Effect of 6-aminonicotinamide on renin release in isolated rat kidney: possible role for the pentose pathway

1985 ◽  
Vol 249 (2) ◽  
pp. F213-F219
Author(s):  
S. G. Rostand ◽  
J. Work
Keyword(s):  
Rat Kidney ◽  
Renin Secretion ◽  
Renin Release ◽  
Sprague Dawley ◽  
Bicarbonate Buffer ◽  
Rate Limiting Step ◽  
Sprague Dawley Rats ◽  
Glucose 6 Phosphate Dehydrogenase ◽  
Renin Content ◽  
Pentose Pathway

To study the association between renal renin release and the pentose pathway, we perfused nonfiltering kidneys from Sprague-Dawley rats with Krebs-Ringer bicarbonate buffer containing 5 mM glucose and 14 g/100 ml bovine serum albumin in the presence or in the absence of 0.25 mM 6-aminonicotinamide (6AN), an inhibitor of glucose-6-phosphate dehydrogenase, the rate-limiting step of the pentose pathway. Eleven kidneys perfused in the absence of 6AN had a renin secretion rate of 7.4 +/- 2.2 ng ANG I X min-1 X ml-1. In six kidneys perfused in the presence of 6AN, renin release was depressed to 0.56 +/- 0.24 ng ANG I X min-1 X ml-1. The renal renin content for four control kidneys was 56 +/- 3.3 ng ANG I X mg-1 X h-1 while in four kidneys perfused with 6AN renal renin content was lower, 35 +/- 2.9 ng ANG I X mg-1 X h-1. In the presence of 5 mM lactate, the renin release of eight nonfiltering kidneys was 0.31 +/- 0.06 ng ANG I X min-1 X ml-1. The addition of 6AN did not further depress renin secretion in the presence of lactate. 6-Aminonicotinamide also completely blocked furosemide-stimulated renin release without having any effect on glomerular filtration rate or furosemide-induced natriuresis. However, 6AN did not inhibit stimulation of renin secretion by isoproterenol. We conclude that 6-aminonicotinamide interferes with renin release by nonfiltering kidneys and also inhibits furosemide-stimulated renin release but does not affect beta-adrenergic-stimulated renin secretion. Glucose but not lactate is important for maintaining augmented rates of renin secretion in nonfiltering kidneys. 6-Aminonicotinamide significantly reduced renal renin content in the presence of glucose.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibition of renin release by 14,15-epoxyeicosatrienoic acid in renal cortical slices

1990 ◽  
Vol 258 (2) ◽  
pp. E269-E274 ◽  
Author(s):  
W. L. Henrich ◽  
J. R. Falck ◽  
W. B. Campbell
Keyword(s):  
High Performance ◽  
Inhibitory Action ◽  
Rat Kidney ◽  
Renin Release ◽  
Gas Chromatography Mass Spectrometry ◽  
Epoxyeicosatrienoic Acid ◽  
Sprague Dawley ◽  
Cyclic Monophosphate ◽  
Sprague Dawley Rats ◽  
Cortical Slices

The effects of products of the cytochrome P-450 epoxygenase pathway of arachidonate metabolism on renin have not been previously examined. Initial high-performance liquid chromatography and gas chromatography-mass spectrometry studies documented the synthesis of four epoxyeicosatrienoic acid (EET) regioisomers of epoxygenase in superficial cortical slices from male Sprague-Dawley rats. Each regioisomer was tested for effects on both isoproterenol (ISO)-stimulated and basal renin secretion from cortical slices. ISO increased renin release significantly (169%, P less than 0.01) in all incubations; 14,15-EET (10(-6) M) significantly reduced this increase in stimulated renin release to 47%. The 5,6-, 8,9-, and 11,12-EETs did not significantly affect renin release. Basal renin release was not affected by any of the four EETs. To examine the mechanism of this inhibitory action, the effects of 14,15-EET on tissue adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 5'-cyclic monophosphate (cGMP) concentrations were measured. Tissue cAMP concentrations were sharply increased (4.75-fold, P less than 0.001) by ISO; 14,15-EET did not blunt this increase significantly. ISO and 14,15-EET did not affect tissue cGMP concentrations. Incubation of [14C]EET with cortical slices resulted in only 10% conversion of the 14,15-EET to 14,15-dihydroxyeicosatrienoic acid (DHET) (diol) after 90 min; no other metabolites were observed. The 14,15 DHET did not alter either basal or stimulated renin release. These studies document the synthesis of EETs in rat kidney and demonstrate a direct effect of the 14,15-EET to inhibit stimulated renin release. This inhibitory action occurs without an effect on tissue cAMP or cGMP concentrations.

