Biomedical subjects

H Sonnenberg

Publications and source records attributed to H Sonnenberg.

At least 37 records · Page 2Linked to original sources

PubMed1995

Potassium depletion and salt-sensitive hypertension in Dahl rats: effect on calcium, magnesium, and phosphate excretions.

Weanling male inbred Dahl rats (Jr salt-sensitive (S) and salt-resistant (R) strains) were placed on high (4%, HK) and low (0.2%, LK) potassium diets for 4 weeks. Both diets contained 8% sodium chloride, 2.5% calcium, 0.8% magnesium, and 2.0% phosphorous. Balance studies were carried out during the final week on the diets. Mean arterial blood pressure was determined, and dietary intake and urinary output of water, sodium, chloride, potassium, calcium, magnesium, and phosphate were monitored daily during this period. The data show that blood pressures of S rats were significantly higher than those of R rats on both HK and LK diets; however, reduced dietary potassium was associated with increased blood pressure in both strains. Urinary excretions of calcium and magnesium were higher, and urinary phosphate excretion was lower, in S compared to R rats. Decreased potassium intake was associated with increased excretion of calcium, magnesium and phosphate in both strains. The changes in calcium and magnesium excretion were significantly correlated to blood pressure across strains and diets. We conclude that the effects of a high salt diet on increasing blood pressure can be potentiated by lack of potassium, even in previously salt-resistant rats. Increased blood pressure is associated with increased divalent cation excretion. It is not yet known whether this is a cause-and-effect relationship.

Animals↗

PubMed1995

Effect of renal perfusion pressure on excretion of calcium, magnesium, and phosphate in the rat.

Abnormalities in renal handling of calcium, magnesium, or phosphate have been implicated in the development and/or maintenance of human hypertension. We have shown recently that renal excretion of these ions is correlated to blood pressure in Dahl salt-sensitive as well as salt-resistant rats. The present study was designed to determine whether renal perfusion pressure per se could affect excretion of these ions. Urinary excretion of calcium, magnesium, and phosphate was studied in anaesthetized Sprague-Dawley rats under basal conditions and during an intravenous infusion of angiotensin II (ANG II), vasopressin (AVP) or phenylephrine (PE). A cuff, placed around the aorta between the two renal arteries, allowed maintenance of normal perfusion pressure in the left kidney, while that in the right kidney was allowed to rise. Infusion of pressor agents raised mean arterial blood pressure to comparable levels (means +/- SE): ANG II (n = 7), before = 102 +/- 4, during = 133 +/- 3 mmHg, AVP (n = 8), before = 110 +/- 7, during = 136 +/- 5 mmHg, PE (n = 6), before = 111 +/- 6, during = 141 +/- 6 mmHg. Although there was no difference in excretion of calcium, magnesium and phosphate between the two kidneys under basal conditions, infusion of ANG II or PE induced hypercalciuria, hypermagnesiuria and hyperphosphaturia in the right kidney which was exposed to the increased arterial pressure. Such effects did not appear in the pressure-controlled left kidney. Infusion of AVP was associated with reduced excretion of calcium and magnesium, and increased excretion of phosphate, in the normotensive kidney. The response to the similarly increased renal perfusion pressure in this group was also reduced for calcium and magnesium, and enhanced for phosphate. The results indicate (1) renal excretion of calcium, magnesium and phosphate is renal perfusion pressure-dependent; the higher the renal perfusion pressure, the greater the excretion of these ions. (2) Independently of perfusion pressure, AVP can inhibit phosphate reabsorption and stimulate divalent cation reabsorption.

Angiotensin II↗

PubMed1994

Lack of biologic activity or specific binding of amino-terminal pro-ANP segments in the rat.

