Renal response to ureteral obstruction in early development.
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Animals↗
Biomedical subjects
R L Chevalier
Publications and source records attributed to R L Chevalier.
Selective peripheral dopamine-1 receptor stimulation. Differential responses to sodium loading and depletion in humans.
Dopamine-1 (DA1) receptors in the renal tubules may be involved in the regulation of sodium homeostasis. To test this hypothesis, fenoldopam, a selective DA1 agonist, was infused at 0.05 microgram/kg/min i.v. in 16 normal male subjects in metabolic balance at 300 or 10 meq sodium. Renal function studies were performed by standard p-aminohippurate, inulin, and lithium clearances for three periods: 1) precontrol (2 hours), 2) experimental (3 hours), and 3) postcontrol (2 hours). DA1 receptor stimulation in sodium-loaded individuals increased the following parameters during the experimental period: urine flow rate, from 12.5 +/- 0.4 to 15.5 +/- 0.5 ml/min (p less than 0.05); urinary sodium excretion, from 309 +/- 12 to 489 +/- 18 mu eq/min (p less than 0.001); renal plasma flow, from 631 +/- 19 to 717 +/- 21 ml/min (p less than 0.005); fractional sodium excretion, from 2.2 +/- 0.1% to 3.4 +/- 0.1% (p less than 0.001); fractional lithium excretion, from 26.2 +/- 0.7% to 32.1 +/- 0.8% (p less than 0.005); and distal sodium load, from 10.7 +/- 0.4 to 13.8 +/- 0.5 ml/min (p less than 0.05). The increase in fractional sodium excretion was greater than that of fractional lithium excretion (p less than 0.0001). Distal sodium reabsorption decreased from 78.3 +/- 0.8% to 73.2 +/- 1.1% but the change was not statistically significant. In contrast, sodium-depleted subjects exhibited no significant changes except in renal plasma flow, which rose from 550 +/- 13 to 625 +/- 17 ml/min (p less than 0.0001). Glomerular filtration rate remained unchanged through the entire study. These results indicate that diuretic and natriuretic responses are mediated by DA1 receptors at both proximal and distal tubular sites. Attenuation of the DA1 natriuretic response during sodium depletion suggests a direct inhibition of cellular DA1 mechanisms in the renal tubule or recruitment of nondopaminergic compensatory homeostatic mechanisms within the kidney.
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
Renin release and gene expression in intact rat kidney microvessels and single cells.
To investigate whether newborn kidney microvessels and isolated single microvascular cells have the capacity to release renin and/or alter the expression of the renin gene in response to adenylate cyclase stimulation, newborn kidney microvessels were isolated and purified (95%) using an iron perfusion/enzymatic digestion technique. Incubation of microvessels with either vehicle (control; C) or 10(-5) M forskolin (F) in media resulted in an increase in microvessel cAMP (0.67 +/- 0.13 vs. 22 +/- 4.6 pmol/min per mg protein) (P less than 0.005) and renin released into the culture media (1,026 +/- 98 vs. 1,552 +/- 159 pg angiotensin I/h per mg protein) (P = 0.008) (C vs. F). Renin mRNA levels in the newborn kidney microvessels increased 1.6-fold with forskolin treatment. Renin release by isolated, single microvascular cells (with or without forskolin) was assessed using the reverse hemolytic plaque assay. Forskolin administration resulted in an increase in the number of renin-secreting cells without changes in the amount of renin secreted by individual cells. In conclusion, newborn kidney microvessels and isolated renin-releasing microvascular cells possess a functionally active adenylate cyclase whose short-term stimulation results in accumulation of cAMP, a significant increase in renin release, and an enhancement of renin gene expression. The increase in renin release is due to recruitment of microvascular cells secreting renin. Recruitment of hormone-secreting cells in response to stimuli may prove to be a mechanism of general biological importance shared by many endocrine cell types.
Animals↗
Role of atrial natriuretic peptide in the response to blood volume expansion in the weanling rat.
