handling at distal tubular sites, in contrast with observations in nonpregnant hypertensive women.

The source and chemical nature of the natriuretic activity of plasma evoked by saluretic "volume reflexes".

The evidence that the natriuresis in response to such hemodynamic alterations as infusion of saline or blood and carotid occlusion is related to the appearance of a natriuretic activity in the plasma was reviewed. This activity, which can be assayed by tubular rejection of sodium in the hydrated ethanol-anesthetized rat or chloralosed cat, or by the zero potential current method in frog skin, was most prominent in blood from the internal jugular vein and then the femoral artery; no such activity was found in blood from the renal or femoral veins. It was therefore postulated that this activity is of cerebral origin. Extracts of posterior bovine hypothalamus when treated with proteolytic enzymes first showed an antinatriferic action, which disappeared on longer incubation. This activity is presumably contained in a polypeptide which is present in a larger "hormonogen" molecular form in the posterior hypothalamus; destruction of the posterior hypothalamus results in renal loss of sodium. Some questions remain: are the natriuretic and antinatriferic activities properties of the same substance; and do the activities that have been obtained from the posterior hypothalamus and plasma represent the same substance?

Effects of metaraminol perfusion of kidney, liver, or brain on renal response to saline infusion in the dog.

SummaryThe exaggerated natriuretic response to infusion of saline observed in hypertensive man or dog might be related to vaso-constriction within some key organ rather than to elevation of blood pressure. To examine this thesis saline infusion was administered to 16 mongrel dogs while individual organs were perfused with suppressor doses of metar-aminol. The dose of metaraminol was that which the organ would receive during a systemic pressor infusion known to result in exaggerated natriuresis in the dog. The local pharmacologic effects of metaraminol on kidney, liver or brain did not result in an augmented natriuretic response to the infusion of saline. These data are therefore consistent with the view that hypertension itself is necessary for the appearance of exaggerated natriuresis in response to saline infusion in the dog.

Augmented Natriuretic Response to Acute Sodium Infusion Following Blood Pressure Elevation with Metaraminol in Normotensive Subjects.

Excerpt It is well-established that patients with essential hypertension have an exaggerated natriuresis in response to acute intravenous administration of sodium. While the mechanism for this rema...

Effect of Aldosterone Antagonist (Spironolactone) on Patients with Severe Congestive Heart Failure

Spironolactone was evaluated as a diuretic in the therapy of six patients with chronic severe congestive heart failure, during which metabolic balance studies were performed. Two of the patients showed a clear-cut although moderate diuresis and natriuresis in response to spironolactone in the presence of other diuretics. Two patients had slight unsustained responses and two showed no response. No significant change in potassium excretion was observed. A decrease in the serum sodium level was noted in four patients, associated with a rise in serum potassium. Urinary aldosterone excretion was normal or low in all patients and showed no correlation with the diuretic response to spironolactone.It is concluded that spironolactone has definite but limited usefulness in the therapy of some but not all patients with chronic congestive heart failure.