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H Sonnenberg

Publications and source records attributed to H Sonnenberg.

At least 73 records · Page 4Linked to original sources
PubMed1986

Mechanisms of release and renal tubular action of atrial natriuretic factor.

Inasmuch as atrial natriuretic factor (ANF) is apparently involved causally in the renal response to acute hypervolemia, it became of interest to study cellular mechanisms of release and renal tubular action. To study release mechanisms, freshly excised rat heart atria were incubated in vitro. Activation of the cellular adenylate cyclase system by either beta-adrenergic stimulation or the vasopressin analog deamino-8-D-arginine vasopressin did not result in ANF release. By contrast, activation of the polyphosphoinositide system by alpha-adrenergic stimulation or stimulation of the V1-type vasopressin receptors, and by a calcium ionophore or active phorbol ester, significantly increased natriuretic activity in the medium and reduced it in tissue. It is concluded, therefore, that activation of this latter system is the mechanism for ANF secretion from atrial myocytes. To test the effect of ANF on tubular transport in the medullary collecting duct, microcatheterization was used in rats before and during i.v. infusion of synthetic atrial peptide (23 amino acids). It was found that tubular delivery of salt to this part of the nephron was increased, and that reabsorption in the duct itself was reduced. In control experiments, increased delivery was associated with proportionately increased reabsorption, which demonstrated glomerulotubular balance in the nephron segment under normal conditions. The natriuretic effect of ANF, therefore, was not caused solely by enhanced tubular load, but included specific inhibition of duct sodium reabsorption as an essential feature of the renal response.

Absorption↗
PubMed1986

Development of a test to evaluate the transtubular potassium concentration gradient in the cortical collecting duct in vivo.

The purpose of these investigations was to develop a noninvasive test to estimate the transtubular potassium concentration gradient (TTKG) and thereby aldosterone action in the late distal convoluted tubule and the cortical collecting duct in patients with disorders of potassium excretion. Experiments were performed in rats under conditions where the ratio of urine to renal venous potassium concentration could reflect this TTKG. A large furosemide-induced diuresis ensured that sodium delivery was adequate and minimized the change in water content during transit through the medullary collecting duct (equal osmolality and TF/P inulin at the base and the tip of the medullary collecting duct). There was no significant potassium reabsorption nor secretion during transit through the medulla as shown by micropuncture and microcatheterization. Thus the potassium concentration in the urine should mirror that in the lumen at the major nephron sites of potassium secretion. The potassium concentration in the renal vein provides the simplest estimate of the cortical peritubular potassium concentration (the mean renal A-V difference for potassium was 1.2 mM); with a very high fractional excretion of potassium, an adjustment can be made to the arterial potassium concentration to correct for the potassium extracted. If the urine/plasma potassium concentration ratio were a quantitative reflection, then the transepithelial potential difference (TEPD) would be close to -40 mV in normal rats. The TTKG fell to unity when amiloride was given, consistent with an abolition of the apparent TEPD in vivo by this drug. Similar results were obtained in non-diuretic rats. The clinical implications of these findings are discussed.

Aldosterone↗
PubMed1985

Atrial natriuretic factor--a new hormone affecting kidney function.

A family of biologically active peptides (atrial natriuretic factor - ANF) has recently been identified in mammalian heart atria. The peptides derive from a common 152 amino acid precursor and at least 1% of total messenger RNA activity is specific for the factor. When injected intravenously ANF is hypotensive and natriuretic. Data indicate that atrial natriuretic factor represents a newly discovered hormone involved in the regulation of blood pressure and volume. Cellular release of ANF does not require the activation of the adenylate cyclase system, but is associated with receptor-mediated activation of the cellular polyphosphoinositide mechanism. The natriuretic effect includes increased glomerular filtration rate and specific inhibition of normal sodium reabsorption from the medullary collecting duct. The mechanism of this transport inhibition is not yet known.

Animals↗
PubMed1985

Inactivation of atrial natriuretic factor in blood.

Tissue extracts of rat heart atria contain a family of peptides with natriuretic and vasorelaxant properties. It has been shown by others that inactivation of this atrial natriuretic factor may involve endogenous peptidases. The present experiments demonstrate that incubation in blood in vitro reduces the natriuretic activity of the factor. Specifically, inactivation was associated with a white cell/platelet fraction, indicating that these blood elements may play a physiological role in the metabolism of this new putative hormone.

Animals↗
PubMed1984

Cellular mechanism of release of atrial natriuretic factor.

