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Biomedical subjects

R L Chevalier

Publications and source records attributed to R L Chevalier.

At least 19 recordsLinked to original sources

EDRF modulates renal hemodynamics during unilateral ureteral obstruction in the rat.

Unilateral ureteral obstruction (UUO) results in vasoconstriction of the ipsilateral kidney, and vasodilatation of the intact opposite kidney. To investigate the role of endogenous nitric oxide, an endothelial-derived relaxing factor (EDRF), in the regulation of renal hemodynamics during UUO, Sprague-Dawley rats were anesthetized for study 24 hours after left UUO or sham-operation. Total vascular resistance (TVR) and renal vascular resistance (RVR) were measured using radioactive microspheres during control periods and following infusion of the nitric oxide synthase inhibitor, L-NAME (2.5 mg/kg). Blood pressure and RVR were increased by L-NAME, with a greater increment in the RVR/TVR ratio of the kidney with ipsilateral UUO than in the intact opposite kidney or sham-operated kidneys. Infusion of L-arginine (L-Arg), a substrate for nitric oxide synthase, did not alter the RVR/TVR ratio of either kidney of rats with UUO, but reduced the ratio in sham-operated animals. L-NAME tended to reduce urine flow and urinary sodium and cyclic GMP excretion, whereas L-Arg resulted in a marked diuresis, natriuresis, and increased excretion of cyclic GMP in both operative groups. We conclude that EDRF activity is increased in the kidney with ipsilateral UUO, which serves to counteract renal vasoconstriction. This response is not limited by availability of substrate (L-Arg). Vasodilatation of the intact opposite kidney appears to be mediated by factors other than EDRF.

Amino Acid Oxidoreductases

Maturation of cGMP response to ANP by isolated glomeruli.

Experiments were done to determine whether there is a maturational increase in production of guanosine 3',5'-cyclic monophosphate (cGMP) by glomeruli or in eggression of cGMP out of glomerular cells. Both preweaned and adult isolated rat glomeruli responded with an acute rise in intracellular cGMP after 0.5-min exposure to 0.1 microM ANP. However, at 4 h extracellular cGMP was significantly greater in ANP-treated adult compared with preweaned glomeruli (P less than 0.005). In the absence of 3-isobutyl-1-methylxanthine (IBMX) intracellular cGMP was significantly higher in preweaned glomeruli (P less than 0.05). Moreover, the specific activity of phosphodiesterases for cGMP hydrolysis was twofold less in preweaned glomerular membranes (P less than 0.004). Finally, probenecid decreased export of adult glomerular cGMP by 60 +/- 4%, whereas preweaned glomerular cGMP export decreased by only 27 +/- 4% (P less than 0.05). In conclusion, compared with adult, ANP-treated preweaned glomeruli export less cGMP out of glomerular cells, have a higher concentration of intracellular cGMP, and have lower cGMP-specific phosphodiesterase activity, and the organic ion transporter in preweaned glomerular cells exports cGMP less effectively. The limited transport of cGMP out of preweaned glomeruli may account for the blunted natriuretic and diuretic response following ANP stimulation of young rats.

Aging

Localization of cGMP after infusion of ANP or nitroprusside in the maturing rat.

To determine the ontogeny of intrarenal distribution of guanosine 3',5'-cyclic monophosphate (cGMP) formation in response to atrial natriuretic peptide (ANP) or sodium nitroprusside (SNP), adult and neonatal Sprague-Dawley rats were anesthetized and infused for 60 s with rat ANP (5-2,500 micrograms/kg) or SNP (0.1-10.0 mg/kg). cGMP was identified by the immunoperoxidase technique using a specific antibody. In adult rats, infusion of ANP localized cGMP primarily to the glomerular podocytes, whereas stimulation by SNP increased cGMP in the mesangium only (P less than 0.01). In neonatal rats, although overall renal cGMP immunostaining was greater than in adults, specific localization to podocytes (ANP) or mesangium (SNP) resulted only with higher doses of agonists. Although basal generation of cGMP by isolated glomeruli was greater in neonatal rats, the threshold for stimulation by ANP was lower in glomeruli from adult rats. We conclude that in vivo ANP stimulates glomerular particulate guanylate cyclase primarily in the podocytes, whereas SNP stimulates soluble guanylate cyclase localized to the mesangial cells. There is a maturational increase in the sensitivity for activation of glomerular particulate and soluble guanylate cyclase.

Aging

Distribution and content of renin and renin mRNA in remnant kidney of adult rat.