In addition to atrial natriuretic peptide (ANP99-126) itself, linear peptide fragments from its N-terminal prohormone segment (pro-ANP) have been reported to have biological activity. In vivo, diuresis and natriuresis, as well as hypotension have been observed. In vitro, sodium uptake into medullary collecting duct cells was inhibited, and tone of vascular smooth muscle was reduced, associated with activation of guanylate cyclase. Such previous studies have used heterologous peptides and species, e.g., human pro-ANP1-30 or pro-ANP31-67, tested in rat, pig, or dog. The present experiments were designed to test whether rat pro-ANP1-30 or pro-ANP31-67 were natriuretic and hypotensive in rats, whether the two peptides showed specific binding to plasma membranes from rat kidney cortex or aorta, and whether they affected particulate guanylate cyclase activity in rat glomerular membranes. To extend in vitro results from the literature, the effect of human pro-ANP31-67 on transport in the rat medullary collecting duct in vivo was also tested. Although rat ANP99-126, as expected, increased diuresis and natriuresis, associated with inhibition of transport in the medullary collecting duct, in identically treated rats human pro-ANP31-67 was without effect. Similarly, only the ANP99-126 infusion resulted in reduction of arterial blood pressure. Furthermore, no diuretic, natriuretic, or hypotensive responses were observed in rats infused with either rat pro-ANP31-67 or pro-ANP1-30. In plasma membranes from rat kidney cortex or aorta, neither of the rat prosegments showed specific binding, or interference with ANP99-126 receptors. Finally, in contrast to ANP99-126, neither of the prosegments was able to increase basal guanylate cyclase activity in rat glomerular membranes. Therefore, under our experimental conditions we were unable to replicate the earlier results. This study thus does not support a regulatory role for pro-ANP fragments in blood volume or blood pressure homeostasis.

Amino Acid Sequence↗

PubMed1994

Cardiovascular and renal functional effects of an antagonist of the guanylyl cyclase-linked ANF receptor.

A selective antagonist for the cGMP-linked ANF receptor was used to assess inhibition of cardiovascular and renal actions of atrial natriuretic factor (ANF). Two groups of anesthetized rats were injected with antagonist or vehicle, respectively, prior to an infusion of ANF. A third group received neither antagonist injection nor ANF infusion and served as a time control. Compared to ANF infusion alone, prior antagonist administration was associated with significant reduction of both the hypotension and hemoconcentration following peptide infusion, although significant residual effects were still present. Glomerular filtration rates during ANF infusion were significantly lower in the antagonist group. The increases in urinary salt and water excretion were also partially blocked by the antagonist. Microcatheterization studies showed significant partial reversal of ANF-induced inhibition of sodium chloride and water reabsorption in the medullary collecting duct. We conclude that the antagonist is an effective specific blocker of the cardiovascular, renal hemodynamic, and tubular effects of ANF, providing a useful new tool to elucidate the regulatory roles of this peptide hormone system.

Animals↗

PubMed1994

Dietary salt extremes and renal function in rats: effect of atrial natriuretic factor.

1. Chronic reduction of salt intake can reduce the natriuretic effect of exogenously administered atrial natriuretic factor. The purpose of this study was to elucidate the intrarenal site(s) of such atrial natriuretic factor resistance. Renal clearance and collecting duct microcatheterization experiments were made before and during infusion of atrial natriuretic factor in three groups of rats: group 1 consisted of rats fed a high salt diet (8% NaCl) for 1 week before the experiment; group II were fed a low salt diet (< 0.008%); group III received the same low salt diet, but were acutely replenished with salt at the time of experiment. 2. Baseline sodium chloride excretion was 6480 +/- 810 nmol min-1 g-1 kidney weight in group 1 compared to 99 +/- 16 in group 1. Fractional reabsorptions in the medullary collecting duct were 37 +/- 6% and 95 +/- 2% of delivered load, respectively (P < 0.05). The fractions of filtered sodium remaining at the beginning of the medullary duct were 6.6 +/- 1.0% of filtered load in group 1 and 2.7 +/- 0.7% in group II (P < 0.05), indicating increased tubular reabsorption in group II, not only in the medullary duct, but also in upstream nephron segments.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗

PubMed1994

Proximal tubular function in transgenic mice overexpressing atrial natriuretic factor.

