Biomedical subjects

R L Chevalier

Publications and source records attributed to R L Chevalier.

At least 55 records · Page 3Linked to original sources

PubMed1996

Renal apoptosis and clusterin following ureteral obstruction: the role of maturation.

PURPOSE: Unilateral ureteral obstruction (UUO) increases renal apoptosis as well as clusterin, which in turn is modulated by angiotensin II. The present study was designed to investigate the role of maturation in these responses. MATERIALS AND METHODS: Neonatal and adult Sprague-Dawley rats underwent UUO or sham operation. Fourteen days later, renal apoptosis was quantitated by flow cytometry, and renal messenger RNA (mRNA) was quantitated for renin and clusterin. Apoptotic cells, macrophages, clusterin and Dolichos biflorus agglutinin were localized by immunohistochemistry. RESULTS: Following ipsilateral UUO, renal DNA content increased in the adult but decreased in the neonate. Renal macrophage infiltration induced by UUO was 2-fold greater in adults than in neonates, while distal tubular apoptosis was 2-fold greater in neonatal than in adult kidneys. Unilateral ureteral obstruction markedly increased renal renin mRNA expression in the neonate, but not in the adult, while clusterin expression was greater in adults than in neonates. Clusterin was localized to some, but not all, distal tubules containing apoptotic cells. CONCLUSIONS: We conclude that, compared with the adult, UUO in the neonate induces greater apoptosis, which in turn contributes to reduced renal DNA. This may be modulated by relative suppression of clusterin in the obstructed neonatal kidney due to greater activation of the renin-angiotensin system.

Aging↗

PubMed1995

Ureteral obstruction in the neonatal guinea pig: interaction of sympathetic nerves and angiotensin.

The contribution of sympathetic nerves to the hemodynamic effects of unilateral ureteral obstruction (UUO) was investigated in the neonatal guinea pig. The left ureter was partially constricted (or sham-operated) at birth, and sympathetic innervation was inhibited by guanethidine and compared with saline vehicle-treated animals. At 15-20 days of age, blood pressure, cardiac output, total vascular resistance (TVR), renal blood flow, and renal vascular resistance (RVR) were determined before and after infusion of enalapril. UUO reduced cardiac output, increased TVR, and increased RVR of the ipsilateral kidney, whereas guanethidine treatment had no additional effects. Enalapril decreased RVR only in obstructed kidneys and not in intact opposite kidneys of animals with UUO. This was not affected by guanethidine administration. In contrast, enalapril decreased RVR only in guanethidine-treated (but not saline-treated) sham-operated guinea pigs. Therefore, UUO increases angiotensin-dependent vascular tone of the ipsilateral kidney independent of renal innervation. However, UUO decreases angiotensin-mediated vascular tone of the contralateral kidney, an effect unmasked by sympathectomy.

Angiotensin II↗

PubMed1995

Ureteral obstruction in the neonatal rat: renal nerves modulate hemodynamic effects.

In the neonate, chronic unilateral ureteral obstruction (UUO) reduces renal blood flow (RBF) of the ipsilateral kidney and increases RBF of the opposite kidney. To determine whether renal nerves mediate or modulate these responses, complete left UUO in the neonatal rat was used as a model of severe obstructive uropathy, and was compared with sham-operated controls. At 24-28 days of age, animals underwent left or right mechanical renal denervation or left sham renal denervation. One week after denervation, animals were anesthetized and blood pressure and heart rate were measured. Cardiac output and RBF were determined by the radioactive microsphere technique. UUO increased blood pressure and heart rate, and decreased RBF in the obstructed kidney, regardless of denervation. While left UUO increased RBF to the intact opposite kidney in rats with left renal denervation, this was attenuated by right renal denervation. Thus, in the neonatal rat, UUO modulates systemic renal hemodynamics, possibly through activation of the renin-angiotensin system. While renal nerves do not mediate the vasoconstriction of the obstructed kidney, renal nerves modulate vascular tone of the kidney contralateral to UUO.

Animals↗

PubMed1995

Chronic sodium loading augments natriuretic response to acute volume expansion in the preweaned rat.

