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.

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)

Intrarenal Conversion of Prostaglandin F2α Into Prostaglandin E2 and Renin Release in the Isolated Perfused Rat Kidney

1980 ◽  
Vol 59 (s6) ◽  
pp. 117s-119s ◽  
Author(s):  
U. Schwertschlag ◽  
H. W. Seyberth ◽  
H. Müller ◽  
R. Grunewald ◽  
T. Erlenmaier ◽  
...  
Keyword(s):  
Prostaglandin E2 ◽  
High Performance ◽  
Rat Kidney ◽  
Prostaglandin F2α ◽  
Normal Diet ◽  
Renin Release ◽  
Gas Chromatography Mass Spectrometry ◽  
High Sodium ◽  
Sodium Diet ◽  
Low Sodium Diet

1. Isolated rat kidneys were perfused with a modified Krebs-Henseleit medium at constant pressure. 2. When prostaglandin F2α (PGF2α) was infused into these kidneys at 0.1 μmol/l (final concentration) PGF2α-derived prostaglandin E2 (PGE2) could be identified by high-performance liquid chromatography and combined gas chromatography-mass spectrometry. 3. The extent of this conversion of PGF2α into PGE2 during passage through the kidney is dependent on the salt history of the rats from which the kidneys were taken for perfusion: kidneys from rats kept on normal diet converted 10%, those from rats on a low sodium diet 5% and those from rats kept on a high sodium diet 11%. 4. These differences in conversion can account for the different increases in renin release after PGF2α infusion in these groups.

Relationship between PG and beta-adrenergic pathways to renin release in rat renal cortical slices

1984 ◽  
Vol 247 (3) ◽  
pp. E343-E348 ◽  
Author(s):  
W. L. Henrich ◽  
W. B. Campbell
Keyword(s):  
Renin Activity ◽  
Renin Release ◽  
Sprague Dawley ◽  
Beta Adrenergic ◽  
Beta Agonists ◽  
Sprague Dawley Rats ◽  
High Concentrations ◽  
Rat Renal Cortical Slices ◽  
Cortical Slices ◽  
Synergistic Increase

The precise importance of prostaglandin (PG) in the beta-adrenergic pathway to renin release is unresolved. Thus, we examined this question using renal cortical slices from Sprague-Dawley rats incubated in Krebs-Ringer bicarbonate mixture (KRB), KRB + isoproterenol (10(-5) M, ISO), or a solution containing KRB + ISO + either propranolol (PRO, 10(-5) M) or indomethacin (IN, 10(-5) M). Media samples were assayed for renin activity, 6-keto-PGF1 alpha (the stable metabolite of PGI2), and PGE2. ISO only increased renin release 1.96-fold; modest increments in 6-keto-PGF1 alpha and PGE2 also occurred. The addition of PRO prevented these increases. In the next series of studies, ISO again increased renin, but the addition of IN failed to modify this increase in renin release. However, IN did prevent any increase in 6-keto-PGF1 alpha or PGE2. Meclofenemate (10(-5) M) provided results similar to those of IN. PGI2 was found to stimulate the release of renin in concentrations of 10(-7) M. The combination of submaximal stimulatory concentrations of PGI2 (10(-6) M, a 1.6-fold increment) and ISO (10(-6) M, a 1.7-fold increment) produced a synergistic increase in renin release (2.84-fold). These results demonstrate that renal prostaglandins do not function as essential mediators of the beta-adrenergic pathway to renin release. Rather, high concentrations of prostaglandins may increase the renin-releasing action of beta-agonists, thereby modulating the release of renin.

scholarly journals Age-related decline in the taurine content of the skin in rodents

Amino Acids ◽  
2021 ◽  
Author(s):  
Tomohisa Yoshimura ◽  
Yuki Inokuchi ◽  
Chikako Mutou ◽  
Takanobu Sakurai ◽  
Tohru Nagahama ◽  
...  
Keyword(s):  
High Performance ◽  
Age Groups ◽  
Immunohistochemical Analysis ◽  
Sprague Dawley ◽  
Taurine Supplementation ◽  
Hairless Mice ◽  
Age Related ◽  
Sprague Dawley Rats ◽  
High Concentrations ◽  
Effects Of Aging

AbstractTaurine, a sulfur-containing amino acid, occurs at high concentrations in the skin, and plays a role in maintaining the homeostasis of the skin. We investigated the effects of aging on the content and localization of taurine in the skin of mice and rats. Taurine was extracted from the skin samples of hairless mice and Sprague Dawley rats, and the taurine content of the skin was determined by high-performance liquid chromatography (HPLC). The results of the investigation revealed that the taurine content in both the dermis and epidermis of hairless mice declined significantly with age. Similar age-related decline in the skin taurine content was also observed in rats. In contrast, the taurine content in the sole remained unchanged with age. An immunohistochemical analysis also revealed a decreased skin taurine content in aged animals compared with younger animals, although no significant differences in the localization of taurine were observed between the two age groups. Supplementation of the drinking water of aged mice with 3% (w/v) taurine for 4 weeks increased the taurine content of the epidermis, but not the dermis. The present study showed for the first time that the taurine content of the skin decreased with age in mice and rats, which may be related to the impairment of the skin homeostasis observed with aging. The decreased taurine content of the epidermis in aged animals was able to be rescued by taurine supplementation.