A transgenic mouse model in which atrial natriuretic factor (ANF) expression is targeted to the liver was used to study intrarenal adjustments to the chronically elevated hormone level. Such animals, designated TTR-ANF, are characterized by reduced arterial blood pressure but similar sodium excretion compared with nontransgenic siblings. Proximal tubular micropuncture gave the following results: single-nephron filtration rate = 12.7 +/- 1.1 vs. 15.6 +/- 1.9 nL/min (TTR-ANF versus nontransgenic, ns); end-proximal tubular fluid/plasma concentration ratio of inulin = 1.93 +/- 0.09 vs. 1.97 +/- 0.15 (ns); fractional reabsorption of sodium = 45.5 +/- 2.8 vs. 46.0 +/- 3.8% (ns); fractional reabsorption of chloride = 33.6 +/- 3.3 vs. 32.4 +/- 4.1% (ns). These data indicate that life-long elevation of plasma ANF concentration was not associated with significant alteration in single-nephron filtration rate and proximal tubular function. We conclude that compensatory antinatriuretic mechanisms, localized downstream from the proximal tubule, can prevent ANF natriuresis.

Animals↗

PubMed1994

Effect of bradykinin B2 receptor antagonist and indomethacin on natriuretic and hypotensive responses to atrial natriuretic factor.

The effects of inhibition of bradykinin and prostaglandin on the renal and blood pressure responses to atrial natriuretic factor (ANF) were studied in anesthetized rats. Intraarterial infusion of the receptor antagonist D-Arg[Hyp3,Thi5,8,D-Phe7]bradykinin (BKA) at 14 micrograms/min, a rate sufficient to block the hypotensive response to 250 micrograms of bradykinin, did not affect the natriuresis due to injection of ANF (UNaV: control, before ANF, 393 +/- 101, after ANF, 2322 +/- 400 nmol/min; BKA, before ANF, 261 +/- 72, after ANF, 2259 +/- 390 nmol/min). In contrast, infusion of indomethacin (Indo) reduced the level of sodium excretion both before and especially after ANF administration (UNaV: Indo, before ANF, 75 +/- 15, after ANF, 320 nmol/min). The effect of combining BKA with Indo was not different from the effect of Indo alone (UNaV: BKA + Indo, before ANF, 119 +/- 26, after ANF, 469 +/- 167 nmol/min). The bradykinin antagonist, with or without Indo, was associated with significant hypotension relative to control. Indo, both in the absence and presence of the antagonist, was associated with a progressive decrease in blood pressure compared with control. However, in each the hypotensive responses to ANF were not different from those in the control group. We conclude that under the present experimental conditions bradykinin does not modify ANF-induced natriuresis. However, inhibition of prostaglandin synthesis by Indo is associated with renal salt retention, reducing natriuresis both before and after ANF administration.

Animals↗

PubMed1994

Blood pressure regulation in ANF-transgenic mice: role of angiotensin and vasopressin.

Transgenic mice overexpressing a transthyretin promoter-ANF structural fusion gene have a life-long reduction in arterial blood pressure compared to nontransgenic littermates. The present study was designed to test the hypothesis that the high plasma level of ANF in the transgenic mice inhibits the renin-angiotensin and/or vasopressin systems, thereby causing the hypotension. Mice were anaesthetized with Inactin and arterial pressure and heart rate were monitored before and during Saralasin infusion and vasopressin V1 receptor blockade. Effectiveness of the blockade was determined by injection of angiotensin and vasopressin before and during Saralasin and V1 receptor antagonist administration. Saralasin was associated with hypotension in both transgenic and nontransgenic mice. The decrease in blood pressure was proportionally greater in the transgenic animals. Vasopressin receptor blockade had little effect on blood pressure in either group. Heart rates were not different between the groups during any maneuver. We conclude that the chronic hypotensive effect of ANF overproduction does not involve the inhibition of either renin-angiotensin or vasopressin systems. The data, however, suggest that the renin-angiotensin system may be stimulated in the ANF-transgenic mice.

Angiotensin II↗

PubMed1992

Effect of potassium infusion on renal function in ANF-transgenic mice.