Tissue extracts of rat heart atria contain a family of peptides with natriuretic and vasorelaxant properties. We have shown previously that this "atrial natriuretic factor" may be released in vitro from incubated atria by muscarinic cholinergic stimulation. Experiments reported here demonstrate that incubation with adrenalin or arginine vasopressin, but not with deamino-8-D-arginine vasopressin, also results in liberation of atrial natriuretic factor. Since the effective agonists have in common activation of the cellular polyphosphoinositide system with consequent production of inositol triphosphate, we suggest that inositol triphosphate is the second messenger of stimulus-secretion coupling in atrial cells.

Animals↗
PubMed1984

Cardiovascular effects of atrial extracts in anesthetized rats.

Tissue extracts derived from atria or ventricles of Sprague-Dawley rats were injected into Inactin-anesthetized assay rats. Compared with ventricular extracts, atrial extracts produced a 20 mmHg (1 mmHg = 133.322 Pa) fall in mean arterial blood pressure. This fall resulted from failure to increase cardiac output in compensation for peripheral vasodilation. Two factors were responsible: depression of heart rate (by 25 beats/min) and failure to increase cardiac performance. The time patterns and magnitudes of changes in cardiovascular parameters after cardiac extracts were not changed by prior atropinization. However, assay rats that were vagotomized showed no cardiac slowing after atrial extract and showed a significantly smaller decrease in mean arterial blood pressure than did sham-vagotomized or intact rats. Another group of assay rats was vagotomized as well as carotid-sinus-denervated before extract injection. In these rats the degree of hypotension caused by atrial extract was significantly greater than that observed after vagotomy alone and was not significantly different from that observed in rats with intact innervation. The results suggest that the hypotension that is caused by atrial extract, but not by ventricular extracts, results in part from the reflex effects of direct stimulation of chemosensitive cardiopulmonary receptors with vagal afferents and partly from the reflex effects of baroreceptor unloading. Ventricular extract had no hypotensive effect in any group of assay rats.

Animals↗
PubMed1984

Right atrial appendectomy reduces the renal response to acute hypervolemia in the rat.

We have shown previously that an extract of atrial tissue from rat heart contains a potent natriuretic factor. In this study anesthetized rats were connected to a respirator and the right atrial appendage was either excised, using a loop ligature (experimental group), or the loop was placed around the appendage and then removed (sham-operated group). After equilibration and control urine collection periods an isooncotic Ringers-albumin solution was infused intravenously (25% of estimated blood volume), and renal function was monitored over the next hour. There were no differences between groups in control period arterial or central venous pressures, heart rates, cardiac outputs, renal blood flows, or filtration rates. However, the diuretic and natriuretic responses to infusion in the experimental group were only one half of those in the sham-operated series (vol = 23.4 +/- 6.2 vs. 68.2 +/- 11.0 microliter X min-1 X g kidney wt-1, UNa V = 2,731 +/- 856 vs. 6,504 +/- 962 nmol X min-1 X g kidney wt-1). These differences were not affected by prior bilateral vagotomy. Administration of homologous atrial natriuretic factor or furosemide resulted in identical renal responses in both groups. We conclude therefore that acute hypervolemia is associated with release of atrial natriuretic factor into the bloodstream and that removal of the atrial appendage reduces the amount available for such release.

Acute Disease↗
PubMed1983

Thiazide diuretic effect on medullary collecting duct function in the rat.

The distal convoluted tubule is thought to be the principal site of action of thiazide diuretics, but, to our knowledge, there are no studies of their possible effects on collecting duct transport. Microcatheterization of the inner medullary collecting duct (IMCD) was carried out in rats undergoing a modest diuresis, natriuresis, and chloriuresis from hydro-chlorothiazide (2 mg/kg/hr) and in normal controls. Delivery of fluid, sodium, and chloride to the beginning of the IMCD was increased, but not significantly, while the load remaining at the papillary tip (end) of the duct was increased markedly by hydrochlorothiazide. Chloride reabsorption in the IMCD was affected most markedly; the chloride reabsorption between the beginning and end of the duct, as a fraction of the delivered load, was reduced from 70.4 +/- 5.4% in controls to insignificant amounts with hydrochlorothiazide (8.2 +/- 11.5%, P less than 0.001). The fraction of delivered sodium reabsorbed along the collecting duct was decreased from 78.5 +/- 4.9% in controls to 37.2 +/- 12.4% (P less than 0.005) in thiazide-treated rats and fluid reabsorption was decreased from 59.4 +/- 4.0% in controls to 31.9 +/- 5.1% (P less than 0.005). Small but significant potassium secretion into the IMCD occurred with hydrochlorothiazide, probably secondary to the marked increase in potassium delivery to the duct. Increased potassium excretion could account for a maximum of 50% of chloriuresis with hydrochlorothiazide. The observation that thiazide diuretics decrease chloride, sodium, and fluid reabsorption in the medullary collecting duct, like the recently demonstrated inhibitory effect of furosemide on this nephron segment, has significant implications for the rationale for diuretic use.