After acute blood volume expansion (BVE) in the rat, diuresis and natriuresis are reported to be minimal in rats 20 to 30 d of age, but increase to mature levels by 40 d of age. To evaluate the role of atrial natriuretic peptide (ANP) and its renal action in BVE, anesthetized Sprague-Dawley rats were studied at 25 to 30 (group I) and 45 to 50 d of age (group II). Hematocrit, mean arterial pressure, glomerular filtration rate, urine flow rate, urine sodium excretion, urine cyclic GMP excretion, and plasma ANP concentration [( ANP]) were measured before and after infusion of donor littermate whole blood, 2.5% body wt (BVE), and in time controls (no BVE) in each group. Baseline hematocrit, mean arterial pressure, and glomerular filtration rate were greater in group II than group I, but urine flow rate, urine sodium excretion, urine cyclic GMP excretion, and [ANP] did not differ. BVE caused a prompt increase in urine flow rate, urine sodium excretion, and [ANP], but not urine cyclic GMP excretion, in both groups, but there was no difference in the response between groups. Additional groups of rats of the same ages as groups I and II studied using a protocol similar to that of a previous report also showed the "mature" diuretic and natriuretic response even in the younger animals. We conclude that there is no further maturation of the renal response to acute BVE in the euvolemic rat after 25 d of age. The increase in [ANP] after acute BVE in the immature weanling rat is consistent with a role for ANP in mediation of the renal response.
Aging↗
Molecular biology of the renal renin-angiotensin system.
This paper describes an interrelated series of studies designed to examine molecular and cellular aspects of renin expression and release within the kidney. Using immunocytochemical techniques, Northern blot analysis, in situ hybridization, measurement of renin activity, and the reverse hemolytic plaque assay, it has been possible to demonstrate that the intrarenal distribution of renin, renin gene expressing cells and the number of renin secretory cells vary during diverse physiologic and pathologic conditions. Overall, these studies demonstrate that the renal preglomerular vasculature has the plasticity and capacity to elicit a recruitment of renin containing and/or renin gene expressing cells.
Animals↗
Enhanced clearance of vancomycin by hemodialysis in a child.
Clearance of vancomycin by hemodialysis has previously been reported to be negligible. We describe a child undergoing chronic hemodialysis using a hollow fiber dialyzer with cellulose acetate membrane. When the patient was treated with intravenous vancomycin for staphylococcal bacteremia, the serum vancomycin half-life was found to decrease by more than 90% during each course of hemodialysis. We conclude that, contrary to prevailing opinion, vancomycin can be rapidly cleared by hemodialysis in the small pediatric patient, and that the dosage should be adjusted accordingly.
Child↗
The cause of uremia in obstructed kidneys.
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Aging↗
Evidence that intrarenal dopamine acts as a paracrine substance at the renal tubule.
Dopamine is synthesized within the kidney and dopamine 1 (DA1) receptors are associated with the proximal tubule. In pharmacological doses, dopamine increases renal blood flow and sodium excretion. It is possible that dopamine formed intrarenally acts locally via renal dopamine receptors to control renal function. We investigated the possible paracrine action of renal dopamine by intrarenal administration of a specific DA1 antagonist, Sch 23390, in doses confined to the kidney in conscious uninephrectomized dogs (n = 5) in metabolic balance at a sodium intake of 40 meq/day. Changes (mean +/- SE) in renal excretory and hemodynamic function in response to cumulative infusions of several doses of Sch 23390 (0.01, 0.1, 1.0, 5.0, and 10.0 pmol.kg-1.min-1) were studied. Sch 23390 at 0.01 pmol.kg-1.min-1 did not cause any changes in urinary flow rate or sodium excretion. Sch 23390 in doses from 0.1 to 10.0 mol.kg-1.min-1 caused a significant dose-dependent antidiuresis (F = 44.9, P less than 0.0001) and antinatriuresis (F = 42.1, P less than 0.0001) and a decrease in fractional sodium excretion (F = 44.2, P less than 0.0001). No changes in estimated renal plasma flow, glomerular filtration rate, plasma aldosterone concentration, plasma renin activity, or systemic arterial pressure occurred with any dose of intrarenal Sch 23390 infused into the renal artery. Rebound diuresis and natriuresis occurred after cessation of the DA1 blockade.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Distribution of renin mRNA and its protein in the developing kidney.