Transgenic mice expressing an ANF fusion gene in the liver were used to study renal function before and during an intravenous KCl load. These animals are characterized by a 10- to 20-fold elevation in plasma ANF concentration, and by a reduction in arterial blood pressure by 20-30 mm Hg, compared to nontransgenic littermates. Before the KCl infusion, renal excretions of fluid, sodium, potassium, and chloride were not different from corresponding values in the nontransgenic sibling mice. Glomerular filtration rates were slightly lower in the transgenic animals. During the KCl infusion, diuresis, saluresis, and kaliuresis were found in both groups. However, salt and water excretion, but not potassium excretion, were significantly greater in the transgenic group. In a separate series, plasma aldosterone concentrations were significantly higher in the transgenic, compared to the nontransgenic mice. These data are interpreted as indicating that antinatriuretic mechanisms, including aldosterone-dependent sodium reabsorption in the cortical collecting tubule, can counteract the effect of ANF to inhibit sodium reabsorption in the medullary duct system, thus allowing maintenance of salt balance. Furthermore, a reduced tubular flow rate at the aldosterone-sensitive site would ensure normal potassium excretion despite the elevated mineralocorticoid level. During KCl infusion, the known increase in tubular delivery of salt and water to the duct would allow full expression of the downstream ANF effect, accounting for the relatively greater diuresis and saluresis in the transgenic mice. We conclude that both renal and adrenal actions of ANF can be rendered ineffective by countervailing mechanisms, suggesting an explanation for the apparent lack of biological activity of endogenously elevated plasma NAF in some disease states.

Aldosterone↗

PubMed1991

Renal response to blood volume expansion in Brattleboro rats after acute treatment with vasopressin.

The renal response to iso-oncotic blood volume expansion with bovine serum albumin was studied in anaesthetized homozygous Brattleboro (DI) rats after acute (1 day) pretreatment with 1 U arginine-vasopressin (AVP) compared to heterozygous controls. In AVP-treated DI (DI + AVP) rats, basal urine flow as well as urinary sodium, chloride, and potassium excretion, were not different from controls. Diuresis and kaliuresis induced by volume expansion were blunted in DI + AVP rats. However, natriuresis and chloruresis were exaggerated in DI + AVP rats. They increased faster, reached a higher maximum, but declined earlier, compared to controls. The blunted diuresis resulted in a positive volume balance by the end of the experiment in DI + AVP rats, whereas the controls showed restoration of normal balance. Significant retention of sodium and chloride was observed in controls, but not in DI + AVP rats, over the time of the experiment. DI + AVP rats lost significantly less potassium than controls during the experiment. As judged from the lithium clearance method, the exaggerated saluresis in DI + AVP rats was mainly due to a reduced proximal sodium reabsorption. Plasma immunoreactivity of atrial natriuretic peptide (ANP) rose during blood volume expansion and fell in the recovery period. It was not different between AVP-treated DI rats and controls at any time of the experiment. Inulin clearance was slightly, but not significantly, lower in DI + AVP rats and increased after blood volume expansion in DI + AVP rats only.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

The effect of isoproterenol on fluid and electrolyte transport in the inner medullary collecting duct.

In the late distal and cortical collecting tubule, which is the principal regulatory site for potassium (K) excretion, vasopressin stimulates, and epinephrine via beta-adrenergic action, inhibits K secretion. In the inner medullary collecting duct (IMCD) we have shown that vasopressin also stimulates K secretion. The present experiments were designed to determine whether the beta-adrenergic agonist, isoproterenol, would induce K reabsorption in the IMCD, and (or) prevent a secretory response to acute KCl infusion. Two groups of rats, with or without isoproterenol administration (3 micrograms/h), were subjected to retrograde microcatheterization of the IMCD before and during infusion of 0.83 mol/h KCl. Isoproterenol reduced plasma K concentration and urinary K excretion, but the response to acute KCl infusion was qualitatively similar to control. Isoproterenol decreased delivery of potassium, chloride, and fluid to the IMCD, there was no net transport of K along the duct in either group, and KCl infusion did not result in K secretion in either group. The results indicate that isoproterenol may inhibit K secretion in the late distal or cortical collecting tubule. However, there was no statistically significant difference in K transport along the IMCD between isoproterenol and control groups. Reduced sodium excretion, which was found during isoproterenol administration both before and after KCl infusion, was associated with no change in sodium delivery but with increased sodium reabsorption in the IMCD. This increased sodium reabsorption may be a direct effect of isoproterenol, or may be due to reflex cardiovascular adjustments associated with systemic actions of the drug.