To determine whether kidney hypertrophy secondary to reduction of renal mass affects the intrarenal distribution and concentration of renin mRNA and its protein, adult male Sprague-Dawley rats were studied 4 wk after sham operation (Sham, n = 10), uninephrectomy (UNX, n = 14), or five-sixths nephrectomy (5/6 NX, n = 12). Left kidney weight-to-body weight ratio (x10(3)) was higher in 5/6 NX (6.6 +/- 0.2) than in UNX (4.5 +/- 0.2) or Sham (3.8 +/- 0.1) groups (P < 0.001). The percentage of juxtaglomerular apparatuses (%JGA) containing renin was lower in 5/6 NX (32 +/- 5) than in UNX (56 +/- 2, P < 0.001) or Sham (50 +/- 1, P < 0.05) groups. Renal renin mRNA concentrations (pg renin mRNA/microgram total RNA) detected by radiodensitometric renin mRNA dot-blot assay were lower in 5/6 NX (1.8 +/- 0.3) than in UNX (13.2 +/- 1) or Sham (14.2 +/- 1.1, P < 0.001). In situ hybridization histochemistry demonstrated that in all groups of rats renin mRNA was confined to the JGA. However, the hybridization signals (grains/JGA) were less intense in 5/6 NX (211 +/- 24) than in UNX (486 +/- 35) or Sham (541 +/- 40) groups (P < 0.001). Renal renin concentration (ng angiotensin I.mg protein-1.h-1) tended to be lower in 5/6 NX (20 +/- 15) than in UNX (44 +/- 7.8) or Sham (60.8 +/- 10) groups. In addition, plasma renin activity (ng.ml-1.h-1) was lower in 5/6 NX (3.8 +/- 0.6) than in UNX (8.8 +/- 1.8, P < 0.05) or Sham (14.3 +/- 2, P < 0.001) groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Inhibition of ANP clearance receptors and endopeptidase 24.11 in maturing rats.

Systemic clearance of atrial natriuretic peptide (ANP) decreases during postnatal development. To determine the relative contribution of ANP clearance (C) receptors and neutral endopeptidase 24.11 (NEP; EC 3.4.24.11) in regulation of plasma ANP concentration ([ANP]) during maturation, 18- to 60-day-old male Sprague-Dawley rats were anesthetized and infused with rat ANP (35 ng.kg-1.min-1). Infusion of the NEP inhibitor phosphoramidon increased [ANP] and urine guanosine 3',5'-cyclic monophosphate (cGMP) excretion in both weanling and adult rats. Infusion of C-ANP, an analogue that binds C receptors selectively, resulted in a greater rise in [ANP] in preweaned than in adult rats, suggesting a maturational decrease in function of C receptors. Despite the increase in [ANP], however, urine flow, cGMP, and sodium excretion failed to increase in preweaned compared with adult rats. Combined infusion of phosphoramidon and C-ANP resulted in a marked increase in [ANP] and cGMP excretion in weanling and adult rats. These results indicate that both C receptors and NEP modulate plasma [ANP] in the physiological range and that each pathway compensates when the other is inhibited. Age-related differences in the renal response to ANP clearance inhibitors may have important physiological implications in the regulation of sodium balance during development.

Animals

Renal nerves modulate renin gene expression in the developing rat kidney with ureteral obstruction.

Chronic unilateral ureteral obstruction (UUO) in newborn rats activates renin gene expression in the obstructed kidney, and increases renin distribution along afferent glomerular arterioles in both kidneys. To investigate the role of the renal nerves in this response, 2-d-old Sprague-Dawley rats were subjected to UUO or sham operation. Chemical sympathectomy was performed by injection of guanethidine, whereas, control groups received saline vehicle. At 4-5 wk, renal renin distribution was determined by immunocytochemistry, and renin mRNA levels were determined by Northern blot hybridization. Compared to the saline-treated rats with UUO, renin remained localized to the juxtaglomerular region in both kidneys of rats with UUO receiving guanethidine (P less than 0.05). Moreover, renin mRNA levels were eightfold lower in obstructed kidneys of rats receiving guanethidine than in those receiving saline. Additional groups of rats with UUO were subjected to unilateral mechanical renal denervation: renin gene expression in the obstructed kidney was suppressed by ipsilateral but not by contralateral renal denervation. These findings indicate that either chemical or mechanical denervation suppressed the increase in renin gene expression of the neonatal kidney with ipsilateral UUO. We conclude that the renal sympathetic nerves modulate renin gene expression in the developing kidney with chronic UUO.

Animals

Hepatic angiotensinogen gene regulation in the fetal and pregnant rat.

