Isolated bilateral tarsal navicular fracture-dislocation.
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Adult↗
Biomedical subjects
R A Gomez
Publications and source records attributed to R A Gomez.
Use of interventional radiology for hypertension due to renal artery stenosis in children.
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Angioplasty, Balloon↗
Molecular and cellular aspects of renin during kidney ontogeny.
The activity of the renin-angiotensin system is subjected to remarkable developmental changes. Circulating as well as renal concentrations of renin are high in early life, decreasing progressively as maturation evolves. This review summarizes the current molecular framework underlying those changes during kidney development. Evidence is presented demonstrating that expression of the renin gene is developmentally regulated. Renin messenger ribonucleic acid (mRNA) levels are higher in fetuses and newborns than in adult mammals. As maturation progresses, the distribution of renin and its mRNA shifts from large intrarenal arteries in the fetus to the classic juxtaglomerular localization in the adult. Potential explanations for these changes as well as the cytosolic events mediating renin release and gene expression are discussed. Evidence is also presented demonstrating that under diverse physiologic and pathologic conditions the adult kidney vasculature has the capability to recruit renin gene expressing and/or containing cells. Throughout, an effort has been made to identify gaps in our knowledge. Not without bias, we hope that future research in this area will lead to a better understanding of the biology of renin in the developing as well as the adult individual.
Angiotensins↗
Spatial association of renin-containing cells and nerve fibers in developing rat kidney.
The development of renin-containing cells and nerve fibers was studied in Sprague-Dawley rat kidneys during the last third of gestation and the first 15 days of postnatal life. Kidney tissue sections were stained for nerve fibers or double stained employing an anti-rat renin polyclonal antibody and a monoclonal antibody (TUJ1) directed against a neuron-specific class III beta-tubulin isotype. Renin-containing cells and nerve fibers were detected at 17 days of gestation, in close spatial relationship along the main branches of the renal artery. During fetal life, renin-containing cells and nerve fibers were spatially associated along arcuate and interlobular arteries, renin-containing cells being also present throughout the entire length of afferent arterioles supplying juxtamedullary glomeruli. During postnatal life the distribution of renin-containing cells progressively shifted to a restricted juxtaglomerular position in afferent arterioles. Simultaneously, density and organization of nerve fibers increased with age along the arterial vascular tree. Our results suggest that innervation of renin-containing cells is present in fetal life and follows the centrifugal pattern of renin distribution and nephrovascular development.
Animals↗
Shuttle-box deficits induced by chronic variable stress: reversal by imipramine administration.
Escape performance in a shuttle-box task was evaluated in rats chronically exposed to a series of unpredictable stressors either during 14 or 7 consecutive days. Failure in escape responses was observed when animals were subjected to both regimes of variable aversive situations. The association between chronic exposure to unpredictable stressors with imipramine resulted in a significant reversal of escape deficits. Furthermore, animals submitted to repeated immobilization sessions during 7 days presented similar escape response to control rats. A possible involvement of beta-adrenergic sites on this behavioral response is discussed.
Animals↗
Differences in hippocampal synaptic plasticity in rats with inborn high or low learning ability may be related to different sensitivity of aspartate receptors.
Rats with an inborn high (HP) or low (LP) learning capacity were used to study the sensitivity to the blocking effect of 2-amino-phosphonopentanoic acid (AP5; 10 and 20 microM) on long-term potentiation (LTP) produced in hippocampal slices by a 1-s tetanus at 200 Hz. The potential evoked by stimulation of the perforant path was recorded from the granule cell layer of the dentate gyrus in 400 microns slices perfused with standard Krebs' solution or the AP5. Under perfusion with 10 microM of AP5, in 100% of slices from HP rats, LTP generation was not blocked; when AP5 20 microM was used, in 85% of the cases LTP was not blocked. In 60% of slices from LP rats, AP5 10 microM and in 100% of the cases at 20 microM AP5 blocked LTP generation. These results are coherent with the hypothesis that the different inborn learning ability of HP and LP rats is related to the different population or sensitivity of N-methyl-D-aspartate (NMDA) receptors.
2-Amino-5-phosphonovalerate↗
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↗
Gangliosides improve synaptic transmission in dentate gyrus of hippocampal rat slices.
The effect of perfusion with gangliosides (1 x 10(-6) M) on the response evoked in the granule cell layer of dentate gyrus by stimulation of perforant path in hippocampal rat slices was studied. Gangliosides induced both a decrease in the frequency threshold of stimulation necessary to generate long-term potentiation (LTP) and greater potentiation than under control conditions. It is proposed that gangliosides improve the mechanisms responsible for synaptic plasticity which generate LTP.
Action Potentials↗
Molecular biology of components of the renin-angiotensin system during development.