Animals↗

PubMed1991

Kidney function in ANF-transgenic mice: effect of blood volume expansion.

Transgenic mice, created from inbred C3HeB/FeJ embryos, were used to overexpress selectively in the liver a fusion gene comprising mouse transthyretin (TTR) regulatory and atrial natriuretic factor (ANF) structural sequences. Animals were anesthetized, and kidney function was studied before and after blood volume expansion. Baseline urine volumes and electrolyte excretions were not significantly different from those of non-transgenic littermates, despite a markedly lower arterial blood pressure in the experimental group. A slightly lower glomerular filtration rate (GFR) in transgenics was not different statistically. Plasma ANF levels measured by radioimmunoassay were approximately 10-fold higher in the transgenic animals, compared with their nontransgenic siblings. After acute blood volume expansion, the diuretic, natriuretic, kaliuretic, and chloruretic responses were markedly enhanced in the transgenic group. Arterial pressure was increased as a result of hypervolemia, although it remained relatively depressed relative to the controls. GFR again was not different. We conclude that transgenic mice overexpressing ANF can maintain normal excretion of salt and water, possibly via ANF-induced reduction of renal perfusion pressure. After acute blood volume expansion, an increase in pressure may allow full renal expression of the chronically elevated ANF levels.

Animals↗

PubMed1990

Renal regulation of salt balance: a primer for non-purists.

The greater than 40-fold range of voluntary salt intake in humans requires corresponding adjustments in renal excretion to maintain balance. Although many mechanisms have been implicated in the regulation of salt output by the kidney, surprisingly little consideration has been given to their quantitative significance and possible interaction. This survey summarizes the effects of changes in glomerular filtration rate, proximal peritubular physical factors, and plasma concentrations of aldosterone and atrial natriuretic factor (ANF), singly and in combination, on the level of salt excretion. Contrary to expectation, even large increases in filtration or decreases in proximal reabsorption have only minor natriuretic effects, due to constancy of fractional reabsorption in downstream nephron segments. Lack of aldosterone release increases salt excretion as much or more than the upstream mechanisms, whereas ANF-induced inhibition of reabsorption in the medullary collecting duct has the largest effect. It may be concluded, therefore, that the potency of these natriuretic factors increases with distance along the nephron, even though each is operating on a progressively small tubular load. However, none of the mechanisms, in isolation, is sufficient to explain salt balance over the range of voluntary intake. Combination of factors demonstrates synergism rather than simple additivity, resulting in more than enough reserve capacity for salt excretion.

Animals↗

PubMed1990

Nephron site responsible for the reduced kaliuretic response to mineralocorticoids during hypokalemia in rats.

Rats with hypokalemia induced by eating a low-K diet have a diminished kaliuretic response to mineralocorticoids. The purpose of this study was to determine if this was the due to a lower rate of net secretion of K in the cortical collecting duct (CCD) and/or an enhanced rate of reabsorption of K in the medullary collecting duct (MCD). Secondary active secretion of K in the CCD raises the [K] in the lumen as compared to the plasma [TF/P)K). If the (TF/P)K is greater than 1, there was secondary active secretion of K in this nephron segment. The (TF/P)K in the CCD was measured by microcatheterization of the collecting duct. Three groups of rats were studied: rats on a low-K diet with and without the acute administration of DOCA, and rats on a normal-K diet treated with DOCA on a chronic basis. Rats on the low-K diet had a (TF/P)K of 0.8 +/- 0.11; this value did not rise to values significantly greater than 1 after the acute administration of DOCA (1.4 +/- 0.35). In contrast, chronic administration of DOCA to rats fed a normal-K diet did result in a (TF/P)K which was significantly greater than unity (3.1 +/- 0.39). The degree of hypokalemia was not significantly different in these rats. The absolute and fractional reabsorption of K in the MCD was not different in the rats on the low-K diet with or without DOCA. We conclude that the nephron segment which is responsible for the reduced kaliuretic response to mineralocorticoids is the CCD.

Animals↗

PubMed1990

Effects of increased perfusion pressure on medullary collecting duct function.