Renin in thymus, gut, hindlimb, and adrenal of (mRen-2)27 and normal rats: secretion and content studies

1999 ◽  
Vol 277 (4) ◽  
pp. E639-E646 ◽  
Author(s):  
Pei Rong ◽  
Jennifer L. Wilkinson-Berka ◽  
Sandford L. Skinner
Keyword(s):  
Plasma Level ◽  
Plasma Potassium ◽  
High Plasma ◽  
Renin Secretion ◽  
Sprague Dawley ◽  
Low Level ◽  
Active Renin ◽  
Sprague Dawley Rats ◽  
Arteriovenous Difference ◽  
Renin Content

Thymic ablation and assay of organ renin revealed that one-third of the increasing plasma level of active renin after removal of kidneys and adrenals from Ren-2 rats originates from the thymus. Splanchnic arteriovenous difference and renin content indicate that gut can account for the remainder. Secretion of active renin from these sites correlated significantly with increasing plasma potassium. Prorenin was not secreted from these sites or from hindlimb in amounts sufficient to raise the plasma level, and yet plasma prorenin remained higher than active renin throughout the 12-h protocol. The source of prorenin that accounts for the high plasma prorenin phenotype of the intact conscious Ren-2 rat was not specifically identified. When sensitive assays were used, a low level of active renin secretion from thymus and gut was also apparent 12 h after removal of kidneys and adrenals in normal Sprague-Dawley rats, and plasma prorenin was at this time higher than active renin. A likely source of this extrarenal, extra-adrenal renin is the macrophage.

Metabolism of arginine by the isolated perfused rat kidney

1978 ◽  
Vol 235 (4) ◽  
pp. F376-F380 ◽  
Author(s):  
G. O. Perez ◽  
M. Epstein ◽  
B. Rietberg ◽  
R. Loutzenhiser
Keyword(s):  
Amino Acids ◽  
Rat Kidney ◽  
Sprague Dawley ◽  
Bicarbonate Buffer ◽  
Net Production ◽  
Isolated Perfused Rat Kidney ◽  
Guanidine Derivatives ◽  
Sprague Dawley Rats ◽  
Perfused Rat Kidney ◽  
Guanidinosuccinic Acid

In order to evaluate the renal contribution to the metabolism of arginine, we have evaluated its biosynthesis and catabolism in the isolated perfused rat kidney. The kidneys of eight male Sprague-Dawley rats were perfused with Krebs-Ringer-bicarbonate buffer containing albumin and amino acids. Twenty-five muCi of L-[guanidino-14C]arginine or 25 muCi L-[guanidino-14C]citrulline were added to the system and radiochromatograms of the perfusate were obtained at 0, 30, 60, and 90 min. Perfusate levels of urea, creatine, and guanidine derivatives were measured with high-pressure liquid chromatography. During perfusion there was net utilization of arginine and net production of creatine, guanidinoacetic acid (GAA) and guanidinosuccinic acid (GSA). The guanidino carbon of arginine was incorporated by the kidney into urea, creatine GSA, GAA, and guanidinobutyric acid. The production of 14C-labeled urea from L-[guanidino-14C]citrulline was substantially lower than that previously demonstrated in the liver, while that of arginine was approximately 20 times greater. These studies demonstrate the important contribution of the kidney to the synthesis and metabolism of arginine.