The intrarenal distribution of renin changes markedly during maturation. To determine whether renin gene expression changes along the developing renal vasculature, renin mRNA distribution was assessed using in situ hybridization histochemistry. Fetal, newborn, and adult kidney tissue sections from Wistar-Kyoto rats were hybridized with an oligonucleotide complementary to rat renin mRNA. In fetal kidneys, renin mRNA was found in the vascular pole of juxtamedullary glomeruli and along afferent, interlobular, and arcuate arteries. In kidneys from newborn rats, renin mRNA localized throughout the whole length of afferent arterioles, but was not detected in interlobular or arcuate arteries. In adult kidneys, hybridization signals were less intense and confined to the juxtaglomerular apparatus. Immunolocalization of renin with a polyclonal anti-rat renin antibody paralleled closely the mRNA distribution. Northern blot analyses demonstrated that renin mRNA levels were higher in fetal and newborn (20- and 10-fold, respectively) than in adult kidneys. We conclude the following. 1) The fetal kidney expresses the renin gene. 2) Expression of the renin gene is subjected to developmental changes. 3) As maturation progresses, localization of renin synthesis and storage shifts from large intrarenal arteries to a restricted, classical juxtaglomerular site in the afferent arteriole.
Animals↗
Obstructive nephropathy in early development.
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Animals↗
Hypercalciuria in the premature infant: influence of diuretic therapy and phosphate depletion.
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Calcium↗
Developmental determinants of recovery after relief of partial ureteral obstruction.
Although obstructive nephropathy is a major cause of renal insufficiency at all ages, the functional consequences of relief of obstruction on the developing kidney are poorly understood. To evaluate recovery from chronic partial ureteral obstruction (CPUO) in the neonatal period, the left ureter of guinea pigs was constricted within the first 48 hours of life, and the obstruction was relieved 10 days later. At three and eight weeks of age, intraureteral pressure, number of perfused glomeruli (NPG), renal blood flow (RBF), and glomerular filtration rate (GFR) were measured. These animals were compared with sham-operated and unrelieved groups. Two additional groups underwent CPUO at five weeks of age, with persistent obstruction or relief in 10 days, and were also studied at eight weeks. In all animals, intraureteral pressure increased during ipsilateral ureteral obstruction and normalized following its release. Recovery of RBF and GFR after relief of ipsilateral CPUO in the newborns was only partial at eight weeks, with no renal growth or increase in NPG from three to eight weeks of age. In contrast, recovery of RBF in the adult was complete 10 days after relief of obstruction, with significant increase in GFR, and no decrease in renal mass or NPG. We conclude that if delayed, relief of CPUO in the neonate may not restore renal growth and functional maturation which have been impaired by CPUO.
Age Factors↗
Intrarenal dopamine acts at the dopamine-1 receptor to control renal function.
Exogenous dopamine increases renal blood flow and produces diuresis and natriuresis in mammalian species. Dopamine is produced intrarenally and dopamine-1 receptors have been demonstrated within the kidney. However, the role of intrarenal dopamine in the control of renal function is unknown. We studied the renal effects of a specific dopamine-1 antagonist, SCH 23390 (SCH, MW 398, Schering-Plough, Bloomfield, New Jersey, USA) infused into the renal artery of uninephrectomized conscious dogs (n = 5) in metabolic balance at a sodium intake of 40 mmol/day. The infusion of SCH at 0.01 pmol/kg per min did not change the urinary flow rate or urinary sodium excretion. Significant dose-dependent reductions in urine volume, urinary sodium excretion and fractional excretion of sodium were observed with intrarenal SCH administration at 0.1, 5.0 and 10 pmol/kg per min. Rebound diuresis and natriuresis occurred after cessation of SCH administration. There were no changes in renal haemodynamic function, systemic plasma renin activity (PRA), plasma aldosterone concentration or mean arterial pressure during intrarenal SCH administration. These results demonstrate for the first time that intrarenal dopamine controls renal function physiologically by acting at the renal dopamine-1 receptors.
Animals↗
Renin and angiotensinogen gene expression in maturing rat kidney.