The role of the medullary collecting duct in pressure natriuresis has not been established. In vivo microcatheterization was used to study the effect of an acute increase in blood pressure induced by bilateral carotid artery and vagal nerve ligation on medullary collecting duct function in anaesthetized rats. Increased fluid and electrolyte excretion during pressure natriuresis were accompanied by increased delivery of water, sodium, chloride, and potassium to the beginning of the medullary collecting duct, a change that was significantly greater than in a second series of time-control animals. These increases in delivery were within the range for which constant fractional NaCl reabsorption had been found previously. However, during increased perfusion pressure, reabsorption of both sodium and chloride in the medullary collecting duct as a fraction of delivered load were reduced from 81 +/- 4.1 to 51 +/- 9.3% (p less than 0.01) and from 65.7 +/- 6.0 to 42.7 +/- 9.1% (p less than 0.01), respectively. No significant changes in medullary collecting reabsorption were seen in the time controls. We conclude that increased perfusion pressure, in addition to increasing delivery to the medullary collecting duct, also inhibits sodium chloride reabsorption in this nephron segment.

Animals↗

PubMed1990

In vivo microperfusion of inner medullary collecting duct in rats: effect of amiloride and ANF.

A method is described that allows perfusion of the inner medullary collecting duct (IMCD) of the rat kidney in situ and in vivo. Fine polyethylene catheters connected to a microperfusion pump were inserted into collecting ducts via the openings at the exposed papilla tip. Perfusate contained 22Na as well as [3H]inulin. During perfusion at 30 nl/min, urine was simultaneously collected. A decrease in the Na-to-inulin concentration ratio in the urinary sample, compared with the perfusate, was taken as indicating unidirectional efflux of Na from the perfused duct system. The effects of luminal amiloride (2 X 10(-4) M) or atrial natriuretic factor (ANF, 10(-8) M) were studied. Compared with control perfusions, both agonists reduced Na efflux from the IMCD to approximately 50%, indicating luminal sites of action. Combination of amiloride and ANF at their respective concentrations had no further effect. The lack of statistically significant additivity suggests, but does not prove, that ANF, administered from the luminal side, is able to block amiloride-sensitive Na channels in the apical membrane of IMCD cells.

Amiloride↗

PubMed1990

Endogenous natriuretic peptides: effect on collecting duct function in rat kidney.

In vivo microcatheterization of the medullary collecting duct of rat kidney was used to compare the functional effects of intravenous infusion of rat atrial natriuretic factor, human urodilatin (a peptide produced in the kidney), or porcine brain natriuretic peptide. All three peptides resulted in striking and quantitatively similar inhibition of NaCl and water reabsorption in the duct. In addition, all three induced significant K+ secretion in this part of the nephron. These results could not be explained by functional alterations in upstream tubular segments. We conclude that the three peptides are equivalent in their transport effects on the inner medullary collecting duct system, when administered at the same (presumably supramaximal) dose.

Animals↗

PubMed1990

Mechanisms of release and renal action of atrial natriuretic factor.

In addition to the well-documented stretch-induced secretion of atrial natriuretic factor (ANF), we have shown that addition of agonists such as vasopressin or angiotensin, added to incubation medium with freshly excised rat atria, caused marked release of the hormone in vitro. Others have had difficulty in reproducing these results. In experiments designed to address this problem we found that removal of the atrial endothelium was necessary to demonstrate agonist-induced release of ANF. The results suggest that the endothelial lining of atrial tissue may limit access of the agonists to the myocytes, and thereby play a modulating role in receptor-stimulated secretion of the hormone. The renal mechanism of action of ANF includes inhibition of Na transport in the medullary collecting duct (MCD). Recent in vitro studies have suggested that this inhibition occurs via blockade of amiloride-sensitive Na channels. However, ANF-induced reduction of MCD transport in vivo is much greater than that obtainable with amiloride. Although, by luminal administration of ANF in vivo, we were able to confirm an amiloride-like action of the hormone at this site, we could not thereby mimic the effects of systemic ANF on MCD Na reabsorption. The results thus indicate that a peritubular effect is an important determinant of ANF natriuresis.

Animals↗