Positive sodium balance is necessary for normal somatic growth of the neonate, and the neonatal renal response to volume expansion (VE) is attenuated compared with the adult. To test the hypothesis that dietary sodium modulates the developmental response to VE, preweaned rats were artificially reared with either a normal (25 meq/l)- or high-sodium (145 meq/l) diet for 7-8 days and were compared with adult rats receiving normal or high sodium. Serum sodium concentration remained normal in adults on high sodium, whereas neonates became hypernatremic. Glomerular filtration rate (GFR), urinary flow (V), and urinary sodium (UNaV) were measured before and after acute saline VE (1% body wt). While remaining constant in preweaned rats, GFR increased > 50% in adult rats after VE (P < 0.05). High sodium intake augmented V and UNaV after VE but was not sustained in neonates as in adults. Plasma atrial natriuretic peptide (ANP) and guanosine 3',5'-cyclic monophosphate excretion (UcGMPV) were measured, and baseline UcGMPV was lower in preweaned rats receiving normal sodium but increased to levels similar to adult levels after VE. Postexpansion plasma ANP was higher in preweaned rats than in adult rats and was not affected by dietary sodium regardless of age. We conclude that the attenuated postexpansion natriuresis in the neonate is due in part to an adaptive response to limited sodium intake. However, neonatal compensation to increased sodium intake is incomplete and independent of plasma ANP.

Aging↗

PubMed1995

Regulation of renal growth factors and clusterin by AT1 receptors during neonatal ureteral obstruction.

Unilateral ureteral obstruction (UUO) in the neonate impairs growth of the ipsilateral kidney. Since renal renin expression is increased by UUO, we hypothesized that, by activation of AT1 receptors, angiotensin II (ANG II) regulates expression of transforming growth factor-beta 1 (TGF-beta 1) and epidermal growth factor (EGF) in the obstructed kidney. Sprague-Dawley rats underwent left UUO or sham operation within the first 48 h of life and received losartan, 40 mg.kg-1.day-1, or saline. After 14 days, steady-state renal mRNA was determined for renin, TGF-beta 1, EGF, and clusterin. Losartan reduced the DNA content of the intact kidneys but did not further decrease that of the obstructed kidney. Losartan increased renal renin expression and decreased EGF expression by 80%, regardless of UUO. In contrast, losartan reduced TGF-beta 1 expression by 34% in obstructed kidneys but did not affect TGF-beta 1 in intact kidneys. Losartan increased clusterin expression by 60% in obstructed kidneys and seven-fold in intact kidneys. We conclude that activation of the ANG II AT1 receptor is necessary for normal renal growth and that TGF-beta 1 is regulated by AT1 receptors in the obstructed, but not intact, kidneys. Through AT1 receptors, endogenous ANG II stimulates EGF and inhibits clusterin expression.

Angiotensin II↗

PubMed1995

Dietary sodium modulates neonatal but not adult cardiac atrial natriuretic peptide in rats.

After an initial postnatal diuresis, neonates are in positive sodium balance. Because atrial natriuretic peptide (ANP) contributes to sodium homeostasis, this study was designed to evaluate the maturational effects of increased dietary sodium intake on cardiac ANP production. Preweaned Sprague-Dawley rat pups were artificially reared by feeding them either a normal-sodium or high-sodium diet for 7 d and were compared with maternally reared rat pups. Adult rats were divided into three groups: the first group was given ad libitum rat food and 1% sodium chloride to drink, the second group was pair-fed with this group but given tap water to drink, and the third group was fed ad libitum rat food and water for 10 d. Atrial and ventricular pro-ANP and ANP contents and plasma ANP concentrations were measured by RIA. Steady state atrial and ventricular ANP mRNA expression was determined by Northern and dot-blot analysis. There was a 2-fold increase in atrial pro-ANP and ANP content and a 50% decrease in plasma ANP concentration in preweaned rat pups fed a high-salt diet. In contrast, atrial pro-ANP and ANP content and plasma ANP concentration were not affected by increased sodium intake in adult rats. Atrial and ventricular ANP mRNA levels and ventricular pro-ANP and ANP contents were not altered by dietary sodium at either age. We conclude that chronic increase in sodium intake in the preweaning period results in increased storage of atrial pro-ANP. The decrease in plasma ANP concentration in these preweaned rats may be due to reduced basal secretion or enhanced degradation of the peptide.

Animals↗

PubMed1995

Unilateral ureteral obstruction increases glomerular soluble guanylyl cyclase activity.