To determine whether angiotensinogen (Ao) and renin are synthesized by the immature kidney and to assess the changes in intrarenal renin distribution that occur with maturation, the kidneys from 24 newborn and 12 adult Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) were processed for renin immunocytochemistry using a highly specific anti-rat renin antibody. Kidney renin and Ao relative mRNA levels (mRNA/total RNA) were detected by Northern and dot blot techniques, using full-length rat renin and Ao cDNAs. Renal renin concentration (RRC) was measured by radioimmunoassay of angiotensin I (ANG I) and expressed as ng ANG I.h-1.mg protein-1 in the incubation media. RRC was higher in newborn than in adult SHR (979 +/- 164 vs. 206 +/- 47) and WKY (573 +/- 69 vs. 297 +/- 74) (P less than 0.05). In the newborn kidneys of both rat strains, renin was distributed throughout the entire length of the afferent arterioles and interlobular arteries, whereas in the adult kidneys renin was confined to the classical juxtaglomerular position. With maturation, there was a decrease in the proportion of immunoreactive juxtaglomerular apparatuses and arterial segments that contained renin. Kidney renin mRNA levels were 7.9-fold higher in the newborn than in the adult animal. Ao mRNA was detected in the newborn and adult kidneys of both rat strains. This study demonstrates conclusively that both renin and Ao genes are expressed in the newborn kidney, providing evidence for a local renin-angiotensin system that is subjected to developmental changes.
Aging↗
Renin and angiotensinogen gene expression and intrarenal renin distribution during ACE inhibition.
To define whether intrarenal renin and angiotensinogen synthesis and distribution are affected by angiotensin-converting enzyme (ACE) inhibition, a control group of adult, male Wistar-Kyoto rats (n = 7) was compared with a group of rats treated with enalapril (n = 8) for 5 days. Kidney renin and angiotensinogen mRNA levels were detected by Northern and dot blot analysis, using full-length rat renin and angiotensinogen cDNAs. Renin mRNA levels in the enalapril-treated group were 4.6-fold higher than in the control group (P less than 0.05). Angiotensinogen mRNA levels were not significantly different. The intrarenal distribution of renin assessed by immunocytochemistry was markedly different between the two groups of rats. Whereas in the control kidney renin was localized in a juxtaglomerular position, in the kidneys from enalapril-treated rats, renin immunoreactivity of the afferent arteriole extended well beyond the juxtaglomerular loci in the direction of the interlobular artery. The percent of afferent arteriolar length immunostained for renin was higher in the enalapril-treated (53 +/- 17%) than in the control (33 +/- 15) group. Similarly, the ratio of immunostained juxtaglomerular apparatuses (JGA) over total number of JGA and the ratio of immunostained arteries over total number of arteries were higher in the enalapril-treated (0.84 +/- 0.017; 0.68 +/- 0.03) than in the control (0.67 +/- 0.034; 0.43 +/- 0.045) group (P less than 0.05). We conclude that chronic ACE inhibition enhances intrarenal renin synthesis and increases renin expression upstream from the glomerulus and in new sites in blood vessels.(ABSTRACT TRUNCATED AT 250 WORDS)
Angiotensinogen↗
Response of the renin-angiotensin system to relief of neonatal ureteral obstruction.
Chronic partial ureteral obstruction (CPUO) causes an increase in renal vascular resistance (RVR) that can be prevented by angiotensin II (ANG II)-converting enzyme inhibition. To assess the early effects of CPUO, guinea pigs subjected to neonatal left ureteral obstruction were anesthetized at 11-13 days of age for measurement of cardiac output and renal blood flow (RBF) using radioactive microspheres. Although RBF of the hydronephrotic kidney was not decreased at this age, that of the intact kidney more than doubled (P less than 0.01). To evaluate the hemodynamic response to relief of 5 or 10 days of neonatal left CPUO, animals were studied at 19-28 days of age. Although chronic enalapril maleate administration (30 mg.kg-1.day-1) did not further reduce the ratio of RVR to total vascular resistance (TVR) of the postobstructed kidney, it lowered RVR/TVR of the intact contralateral kidney by 40% (P less than 0.05). Renal renin content [RRC, pg angiotensin I (ANG I).mg protein-1.h-1] was twofold higher in both kidneys of animals with unilateral CPUO compared with those of sham-operated guinea pigs (P less than 0.03), and relief of obstruction normalized RRC. The rise in RVR/TVR resulting from ANG II infusion was not different in left kidneys of sham, CPUO, and CPUO-relief groups. However, for the intact kidney of animals with contralateral relief of CPUO, the increase was greater than in remaining groups (P less than 0.05). We conclude that by reducing intrarenal renin, relief of neonatal unilateral CPUO decreased ANG-mediated vasoconstriction of the postobstructed kidney and increased the vasoconstrictor response of the intact kidney to ANG II.