To determine whether expression of the hepatic angiotensinogen (Ao) gene is modulated by 1) ontogeny, 2) pregnancy, 3) glucocorticoids, or 4) triiodothyroxine (T3), time-dated pregnant Wistar-Kyoto rats were studied at different gestational ages (15, 17, and 20 d) without the influence of hormonal treatment or were given a daily intraperitoneal injection of dexamethasone (Dex) or T3 for 5 d (chronic Dex or T3) or a single injection of Dex (acute Dex). Maternal and fetal hepatic Ao mRNA levels were detected by dot and Northern blot analysis by using a full-length rat Ao cDNA. Fetal Ao mRNA levels were lower than in their maternal counterparts and lower than in adult rats of either sex. Maternal hepatic Ao mRNA levels were markedly diminished. mRNA levels were their lowest at 15 d of gestation and increased progressively as gestation advanced, reaching a peak at 20 d of gestation. Chronic Dex treatment resulted in a 190% increase in maternal and a 370% increase in the fetal hepatic Ao mRNA levels. Acute Dex treatment resulted in a 260% increase in maternal hepatic Ao mRNA levels with no change in the fetus. Hepatic Ao mRNA levels increased to the nonpregnant level with acute and chronic Dex treatment. Chronic T3 treatment resulted in a 20% increase in maternal hepatic Ao mRNA levels, without alteration of fetal Ao gene expression. We conclude that 1) the fetal and pregnant state results in a profound decrease in maternal and fetal hepatic Ao gene expression, 2) Ao gene expression is regulated by glucocorticoids in the term fetal and maternal liver, and 3) chronic T3 treatment results in a modest increase in maternal hepatic Ao gene expression.

Angiotensinogen

Acute torsion of a renal transplant: cause of organ loss.

Acute torsion of a renal allograft has not been previously described as a cause of organ loss. We present a case of acute torsion of a transplanted kidney in a patient with prune-belly syndrome which led to renal necrosis, necessitating organ removal.

Humans

Counterbalance in functional adaptation to ureteral obstruction during development.

Renal counterbalance, as described by Hinman in 1923, is the phenomenon of increased function of the intact kidney in proportion to the loss of function resulting from unilateral ureteral obstruction (UUO). In the neonatal guinea pig, chronic partial UUO results in severe vasoconstriction and growth arrest of the ipsilateral kidney. Angiotensin II appears to contribute significantly to the vasoconstriction, and the renin-angiotensin system is also involved in the hemodynamic response of the intact opposite kidney to UUO and to relief of UUO. Immunolocalization of renin following complete UUO in the neonatal rat revealed extension of renin-containing cells along the length of the afferent arteriole in both the obstructed and the intact opposite kidney. The proportion of juxtaglomerular apparatuses with detectable renin and renin messenger ribonucleic acid (mRNA) (identified by in situ hybridization), as well as renal renin content (a measure of active renin), were increased in the obstructed kidney compared with the intact opposite kidney. Chemical sympathectomy by chronic guanethidine administration reduced the total renin mRNA in the obstructed kidney (determined by Northern blot analysis) and prevented the increased renin immunostaining in both kidneys. Thus, renal counterbalance in the developing kidney subjected to UUO is mediated or modulated by the renal nerves and involves marked alterations in gene expression and cellular processing of renin.

Humans

Interrelationship of atrial natriuretic peptide, atrial volume, and renal function in premature infants.

Infants experience dramatic changes in fluid balance during the first few days of life, which provides an opportunity to observe the interrelationships of changing atrial size, atrial natriuretic peptide (ANP) secretion, and renal function during a relatively short period. To study these relationships, we examined nine infant boys (mean birth weight 1180 gm and gestational age 30 weeks) at 20 to 28 hours of age and then at four 24-hour intervals. Measurements included plasma ANP concentration, two-dimensional echocardiographic estimations of left and right atrial volumes, Doppler determination of ductus arteriosus patency, creatinine clearance, urine flow rate, urinary sodium excretion, and cyclic guanosine monophosphate (cGMP) excretion. Plasma ANP concentration was found to decrease with age and to correlate with decreasing size of the right atrium, closure of the ductus arteriosus, urinary cGMP excretion, and sodium excretion. We speculate that elevated plasma ANP values in a preterm neonate reflect an expanded volume state. As volume contraction, reflected by decreasing atrial volume and body weight occurs, ANP levels decrease, which may diminish diuresis. These findings are compatible with a significant role for ANP in volume homeostasis of newborn infants.

Atrial Natriuretic Factor

Special needs of the newborn infant in fluid therapy.

The preterm baby, although less able to tolerate high fluid and solute loads, has a remarkable ability to adapt to a rather broad range of environmental challenges, and thus renal function in the preterm infant should no longer be considered impaired. Lower rather than higher fluid administration is the current trend in neonatal care because it is safer and more physiologic. Although changes in body weight over time provide a good indicator of water balance, determination of plasma and urine electrolytes and tonicity are also essential in the monitoring of fluid therapy in preterm infants.