RBF and GFR are decreased in kidneys after ipsilateral unilateral ureteral obstruction (UUO) for 24 h. Despite net vasoconstriction, vasodilatory mechanisms respond to counterbalance the vasoconstriction: the inhibition of nitric oxide synthase activity is associated with a greater reduction in RBF with ipsilateral UUO. To determine whether the stimulation of soluble guanylyl cyclase differs between glomeruli from obstructed kidneys and normal kidneys, cGMP was measured after stimulation by 10(-3) M sodium nitroprusside (SNP) in glomeruli isolated from the kidneys of Sprague-Dawley rats after 24 h of UUO or sham operation. The generation of intracellular and extracellular (EC) cGMP (femtomoles of cGMP/100 glomeruli/per hour) was measured by RIA. After incubation with SNP, the EC accumulation of cGMP by UUO glomeruli was significantly greater than that by glomeruli from sham-operated rats (P < 0.05). When glomerular studies were repeated in the presence of the phosphodiesterase inhibitor isobutyl methylxanthine, there was no difference in the EC accumulation of cGMP. The direct measurement of cGMP hydrolysis by phosphodiesterase was significantly less in glomerular homogenate from UUO rats compared with sham-operated rats (P < 0.05). When 10(-5) M losartan, an angiotensin II receptor inhibitor, was included in glomerular incubations, there was a significant decrease in the EC glomerular cGMP response to SNP in UUO glomeruli (P < 0.05). This attenuated response was abolished by the addition of isobutyl methylxanthine. The addition of angiotensin II did not alter the accumulation of cGMP by UUO or sham glomeruli. These studies indicate that decreased phosphodiesterase activity in UUO glomeruli contributes to the enhanced accumulation of EC glomerular cGMP after the stimulation of soluble guanylyl cyclase by SNP. In addition, angiotensin II receptors modulate this response, suggesting a role for soluble guanylyl cyclase in countering angiotensin-mediated vasoconstriction due to UUO.

Angiotensin II↗

PubMed1995

Effects of ureteral obstruction on renal growth.

Renal insufficiency due to congenital obstructive nephropathy is a consequence of arrested or abnormal renal growth. A number of experimental studies have shown that the younger the age at the time of unilateral ureteral obstruction (UUO), the more severe the growth impairment of the ipsilateral kidney, and the greater the compensatory growth of the opposite kidney ("counterbalance"). Urinary obstruction in early fetal life results in renal dysplasia and a decrease in the number of functioning nephrons. The renin-angiotensin system is highly activated in early development, and UUO further increases this activity, resulting in vasoconstriction and glomerular contraction. Long-term UUO also causes progressive interstitial fibrosis, which presumably contributes to arrested growth of the kidney. This may result from excessive deposition of extracellular matrix stimulated by increased expression of transforming growth factor-beta 1. Neonatal UUO delays the expression of epidermal growth factor, and prolongs the expression of peritubular alpha smooth muscle actin, suggesting that renal maturation is delayed by UUO. Renal apoptosis is increased by UUO, which may contribute to the reduced DNA content of the neonatal obstructed kidney. Renal expression of clusterin, a glycoprotein associated with cell adhesion and protection from apoptosis, is increased by ipsilateral UUO, and also presumably modulates renal growth. Thus, renal growth and development are impaired by UUO through complex interactions between regulators of cell proliferation, cell destruction, and extracellular matrix.

Aging↗

PubMed1994

Neonatal ureteral obstruction stimulates recruitment of renin-secreting renal cortical cells.

Unilateral ureteral obstruction (UUO) in the neonate increases ipsilateral renal renin gene expression, an effect which is mediated by renal nerves. To determine whether neonatal UUO alters the number of renal cortical cells secreting renin and whether this change is modulated by renal nerve activity, newborn Sprague-Dawley rats were subjected to left UUO, right uninephrectomy, or sham operation and studied four weeks thereafter. To evaluate the importance of renal nerves in this response, an additional group of animals underwent chemical sympathectomy with guanethidine. Ureteral obstruction was associated with marked reduction in renal mass in the obstructed kidney and contralateral compensatory hypertrophy, changes which were not altered by sympathectomy. Renin messenger RNA and renal renin content were elevated in the obstructed kidney. The number of cells secreting renin, measured by the reverse hemolytic plaque assay, was markedly increased in the obstructed kidney (45 +/- 18 plaques/slide vs. 11 +/- 1 plaques/slide in sham animals), but not in the opposite kidney or following uninephrectomy. This effect was not significantly altered by sympathectomy. There was no change in the amount of renin secreted per cell or in the secretory response to Ca++. These results show that UUO results in recruitment of cells not previously secreting renin by a mechanism independent of renal nerve activity. This recruitment occurs without alteration of the quantity of renin secreted per cell or in the normal regulatory effect of Ca++ on renin secretion. An increase in the number of renin-secreting cells may contribute to the activation of the renin-angiotensin system, and thus to the vasoconstriction observed following ureteral obstruction.