Animals↗
PubMed1983

The effect of a natriuretic atrial extract on renal haemodynamics and urinary excretion in anaesthetized rats.

1. An extract of cardiac atrial tissue, when injected intravenously into anaesthetized rats, caused a large and rapid increase in renal excretion of sodium chloride. 2. The renal response to atrial extract was associated with increases in total and medullary blood flow in the kidney, as measured by microsphere and albumin uptake methods, respectively. 3. The data suggest that these changes in renal haemodynamics may contribute to, but are unlikely to be the complete cause of, the natriuresis and chloriuresis following injection of atrial tissue extract.

Albumins↗
PubMed1983

Natriuretic effect of atrial extract on isolated perfused rat kidney.

To examine the mechanisms underlying the natriuretic action of a partially purified extract of rat atria (AE) we injected the equivalent of one atrium into isolated perfused rat kidneys. Some kidneys received an infusion of angiotensin II at 0.5 ng/min throughout the experiment. In the absence of angiotensin AE had a variable effect on renal vascular resistance (RVR) but, in the presence of angiotensin II, AE consistently decreased RVR by 3% for 5 min followed by a slight increase. Inulin clearance and filtration fraction increased slightly but significantly. AE increased sodium, chloride, phosphate, and free water clearance but not potassium excretion. Ventricular extract had no effect on any of these variables. Furosemide (50-250 micrograms) increased sodium, chloride, and potassium but not phosphate or free water excretion. AE did not alter dopamine or norepinephrine excretion. We conclude that AE increases the glomerular filtration rate (GFR) and inhibits tubular reabsorption by mechanisms which differ, at least in part, from those affected by furosemide.

Animals↗
PubMed1983

Furosemide action on collecting ducts: effect of prostaglandin synthesis inhibition.

The effect of furosemide on inner medullary collecting duct chloride reabsorption has not been determined, and the blunting of furosemide action by drugs that inhibit prostaglandin synthesis, while known to occur, has not been examined in detail. The effect of indomethacin and meclofenamate on furosemide diuresis was studied in the rat using clearance and collecting duct microcatheterization methods. Furosemide-treated control animals showed complete inhibition of chloride, sodium, and water reabsorption in the inner medullary collecting duct. Rats given indomethacin or meclofenamate before and during furosemide administration showed marked reduction of the chloriuresis, natriuresis, and diuresis. Reduced delivery of sodium and chloride to the beginning of the inner medullary collecting duct, associated with a decrease in glomerular filtration rate and increased reabsorption in more proximal nephron segments, was largely responsible for the reduced natriuresis and chloriuresis during inhibition of prostaglandin synthesis. In addition, indomethacin increased collecting duct NaCl reabsorption toward normal, but meclofenamate showed no such effect. The results indicate that furosemide inhibits medullary collecting duct reabsorption of chloride, sodium, and water in the rat. The blunting of diuretic action seen with inhibition of prostaglandin synthesis is largely, although not entirely, due to effects of indomethacin and meclofenamate on furosemide action at nephron sites proximal to the collecting duct.

Animals↗
PubMed1982

Prostaglandin synthesis inhibition during volume expansion: collecting duct function.

The aim of this study was to examine the possible role of renal prostaglandins in the response of the inner medullary collecting duct (IMCD) to acute volume expansion. Collecting duct microcatheterization and clearance studies were carried out in anesthetized rats, volume-expanded with isotonic Ringer's solution. In volume-expanded control animals, there was no significant sodium or chloride reabsorption between the beginning and end (papillary tip) of the IMCD. Administration of indomethacin or meclofenamate prior to and during volume expansion in two other groups of rats resulted in significant water, sodium, and chloride reabsorption along the IMCD and markedly blunted the diuretic, natriuretic and chloriuretic response to volume expansion. Because delivery to the beginning of the duct was not significantly decreased, enhanced reabsorption in the IMCD largely accounted for the decrease in natriuresis and chloriuresis. Inner medullary tissue fluid chloride concentration increased after inhibition of prostaglandin synthesis. The results indicate that renal prostaglandins, perhaps by directly decreasing sodium chloride reabsorption, have an important role in the decrease in collecting duct reabsorption of sodium and chloride observed with acute volume expansion.

Animals↗
PubMed1982

Effect of acute unilateral renal denervation on intrarenal haemodynamics and urinary excretion in rats before and during hypervolaemia.