Ranitidine as an alcohol dehydrogenase inhibitor in acute methanol toxicity in rats

2009 ◽  
Vol 29 (2) ◽  
pp. 93-101 ◽  
Author(s):  
Amal A El-Bakary ◽  
Sahar A El-Dakrory ◽  
Sohayla M Attalla ◽  
Nawal A Hasanein ◽  
Hala A Malek
Keyword(s):  
Alcohol Dehydrogenase ◽  
High Performance ◽  
Negative Control Group ◽  
Positive Control ◽  
Negative Control ◽  
Control Group ◽  
Sprague Dawley ◽  
Blood Samples ◽  
Methanol Poisoning ◽  
Sprague Dawley Rats

Methanol poisoning is a hazardous intoxication characterized by visual impairment and formic acidemia. The therapy for methanol poisoning is alcohol dehydrogenase (ADH) inhibitors to prevent formate accumulation. Ranitidine has been considered to be an inhibitor of both gastric alcohol and hepatic aldehyde dehydrogenase enzymes. This study aimed at testing ranitidine as an antidote for methanol acute toxicity and comparing it with ethanol and 4-methyl pyrazole (4-MP). This study was conducted on 48 Sprague-Dawley rats, divided into 6 groups, with 8 rats in each group (one negative control group [C1], two positive control groups [C2, C3] and three test groups [1, 2 and 3]). C2, C3 and all test groups were exposed to nitrous oxide by inhalation, then, C3 group was given methanol (3 g/kg orally). The three test groups 1, 2 and 3 were given ethanol (0.5 g/kg orally), 4-MP (15 mg/kg intraperitoneally) and ranitidine (30 mg/kg intraperitoneally), respectively, 4 hours after giving methanol. Rats were sacrificed and heparinized, cardiac blood samples were collected for blood pH and bicarbonate. Non-heparinized blood samples were collected for formate levels by high performance liquid chromatography. Eye balls were enucleated for histological examination of the retina. Ranitidine corrected metabolic acidosis (p = .025), decreased formate levels (p = .014) and improved the histological findings in the retina induced by acute methanol toxicity.

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.

Plasminogen activator inhibitor-1 rises after hemorrhage in rats

1995 ◽  
Vol 268 (6) ◽  
pp. E1065-E1069 ◽  
Author(s):  
M. Yamashita ◽  
D. N. Darlington ◽  
E. J. Weeks ◽  
R. O. Jones ◽  
D. S. Gann
Keyword(s):  
Plasminogen Activator ◽  
High Performance ◽  
Plasminogen Activator Inhibitor ◽  
Tissue Type ◽  
Sprague Dawley ◽  
Plasminogen Activator Inhibitor 1 ◽  
Sprague Dawley Rats ◽  
Type Plasminogen Activator ◽  
Activator Inhibitor ◽  
Pai 1

Large hemorrhage leads to hypercoagulability, a phenomenon that has never been well explained. Because an elevation of plasminogen activator inhibitor (PAI)-1 increases procoagulant activity, we have determined whether plasma PAI activity and tissue PAI-1 mRNA are elevated after hemorrhage. Sprague-Dawley rats were bled (20 or 15 ml/kg) 4 days after cannulation. Plasma PAI activity was determined by the capacity of plasma to inhibit tissue-type plasminogen activator activity. Changes of PAI-1 mRNA in various tissues were detected by high-performance liquid chromatography after reverse transcription and polymerase chain reaction. Hemorrhage (20 ml/kg) significantly elevated plasma PAI activity at 0.5, 1, 2, 4, 6, and 8 h after hemorrhage and PAI-1 mRNA in liver at 1, 2, 4, and 6 h after hemorrhage. The PAI-1 message was also significantly elevated in lung, heart, and kidney at 4 h after hemorrhage. The increases of PAI-1 mRNA after 20 ml/kg hemorrhage were significantly greater than those after 15 ml/kg hemorrhage. These findings indicate that large hemorrhage can induce the increases in PAI activity and PAI-1 message and suggest that induction of PAI-1 may be involved in the thrombogenic responses observed after large hemorrhage.