Animals↗

PubMed1994

Neonatal renal function and physiology.

Birth rapidly changes the demands placed on the kidneys with respect to infant homeostasis. Conceptional age (gestational plus postnatal), general health, and medical management may independently, or, in concert, give rise to important metabolic abnormalities marked by apparent renal functional inadequacies. The chronology of the renal functional changes occurring with maturation in infants born before or at term is now well described. The confounding effects of treatment on the development of renal function in very low birth weight infants are also becoming more apparent. However, the mechanisms responsible for these changes are just becoming to be understood with the use of molecular biologic techniques.

Age Factors↗

PubMed1994

Angiotensin II type 1 receptor: role in renal growth and gene expression during normal development.

To determine whether angiotensin II (ANG II) modulates renal growth and renin and angiotensin type 1 (AT1) gene expression via AT1 during development, weanling rats were given ANG II antagonist losartan (DuP 753) for 3 wk. Body weight (g), kidney weight (g), and kidney weight-to-body weight ratio were lower in losartan-treated rats (162 +/- 7, 1.6 +/- 0.06, and 9.5 +/- 0.1 x 10(-3)) than in control rats (184 +/- 5, 1.8 +/- 0.07, and 10.1 +/- 0.1 x 10(-3); P < 0.05). Renal DNA content (mg/kidney) was lower in losartan-treated (2.4 +/- 0.17) than in control rats (3.3 +/- 0.31; P < 0.05), whereas protein-to-DNA and RNA-to-DNA ratios were similar in losartan-treated and control rats. Renin mRNA levels were sevenfold higher in losartan-treated than in control rats, as determined by quantitative standardized dot blot analysis. In addition, blockade of AT1 with losartan induced recruitment of renin-synthesizing and renin-containing cells in the renal vasculature, as determined by immunocytochemistry and in situ hybridization. To establish whether AT1 blockade has a direct effect on renin gene expression, freshly isolated renin-producing cells were exposed in vitro to losartan (10(-6) M) or culture media (control). Losartan induced a twofold increase in steady-state renin mRNA levels above control (P < 0.05). Intrarenal AT1 mRNA levels were not altered by losartan given either in vivo or in vitro to freshly dispersed cells. To define whether immature renin-secreting cells are responsive to ANG II, renin release was determined by reverse hemolytic plaque assay.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1994

Kidney and urologic disorders in the age of enlightenment.

The Enlightenment, a unique period in the history of Europe, was founded in the scientific and intellectual revolution of the 17th century. Renal anatomy and physiology advanced through the work of men like Eustachio, Malpighi, von Rosenstein and Cotugno, who described both normal and pathologic structures. Despite the earlier discovery of renal tubules and glomeruli, their anatomic and physiologic relationship remained unclear during the 18th century. The definitive explanation would not come until the work of Bowman and Bright in the 19th century. Similarly, the role of renal nerves would not emerge until the 19th century, when Claude Bernard elucidated their role in controlling urine flow in the dog. A key figure was Morgagni (1682-1771), who provided highly precise descriptions of a number of urinary tract anomalies and forms of obstructive nephropathy and developed many insights into renal pathophysiology by pure deductive reasoning. He gave a remarkably accurate description of the basis of reflux nephropathy and recognized that urinary calculi could have many etiologies. Lithotomy was performed as a last resort, and Cheselden reduced the mortality to 17% with a perineal approach; Baseilhac designed a new instrument to facilitate the suprapubic approach. Despite the high quality of men such as Morgagni, physicians had a reputation for quackery and rapacity, and most of their efforts met with little success.

Europe↗

PubMed1994

Maturation of A71915-dependent inhibition of atrial natriuretic peptide-stimulated cyclic GMP production in isolated rat glomeruli.