Body Water

Expression of renin and its mRNA in the adult rat kidney with chronic ureteral obstruction.

Angiotensin II has been implicated in mediating renal vasoconstriction resulting from chronic unilateral ureteral obstruction (UUO) in both mature and developing animals. We have previously shown that chronic neonatal UUO results in increased distribution of renin and its mRNA in the obstructed kidney, as well as of immunoreactive renin in the intact opposite kidney. The present study was designed to evaluate the effects of 24 hours versus 4 weeks of UUO on the distribution of renin mRNA and its protein in the adult rat kidney. Renin was detected by immunocytochemistry using a polyclonal anti-rat renin antibody. Renin mRNA was localized by in situ hybridization to an oligonucleotide complementary to renin mRNA. UUO of 24 hours' or 4 weeks' duration did not alter the distribution of renin and its mRNA in the obstructed kidneys as compared with sham-operated kidneys, although kidneys obstructed for 4 weeks had a significant increase in the percent of renin-containing juxtaglomerular apparatuses (JCA) when compared with the intact opposite kidneys (P less than 0.05). Compensatory hypertrophy was not present in the intact opposite kidneys after 24 hours of UUO and distribution of renin gene expression was not altered at that time. However, 4 weeks following contralateral UUO, the intact kidneys were hypertrophied and showed a decrease in renin gene expression relative to the obstructed and sham-operated kidneys. We conclude that unlike UUO during early development, chronic UUO in the mature animal does not activate renin gene expression nor alter renin distribution in the obstructed kidneys. Renin gene expression is suppressed in the hypertrophied kidney with prolonged contralateral UUO.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Dopamine-1 and dopamine-2 mechanisms in the control of renal function.

Dopamine (DA), a catecholamine produced in the kidney, is a renal vasodilator and natriuretic substance, but its action at dopamine-1 (DA-1), dopamine-2 (DA-2) and alpha- and beta-adrenergic receptors limits its effectiveness as a heuristic tool and pharmacologic agent. We have studied the effects of highly selective DA-1 and DA-2 receptor agonists and antagonists in normal human subjects and experimental animals to determine the precise physiological role of renal dopamine at DA-1 and DA-2 receptors within the kidney. We studied fenoldopam, a selective DA-1 agonist, in normal human subjects in metabolic balances at high (300 mEq/day) and low (10 mEq/day) sodium (Na) intake. Selective DA-1 receptor stimulation during high Na intake resulted in renal vasodilation, natriuresis and diuresis in a sustained manner for 3 hours. The natriuresis was mediated by a reduction in Na reabsorption at both proximal and distal tubular sites. In contrast, during low Na intake, DA-1 receptor stimulation did not engender a natriuretic or diuretic response. Thus, sodium depletion may inhibit the function of renal tubular cells in response to DA-1 stimulation. DA-1 receptors are present in the medial layer of the renal vasculature, proximal tubule and cortical collecting duct; DA-2 receptors are localized to the glomerulus, the renal nerves surrounding renal blood vessels and possibly the renal vascular endothelium. We have performed studies in conscious dogs with indwelling renal arterial catheters to identify the physiological role of renal DA to DA-1 and DA-2 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben

Hematocrit modulates response of ANP to volume expansion in immature rats.

Compared with the adult, the immature kidney responds to acute volume expansion (VE) with reduced diuresis and natriuresis. The underlying mechanisms are poorly understood. Diuresis and natriuresis are blunted despite a lower hematocrit (Hct) in the immature rat, which should enhance the response to VE. The present study was designed to evaluate the role of atrial natriuretic peptide (ANP), its second messenger, guanosine 3',5'-cyclic monophosphate (cGMP), and Hct in the regulation of the renal response to acute saline VE (3% body wt) during postnatal development in rats. Anesthetized Sprague-Dawley rats were studied in the preweaning (group P) or postweaning period (group W). In additional groups, Hct was increased in preweaned rats (group PI) and decreased in postweaned rats (group WD) by isovolemic exchange transfusion before VE. Although control plasma ANP concentration [( ANP]) was not different among the four groups, the increased diuretic and natriuretic response to VE in group W was associated with a greater increase in [ANP] and urinary cGMP excretion (UcGMPV) than in group P (P less than 0.05). Experimental increases in Hct in group PI resulted in greater [ANP] after VE but a reduction in UcGMPV and diuresis (P less than 0.05), whereas decrease in Hct in group WD increased UcGMPV without a significant effect on [ANP], diuresis, or natriuresis. We conclude that ANP may contribute to the increasing renal response to VE with maturation and that Hct modulates ANP release, UcGMPV, and the renal response to VE in postnatal maturation.

Aging