Aging↗
Diuresis and natriuresis during continuous dopamine-1 receptor stimulation.
Stimulation of renal dopamine-1 (DA1) receptors for 3 hours produces an increase in renal plasma flow and sustained natriuresis. The present study was designed to assess the response of renal hemodynamic and tubular function to long-term DA1 receptor stimulation. Fenoldopam, a selective DA1 receptor agonist, was infused intravenously for 24 hours in 10 normal male subjects in metabolic balance at 150 mEq sodium and 60 mEq potassium intake in a single-blind, vehicle-controlled protocol. During DA1 receptor activation, urine flow rate and fractional excretion of sodium increased for the first 5 hours, 16.9 +/- 0.9 ml/min compared with a vehicle control value of 12.4 +/- 0.5 ml/min (p less than 0.001) and 2.0 +/- 0.1% compared with a vehicle control value of 1.1 +/- 0.1% (p less than 0.005), respectively. Urinary sodium excretion rose at 5 hours, 0.27 +/- 0.02 mEq/min compared with a vehicle control value of 0.14 +/- 0.01 mEq/min (p less than 0.01). Renal plasma flow increased during fenoldopam at 5 hours, 505 +/- 47 ml/min compared with a vehicle control value of 397 +/- 25 ml/min (p less than 0.01), and was sustained for 24 hours, 523 +/- 40 ml/min compared with 432 +/- 31 ml/min (p less than 0.05). The distal sodium load increased and the percentage of distal sodium reabsorption decreased during fenoldopam. Glomerular filtration rate, blood pressure, heart rate, plasma aldosterone concentration, plasma renin activity, and fractional excretion of potassium were unchanged. Selective DA1 receptor activation produced sustained 5-hour diuresis and 11-hour natriuresis without kaliuresis or a systemic hemodynamic effect.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Renal effects of atrial natriuretic peptide infusion in young and adult rats.
The immature kidney appears to be less responsive to atrial natriuretic peptide (ANP) than the mature kidney. It has been proposed that this difference accounts for the limited ability of the young animal to excrete a sodium load. To delineate the effects of age on the renal response to exogenous ANP, Sprague-Dawley rats were anesthetized for study at 31-32 days of age, 35-41 days of age, and adulthood. Synthetic rat ANP was infused intravenously for 20 min at increasing doses ranging from 0.1 to 0.8 microgram/kg/min, and mean arterial pressure, glomerular filtration rate, plasma ANP concentration, urine flow rate, and urine sodium excretion were measured at each dose. Since cyclic GMP acts as a second messenger for ANP action, urinary cyclic GMP excretion also was measured. Increasing doses of ANP caused a similar decrease in MAP at all ages studied, and increased glomerular filtration rate in adult but not young rats. Increasing the dose of ANP from 0.1 to 0.4 microgram/kg/min caused a greater rise in urine flow and urinary cyclic GMP excretion in adult than young rats, and urine sodium excretion increased more in adults at all doses (p less than 0.05). However, the rise in plasma ANP concentration also was greater in adults than in young rats (p less than 0.05), indicative of greater systemic clearance of ANP in young animals. Increasing levels of plasma ANP concentration were correlated with a greater rise in urine flow in adult than young (31-32 day old) rats (p less than 0.05), but there was no differential effect on urinary cyclic GMP excretion.(ABSTRACT TRUNCATED AT 250 WORDS)
Aging↗