1. The possible involvement of renal nerves in the diuresis and natriuresis of blood volume expansion was studied in anaesthetized rats. Acute unilateral renal denervation caused increased excretion of fluid, sodium and potassium. 2. Renal blood and plasma flows were elevated without change in filtration rate. Intracortical blood flow distribution was not affected by the denervation. 3. Blood infusion caused diuresis, natriuresis and kaliuresis in both denervated and sham-denervated kidneys, associated with comparable initial increases in filtration and decreases in renal blood flow. No change in flow distribution was found, whether or not renal nerves were intact. 4. Although the magnitude of the excretory response to hypervolaemia was greater in denervated kidneys, the temporal pattern was identical with that of sham-operated kidneys. Our data thus do not show an effect of efferent renal nerve activity on volume natriuresis.

Animals↗
PubMed1982

Urea handling by the distal tubule and collecting duct of the rat during urea--saline, isotonic saline, or urea diuresis.

The aims of the present study were to examine the effects of urea and isotonic saline loads separately and together on urea handling in the medullary collecting duct and surface distal tubules of the rat kidney. Microcatheterization of the medullary collecting duct during isotonic saline diuresis (saline at 5% of body weight per hour, plasma urea 4.3 mM/L), showed an increase in the remaining fraction of filtered urea from 56.2% at the beginning (corticomedullary junction) to 68.5% at the end (papillary tip) of the medullary collecting duct (n = 17 paired samples in six rats, p less than 0.05). There was no change in the fraction of filtered urea along the medullary collecting duct during urea diuresis (plasma urea 87 mM/L, n = 15 paired samples in six rats) or during urea--saline diuresis (plasma urea 103 mM/L, n =32 paired samples in nine rats). Micropuncture of surface distal tubules in the same animals showed an increase in the fraction of filtered urea between end-distal samples and the beginning of the medullary collecting duct from 28.9 to 56.2% during isotonic saline diuresis (p less than 0.001), and from 53.6 to 75.3% during urea--saline diuresis (p less than 0.01), but no change during urea diuresis (63.6 to 60.0%, p = NS). Our conclusions are as follows. (1) Urea entry into the medullary collecting duct during steady-state diuresis occurs at low intratubular urea contractions (isotonic saline diuresis) but not at high concentrations (urea--saline diuresis and urea diuresis). (2) Urea entry between the surface distal tubule and the beginning of the medullary collecting duct occurs during saline diuresis (isotonic saline diuresis and urea--saline diuresis) but not urea diuresis. The latter finding suggests that isotonic saline loads affect urea transport differently in juxtamedullary nephrons compared to superficial nephrons.

Animals↗
PubMed1982

Lack of effect of barbiturate and ketamine anesthesia on renal blood flow in chronically instrumented rats prepared for micropuncture.

Fifteen-micrometer microspheres were used to study renal blood flow in rats which had been cannulated 3 or more days previously. Renal blood flow was assessed while the animals were conscious, after induction of anesthesia with inactin, pentobarbital, or ketamine, and after preparation for renal micropuncture. Blood pressure fell with anesthesia when barbiturates were used and was restored by tracheostomy. In conscious rats, right and left renal blood flows averaged 4.70 +/- 0.24 and 4.64 +/- 0.23 mL/min per gram kidney weight, respectively. These values were essentially unchanged following anesthesia with all agents used and they were also unaffected by surgery. We conclude that, in chronically prepared rats, renal blood flow is not affected by anesthesia or by micropuncture surgery.

Anesthesia↗
PubMed1982

Intrarenal localization of the natriuretic effect of cardiac atrial extract.

In anesthetized rats micropuncture and microcatheterization were used to collect tubular fluid from end proximal and distal tubules and from the outer medullary collecting duct. Urine was collected at the papilla tip. Samples were taken from the same sites before and after intravenous injection of atrial tissue extract; rats injected with ventricular extract served as controls. Sodium excretion increased 17-fold after atrial extract, a significantly greater rise than the 3-fold increase after ventricular extract. Clearances of inulin and single nephron filtration rates did not change significantly in either group. Tubular fluid collection results showed a similar reduction (16 to 20%) of proximal fluid and sodium reabsorption in both groups. In the experimental group only, NaCl reabsorption failed to rise in response to increased load in the medullary collecting duct. The resulting fall in fractional reabsorption in the medullary collecting duct accounted for 80% of the natriuresis. We conclude that atrial tissue from rat hearts contains a factor which causes increased renal NaCl excretion by inhibiting transport in the medullary collecting duct.

Animals↗