Pharmacokinetic Interaction between Asari Radix et Rhizoma and Dried Ginger (Zingiber officinalis) in Rats

2021 ◽  
Vol 17 ◽  
Author(s):  
Xingxing Zhuang ◽  
Li Zhou ◽  
Renhua Miao ◽  
Shoudong Ni ◽  
Meng Li
Keyword(s):  
High Performance ◽  
Pharmacokinetic Interaction ◽  
Raw Material ◽  
Pharmacokinetic Parameters ◽  
Sprague Dawley ◽  
Active Components ◽  
Sprague Dawley Rats ◽  
Liquid Chromatography Tandem Mass ◽  
Student’S T ◽  
Student’S T Test

Introduction:: Asari Radix et Rhizoma (ARR) and dried ginger (Zingiber officinalis) (DG) are often used together in drug preparations in traditional Chinese medicine (TCM) to treat respiratory diseases including cold, bronchitis and pneumonia. Previous studies suggested that ARR and/or DG may influence the pharmacokinetics of other herbal components. In the current study, we examined pharmacokinetic interactions between ARR and DG in rats after oral administration. Methods:: We developed a method based on ultra-high-performance liquid chromatography-tandem mass spectrometry to simultaneously measure serum concentrations of two active components each in ARR (L-asarinin and sesamin) and DG (6-gingerol and 6-shogaol). Adult Sprague-Dawley rats were starved overnight, then given ARR extract, DO extract, or a co-decoction of ARR and DG by gastric gavage (6 g raw material per kg body weight; n = 6 per group). Blood samples were collected prior to drug administration and at the following times (h) afterward: 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 12.0 and 24.0. Pharmacokinetic parameters were compared using Student’s t test for independent samples. Results:: A simple, rapid, sensitive analytical method has been developed to detect four bioactive components simultaneously in the ARR-DG herbal pair. Pharmacokinetic parameters including Cmax, Tmax, T1/2 and AUC(0~t) were calculated using the non-compartmental model with the DAS 2.0 pharmacokinetic software. For L-asarinin, Tmax was 2.00 ± 0.00 h in ARR animals and 1.67±0.26 h in ARR-DG animals (P<0.05), T1/2 was 8.58 ± 1.75 h in ARR and 11.93 ± 2.13 h in ARR-DG (P<0.05). For 6-gingerol, Cmax was 350.48 ± 23.85 ng/mL in DG animals and 300.21 ± 20.02 ng/mL in ARR-DG (P<0.01), Tmax was 2.83 ± 0.41 h in DG and 2.17 ± 0.41 h in ARR-DG (P<0.05) and AUC(0~t) was 1.93 ± 0.15 mg/mL•h in ARR and 1.70 ± 0.15 mg/mL•h in ARR-DG (P<0.05). For 6-shogaol, Cmax was 390.28 ± 26.02 ng/mL in DG animals and 455.63 ± 31.01 ng/mL in ARR-DG (P<0.01), Tmax was 2.93 ± 0.10 h in DG and 1.92 ± 0.10 h in ARR-DG (P<0.01), T1/2 was 3.74 ± 0.29 h in DG and 3.28 ± 0.22 h in ARR-DG (P<0.01), and AUC(0~t) was 2.15 ± 0.18 mg/mL•h in DG and 2.73 ± 0.15 mg/mL•h in ARR-DG (P<0.01). Conclusions:: Pharmacokinetic interations between ARR and DG decrease Tmax, increase T1/2 but do not affect overall bioavailability of L-asarinin in ARR. The interactions in ARR-DG decrease Cmax and Tmax but increase T1/2 and AUC(0~t) of 6-gingerol in DG. The interactions increase Cmax and AUC(0~t) but decrease Tmax and T1/2 of 6- shogaol in DG. Interactions in ARR-DG do not affect the pharmacokinetics of sesamin.

scholarly journals Brain Metabolomics Reveal the Antipyretic Effects of Jinxin Oral Liquid in Young Rats by Using Gas Chromatography–Mass Spectrometry

Metabolites ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 6 ◽  
Author(s):  
Wenjuan Qian ◽  
Jinjun Shan ◽  
Cunsi Shen ◽  
Rui Yang ◽  
Tong Xie ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Gas Chromatography ◽  
Young Male ◽  
Gas Chromatography Mass Spectrometry ◽  
Sprague Dawley ◽  
Chromatography Mass Spectrometry ◽  
Sprague Dawley Rats ◽  
Oral Liquid ◽  
Pg E2 ◽  
Potential Biomarkers

Pyrexia is considered as a part of host’s defense response to the invasion of microorganisms or inanimate matter recognized as pathogenic or alien, which frequently occurs in children. Jinxin oral liquid (JXOL) is a traditional Chinese medicine formula that has been widely used to treat febrile children in China. Experimental fever was induced by injecting yeast into young male Sprague-Dawley rats (80 ± 20 g) and the rectal temperature subsequently changed. Four hours later, the excessive production of interleukin (IL)-1β and prostaglandin (PG) E2 induced by yeast was regulated to normal by JXOL administration. A rat brain metabolomics investigation of pyrexia of yeast and antipyretic effect of JXOL was performed using gas chromatography-mass spectrometry (GC-MS). Clear separation was achieved between the model and normal group. Twenty-two significantly altered metabolites were found in pyretic rats as potential biomarkers of fever. Twelve metabolites, significantly adjusted by JXOL to help relieve pyrexia, were selected out as biomarkers of antipyretic mechanism of JXOL, which were involved in glycolysis, purine metabolism, tryptophan mechanism, etc. In conclusion, the brain metabolomics revealed potential biomarkers in the JXOL antipyretic process and the associated pathways, which may aid in advanced understanding of fever and therapeutic mechanism of JXOL.

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.

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