Sepsis induces changes in the expression and distribution of Toll-like receptor 4 in the rat kidney

2006 ◽  
Vol 290 (5) ◽  
pp. F1034-F1043 ◽  
Author(s):  
Tarek M. El-Achkar ◽  
Xiaoping Huang ◽  
Zoya Plotkin ◽  
Ruben M. Sandoval ◽  
Georges J. Rhodes ◽  
...  
Keyword(s):  
Rat Kidney ◽  
Expression Patterns ◽  
Cecal Ligation ◽  
Proximal Tubules ◽  
Microbial Pathogens ◽  
Sprague Dawley ◽  
Renal Vasculature ◽  
Two Photon Microscopy ◽  
Sprague Dawley Rats ◽  
Cellular Signal

Toll-like receptors (TLRs) are now recognized as the major receptors for microbial pathogens on cells of the innate immune system. Recently, TLRs were also identified in many organs including the kidney. However, the cellular distribution and role of these renal TLRs remain largely unknown. In this paper, we investigated the expression of TLR4 in a cecal ligation and puncture (CLP) model of sepsis in Sprague-Dawley rats utilizing fluorescence microscopy. In sham animals, TLR4 was expressed predominantly in Tamm-Horsfall protein (THP)-positive tubules. In CLP animals, TLR4 expression increased markedly in all tubules (proximal and distal), glomeruli, and the renal vasculature. The staining showed a strong apical distribution in all tubules. A moderately less intense cellular signal colocalized partially with the Golgi apparatus. In addition, kidneys from septic rats showed increased expression of CD14 and THP. They each colocalized strongly with TLR4, albeit in different tubular segments. We also imaged the kidneys of live septic animals with two-photon microscopy after fluorescent lipopolysaccharide (LPS) injection. Within 10 min, LPS was seen at the brush border of some proximal tubules. Within 60 min, LPS was fully cytoplasmic in proximal tubules. Conversely, distal tubules showed no LPS uptake. We conclude that TLR4, CD14, and THP have specific renal cellular and tubular expression patterns that are markedly affected by sepsis. Systemic endotoxin can freely access the tubular and cellular sites where these proteins are present. Therefore, locally expressed TLRs and other interacting proteins could potentially modulate the renal response to systemic sepsis.

scholarly journals Alteration of the Fatty Acid Metabolism in the Rat Kidney Caused by the Injection of Serum from Patients with Collapsing Glomerulopathy

Biomedicines ◽  
2020 ◽  
Vol 8 (10) ◽  
pp. 388
Author(s):  
Elizabeth Soria-Castro ◽  
Verónica Guarner-Lans ◽  
María Elena Soto ◽  
María del Carmen Avila-Casado ◽  
Linaloe Manzano Pech ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Acid Metabolism ◽  
Rat Kidney ◽  
Group Iv ◽  
Sprague Dawley ◽  
Group Iii ◽  
Collapsing Glomerulopathy ◽  
Fa Composition ◽  
Group I ◽  
Sprague Dawley Rats

Patients with collapsing glomerulopathy (CG) have marked proteinuria that rapidly progresses to chronic renal failure. In this study, we investigated if the nephropathy produced in a rat model by the injection of serum from CG patients induced alterations in fatty acid (FA) metabolism. Twenty-four female Sprague-Dawley rats were divided into four groups of six rats each: Group I, control rats (C); Group II, rats that received injections of 1 mL of 0.9% NaCl saline solution (SS); Group III, rats injected with 25 mg/mL of serum from healthy subjects (HS); and Group IV, rats injected with 25 mg/mL of serum from CG patients. In all groups, the systolic blood pressure (SBP), proteinuria, creatinine clearance (CC), cholesterol and total FA composition in the kidney and serum were evaluated. The administration of serum from CG patients to rats induced glomerular collapse, proteinuria, reduced CC and elevated SBP (p ≤ 0.01) in comparison with the C, SS and HS rats. The FA composition of the serum of rats that received the CG serum showed an increase in palmitic acid (PA) and a decrease in arachidonic acid (AA) when compared to serum from HS (p ≤ 0.02). In rats receiving the CG serum, there was also a decrease in the AA in the kidney but there was an increase in the PA in the serum and kidney (p ≤ 0.01). These results suggest that the administration of serum from CG patients to rats induces alterations in FA metabolism including changes in PA and in AA, which are precursors for the biosynthesis of the prostaglandins that are involved in the elevation of SBP and in renal injury. These changes may contribute to collapsing glomerulopathy disease.