Evidence for the expression of genes of the renin-angiotensin system (RAS) in the developing kidney is rapidly accumulating. We have recently demonstrated that the fetal kidney expresses the renin gene and that expression of the gene is developmentally regulated. Kidney renin messenger ribonucleic acid (mRNA) levels decrease markedly with maturation, and as maturation unfolds the intrarenal distribution of renin and its mRNA changes from large intrarenal arteries in the fetus to a restricted juxtaglomerular site in the adult animal. These findings demonstrate that renin is synthesized and stored in the aforementioned vascular segments and that expression of the renin gene follows the centrifugal pattern of nephrovascular development. In addition to storing renin, intact kidney microvessels release renin spontaneously and possess a functionally active adenylate cyclase whose stimulation results in a marked increase in renin release. The increase in renin enzymatic activity appears to be due to a recruitment of renin-releasing cells rather than to an increase in the amount of renin secreted per cell. Expression of the angiotensinogen (Ao) gene is also developmentally regulated. Ao mRNA levels are very low in the fetal liver, markedly increasing after parturition, suggesting that some of the complex neurohumoral changes surrounding extrauterine life may regulate the expression of the Ao gene. As in the adult animal, Ao is expressed in fetal kidney, brain and brown adipose tissue. The contribution of these organs to the fetal plasma pool of Ao remains to be determined. However, unlike the adult, the fetal liver may not be the primary source of circulating Ao in the fetus.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
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↗
In situ localization of renin and its mRNA in neonatal ureteral obstruction.
Angiotensin II is an important mediator of renal vasoconstriction resulting from chronic unilateral ureteral obstruction (UUO). Distribution of renin mRNA and immunoreactive renin (IR) was examined in kidneys of 1-mo-old Sprague-Dawley rats subjected to either sham operation (n = 21), left complete UUO (n = 21), or right uninephrectomy (UNX, n = 16) at 2 days of age. There were no differences among the three groups in mean arterial pressure or plasma renin activity. Unlike sham kidneys, in which IR was detected in less than 55% of juxtaglomerular apparatuses (JGA) and was confined to a juxtaglomerular location, IR in both kidneys of animals with UUO appeared in greater than 75% of JGA and extended along most of the length of the afferent arteriole (P less than 0.01). In contrast, IR in kidneys of UNX rats was localized to the JGA as in sham-operated animals. Compared with sham-operated kidneys, renal renin content was increased in the obstructed kidneys (P less than 0.01) but decreased in the intact opposite kidneys of UUO rats and in the remaining kidneys of UNX rats (P less than 0.05). Renin mRNA, detected by in situ hybridization histochemistry, was localized to the JGA in kidneys of all groups. However, the fraction of JGA containing detectable renin mRNA was higher in obstructed kidneys than in intact opposite, UNX, or sham kidneys (P less than 0.05). In conclusion, UUO alters intrarenal renin independent of the systemic renin-angiotensin system. The greater distribution of IR, increased renin content, and renin gene expression of kidneys with ipsilateral UUO are consistent with a role for renin-angiotensin in mediating the vasoconstriction resulting from UUO.
Animals↗
Recruitment of renin gene-expressing cells in adult rat kidneys.
To define whether angiotensin I-converting enzyme (ACE) inhibition affects the distribution of renin gene-expressing cells within the kidney, a control group of adult male Wistar-Kyoto rats (C, n = 7) was compared with a group of rats treated with enalapril (E, n = 6) for 5 days. Renin mRNA distribution was assessed using in situ hybridization to a 35S-labeled 28 mer oligonucleotide complementary to rat renin mRNA. Whereas in control rats renin mRNA was confined to a juxtaglomerular location, in enalapril-treated rats, renin mRNA extended proximally along the length of the afferent arteriole. The percent of visible afferent arteriolar length containing renin mRNA was higher in enalapril-treated (71.7 +/- 2.8%) than in control (49.6 +/- 2.1%) rats (P less than 0.0001). These findings were accompanied by an increase in the percent of juxtaglomerular apparatuses (JGAs) containing renin mRNA (71 +/- 2.2 vs. 49 +/- 2.9%; E vs. C, P less than 0.0001). Also, the intensity of the JGA hybridization signals was higher in enalapril-treated (757 +/- 59 grains/JGA) than in control (167 +/- 11 grains/JGA) rats (P less than 0.00001). We conclude that the increased kidney renin gene expression elicited by ACE inhibition is the result of an increase in renin mRNA content per JGA, an increase in the number of JGAs expressing the renin gene, and a recruitment of renin gene-expressing cells along the afferent arteriole.
Angiotensin-Converting Enzyme Inhibitors↗
Angiotensin II regulates renin gene expression.
We investigated the effect of angiotensin II (ANG II) and enalapril on accumulation of renin messenger RNA (mRNA) and on renal renin distribution (immunohistochemical analysis). Adult Wistar-Kyoto rats received enalapril (0.2 mg/ml) in distilled drinking water for 8 or 12 days. On day 5 of enalapril treatment, an osmotic minipump was implanted in the peritoneum that caused sustained release of ANG II (200 ng.kg-1.min-1) or vehicle (bovine serum albumin) for 3 or 7 days. Control rats received water for 8 or 12 days and osmotic minipump implantation (containing vehicle solution) on the 5th day. Renin mRNA was identified by hybridization with a 32P-labeled full-length complementary DNA and was detected by autoradiography. Enalapril treatment increased renal renin mRNA specific activity (renin mRNA/total RNA). Subsequent infusion of angiotensin II for 3 or 7 days decreased renal renin mRNA specific activity. In addition, renin immunostaining increased along the afferent arteriole after enalapril treatment; however, enalapril-induced spread of renin immunostaining was not inhibited by ANG II. Thus ANG II attenuates the accumulation of renin mRNA stimulated by enalapril treatment without alteration of renal renin distribution. The lack of effect of ANG II on renal renin distribution may be due to the length of turnover time for stored protein. These findings suggest the shortloop negative feedback of ANG II on renin reflects inhibition of renin synthesis by ANG II. Therefore, we propose that ANG II exerts a direct inhibitory effect on renin by regulation of renin gene expression in renal vasculature.
Aldosterone↗
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↗