Atrial natriuretic peptide (ANP) regulates glomerular hemodynamics by interaction with biologic receptors (GC-A/ANP) that possess particulate guanylyl cyclase activity. In a previous study we have shown a developmental difference in glomerular response to ANP where preweaned glomeruli produced significantly less extracellular cGMP in response to ANP. Because of the possibility that functional differences in the ANP biologic receptor might exist during development, further characterization of GC-A/ANP receptor response in glomeruli of developing rats was done using a structural analogue of ANP. A71915 (Abbott Laboratories) is a structural analogue of ANP which has been shown to inhibit activation of ANP receptor-associated guanylyl cyclase in vascular smooth muscle cells. The purpose of this study was to investigate the ability of A71915 to inhibit ANP-stimulated cGMP response in isolated glomeruli of adult and preweaned rats. Isolated glomeruli from preweaned or adult rat kidneys were preincubated for 15 min with A71915 (10(-5) M) prior to addition of ANP (up to 10(-6) M). Glomerular response of production of intracellular and extracellular cGMP was measured by radioimmunoassay. Adult glomeruli produced significantly greater amounts of extracellular cGMP compared to preweaned glomeruli for concentrations of ANP > or = 10(-9) M. Infant glomeruli had a significant decrease in the production of ANP-stimulated intracellular cGMP in the presence of A71915 (10(-5) M), whereas extracellular cGMP production was unchanged. In contrast both ANP-stimulated intracellular and extracellular cGMP were significantly decreased by A71915 in adult glomeruli. These results demonstrate the maturation of the glomerular response to ANP.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

PubMed1993

Atrial natriuretic peptide in renal development.

Although discovered little more than a decade ago, atrial natriuretic peptide (ANP) has been shown to play a significant role in the maintenance of sodium homeostasis. Immediately after birth, plasma ANP concentration is very high concurrent with right atrial dilatation and a high urinary excretion of cyclic GMP (cGMP), the second messenger for ANP. Following postnatal diuresis and natriuresis, atrial volume, plasma ANP concentration, and urinary cGMP excretion decrease to baseline levels. In the ensuing suckling period, the diuretic and natriuretic response to acute saline volume expansion are attenuated, an effect which is offset by the lower hematocrit at this age. Increase in hematocrit by isovolemic exchange transfusion results in a greater rise of plasma ANP concentration following volume expansion, but a reduced excretion of cGMP. Intravenous infusion of ANP results in greater plasma ANP concentration, and greater urinary excretion of cGMP and sodium, in adult than in young rats. This increased metabolic clearance of ANP during early development is due at least in part to increased activity of clearance receptors. In addition, neutral endopeptidase contributes to removal of circulating ANP in maturing as well as adult rats. Infusion of ANP in neonatal or adult rats results in accumulation of cGMP in glomerular podocytes, with a higher threshold for activation in immature animals. Despite the similar response of intracellular generation of cGMP following exposure to ANP in neonatal and adult rats, egression of ANP out of glomeruli is low in neonates, an effect that is due to immaturity of an organic acid transporter.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

PubMed1993

Decreased perfusion pressure modulates renin and ANG II type 1 receptor gene expression in the rat kidney.

To determine whether decreased perfusion pressure affects the abundance and distribution of renin and its mRNA and the expression of the angiotensin II type 1 (AT1) receptor gene within the kidney, adult male Sprague-Dawley rats were subjected to aortic coarctation proximal to the renal arteries (Coarc, n = 8) and compared with sham-operated rats (Sham, n = 6). Renal renin distribution was determined by immunocytochemistry using a specific polyclonal antibody against rat renin. Renin mRNA was assessed by in situ hybridization to a 35S-labeled oligonucleotide complementary to rat renin mRNA. Kidney AT1 mRNA levels were determined by Northern analysis using a 1,133-base pair rat AT1 cDNA. Femoral arterial blood pressure, measured 24 h after surgery, was lower in Coarc than in Sham rats (75 +/- 5.4 vs. 122 +/- 2.3 mmHg, P < 0.05). Aortic coarctation increased the percent of juxtaglomerular apparatuses (%JGA) containing renin and its mRNA (85 +/- 2.5 and 66 +/- 2.8 vs. 49 +/- 5.3 and 36 +/- 1.7%, Coarc vs. Sham, P < 0.05) and the intensity of hybridization signals (497 +/- 89 vs. 71 +/- 12 grains/JGA, Coarc vs. Sham, P < 0.05). In addition, recruitment of renin gene expressing cells was observed along afferent arterioles in Coarc rats, whereas renin and its mRNA were limited to the JGAs in Sham rats. Renal AT1 receptor gene expression was threefold lower in Coarc than in Sham rats. We conclude that reduction of perfusion pressure after abdominal aortic coarctation acutely enhances renin gene expression and downregulates AT1 receptor gene expression.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

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↗