Glucose-6-phosphate dehydrogenase and renin in kidneys of hypertensive or adrenalectomized rats

1959 ◽  
Vol 197 (4) ◽  
pp. 869-872 ◽  
Author(s):  
R. Hess ◽  
F. Gross
Keyword(s):  
Enzymatic Activity ◽  
Rat Kidney ◽  
Juxtaglomerular Apparatus ◽  
Macula Densa ◽  
Sodium Balance ◽  
Normal Rat ◽  
Distal Tubules ◽  
Glucose 6 Phosphate Dehydrogenase ◽  
Renin Content ◽  
Intact Rats

Using a histochemical method, moderately strong glucose-6-phosphate dehydrogenase activity can be demonstrated in the macula densa of the distal tubules in the normal rat kidney. In rats rendered hypertensive by overdosage with cortexone (DOC) and saline, this enzymatic activity was found to decrease almost to zero within 4 weeks. This change was more marked in unilaterally nephrectomized animals than in intact rats. Measured by bioassay, the renin content of kidney extracts from the same animals was found to decrease simultaneously with the loss of enzymatic activity in the macula cells. The reverse effect, a marked increase in activity of the macula densa, was obtained in adrenalectomized animals. It is suggested that both the macula densa cells and the juxtaglomerular apparatus are parts of a system which respond similarly to changes in sodium balance and which may be related to the formation of renin.

Ontogeny of glycine transport in isolated rat renal tubules

1977 ◽  
Vol 233 (3) ◽  
pp. F241-F246
Author(s):  
K. S. Roth ◽  
S. M. Hwang ◽  
J. W. London ◽  
S. Segal
Keyword(s):  
Rat Kidney ◽  
Renal Tubules ◽  
Sprague Dawley ◽  
Entry Rate ◽  
Glycine Uptake ◽  
Adult Rat ◽  
High Affinity ◽  
Sprague Dawley Rats ◽  
Rate Kinetics ◽  
Isolated Renal Tubule

Isolated renal tubule preparations were made from newborn Sprague-Dawley rats and used to study initial entry rate kinetics of glycine. The results were compared to those obtained in the isolated tubule preparation from the adult rat kidney. While initial rates of glycine uptake were identical for newborn and adult tubules, significant differences in influx kinetics were demonstrated. Of the two apparent transport Km systems shown to be present in the newborn tubule, the high-affinity, low-capacity system accounts for about 40% of total glycine uptake at physiologic concentrations. The high-affinity, low-capacity system of the adult tissue accounts for about 10% of total uptake at the same concentration range. The data lend strength to the argument against the concept that the physiologic hyperglycinuria of the newborn rat is due to either impaired ability to concentrate glycine intracellularly or to absence of one or more transport mechanisms for glycine.

Mechanism of prostaglandin E2-induced increase of proximal sodium reabsorption in the rat

1990 ◽  
Vol 258 (1) ◽  
pp. R82-R86 ◽  
Author(s):  
Y. Kinoshita ◽  
F. G. Knox
Keyword(s):  
Angiotensin Ii ◽  
Prostaglandin E2 ◽  
Rat Kidney ◽  
Sodium Reabsorption ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Convoluted Tubules ◽  
Stimulation Of ◽  
Interstitial Infusion

Prostaglandin E2, when infused directly into the renal interstitium, enhances sodium reabsorption by the superficial proximal convoluted tubules of anesthetized Sprague-Dawley rats. The present study was designed to investigate the role of angiotensin II in the prostaglandin E2-induced stimulation of proximal sodium reabsorption. Micropuncture at the superficial late proximal tubule demonstrated a significant increase in the fractional reabsorption of sodium from 39.9 +/- 2.3% in control conditions to 51.8 +/- 3.0% (n = 9, P less than 0.01) during the renal interstitial infusion of prostaglandin E2. The stimulatory effect of prostaglandin E2 on proximal sodium reabsorption was markedly attenuated by pretreatment with saralasin. During intravenous saralasin infusion, prostaglandin E2 did not significantly change the fractional reabsorption of sodium from 42.2 +/- 5.8 to 45.4 +/- 6.0% (n = 7, NS). In summary, the stimulatory effect of renal interstitial infusion of prostaglandin E2 on proximal sodium reabsorption was attenuated by pretreatment with saralasin. Therefore renal interstitial infusion of prostaglandin E2 may enhance proximal sodium reabsorption, at least in part, through stimulation of angiotensin II production in the rat kidney.

scholarly journals Some nutritional properties of unrefined sugar and its promotion of the survival of new-born rats

1985 ◽  
Vol 54 (3) ◽  
pp. 593-603 ◽  
Author(s):  
Eisa Omer Ahmed ◽  
Yudkin John
Keyword(s):  
Fatty Acid Synthetase ◽  
Female Rats ◽  
Male Rats ◽  
Blood Cholesterol ◽  
Maize Starch ◽  
Sprague Dawley ◽  
Brown Sugar ◽  
Sprague Dawley Rats ◽  
Male Wistar Rats ◽  
Glucose 6 Phosphate Dehydrogenase

1. The claims that rats fed on diets with ‘brown sugar’ (unrefined muscovado) perform better in a number of ways than do rats fed on refined white sugar (sucrose) have been examined.2. Male Wistar rats were fed on purified diets from weaning, in which the carbohydrate component was either maize starch or unrefined sugar or sucrose. The sugars produced no differences in growth rate, body composition, or the weights of liver or kidneys. Compared with sucrose, unrefined sugar produced an increase in blood cholesterol and in the activity of hepatic fatty acid synthetase, and a greater increase in blood triglyceride. In confirmation of earlier results, rats fed on either sugar had heavier livers and kidneys, increased activity of hepatic glucose-6-phosphate dehydrogenase (EC 1.1.1.49) and a higher concentration of plasma triglyceride compared with rats fed on maize starch.3. Female Sprague-Dawley rats were fed on the same three diets as the male rats, and mated when they weighed about 200 g. No difference was seen in their ability to mate, the progress of pregnancies, or the sizes of the litters. Does fed on unrefined sugar produced litters of higher viability than did does fed on starch or sucrose. Survival was between 85 and 100% with unrefined sugar and between 30 and 75% with starch or sucrose.4. Unrefined muscovado sugar has thus been shown to contain a factor required by female rats for the proper viability of their pups. This may be the same ‘Reproductive Factor R’ as that described by Wiesner & Yudkin (1951). In certain circumstances, unrefined muscovado sugar might therefore contribute to the nutritional value of a human diet, although in what circumstances, in what respect and to what extent it might do so, is by no means clear.

scholarly journals Contribution of cytochrome P-450 4A1 and 4A2 to vascular 20-hydroxyeicosatetraenoic acid synthesis in rat kidneys

1999 ◽  
Vol 276 (2) ◽  
pp. F246-F253 ◽  
Author(s):  
Mong-Heng Wang ◽  
Hui Guan ◽  
Xuandai Nguyen ◽  
Barbara A. Zand ◽  
Alberto Nasjletti ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Rat Kidney ◽  
Acid Synthesis ◽  
Biologically Active ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Antisense Odns ◽  
Cytochrome P 450

20-Hydroxyeicosatetraenoic acids (20-HETE), a biologically active cytochrome P-450 (CYP) metabolite of arachidonic acid in the rat kidney, can be catalyzed by CYP4A isoforms including CYP4A1, CYP4A2, and CYP4A3. To determine the contribution of CYP4A isoforms to renal 20-HETE synthesis, specific antisense oligonucleotides (ODNs) were developed, and their specificity was examined in vitro in Sf9 cells expressing CYP4A isoforms and in vivo in Sprague-Dawley rats. Administration of CYP4A2 antisense ODNs (167 nmol ⋅ kg body wt−1 ⋅ day−1iv for 5 days) decreased vascular 20-HETE synthesis by 48% with no effect on tubular synthesis, whereas administration of CYP4A1 antisense ODNs inhibited vascular and tubular 20-HETE synthesis by 52 and 40%, respectively. RT-PCR of microdissected renal microvessel RNA indicated the presence of CYP4A1, CYP4A2, and CYP4A3 mRNAs, and a CYP4A1-immunoreactive protein was detected by Western analysis of microvessel homogenates. Blood pressure measurements revealed a reduction of 17 ± 6 and 16 ± 4 mmHg in groups receiving CYP4A1 and CYP4A2 antisense ODNs, respectively. These studies implicate CYP4A1 as a major 20-HETE synthesizing activity in the rat kidney and further document the feasibility of using antisense ODNs to specifically inhibit 20-HETE synthesis and thereby investigate its role in the regulation of renal function and blood pressure.

Sign in / Sign up

Export Citation Format

Share Document