Inhibition of the formation of EETs and 20-HETE with 1-aminobenzotriazole attenuates pressure natriuresis

Santos, Elisabete Alcantara dos; Dahly-Vernon, Annette J.; Hoagland, Kimberly M.; Roman, Richard J.

doi:10.1152/ajpregu.00713.2003

Cited by 76 publications

(71 citation statements)

References 80 publications

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“…Treatment of rats with ABT has been shown to reduce renal excretion of sodium in response to elevated renal tubule pressure. It is proposed that this effect is attributed to blockade of P450-mediated arachidonic acid metabolism, decreased Na + -K + -ATPase activity, and internalization of NHE-3 protein from the brush border of the proximal tubule (Dos Santos et al, 2004). We speculate that altered arachidonic metabolism and the subsequent impact of water retention in the stomach are potential mechanisms for ABT-induced stomach enlargement and the altered gastric emptying rate.…”

Section: Discussionmentioning

confidence: 91%

1-Aminobenzotriazole Modulates Oral Drug Pharmacokinetics through Cytochrome P450 Inhibition and Delay of Gastric Emptying in Rats

et al. 2014

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The simultaneous effects of the cytochrome P450 inhibitor 1-aminobenzotriazole (ABT) on inhibition of in vivo metabolism and gastric emptying were evaluated with the test compound 7-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-3-(4-methoxy-2-methylphenyl)-2,6-dimethylpyrazolo [5,1-b]oxazole(NVS-CRF38), a novel corticotropin releasing factor receptor 1 (CRF 1 ) antagonist with low water solubility, and the reference compound midazolam with high water solubility in rats. Pretreatment of rats with 100 mg/kg oral ABT administered 2 hours before a semisolid caloric test meal markedly delayed gastric emptying. ABT increased stomach weights by 2-fold; this is likely attributable to a prosecretory effect because stomach concentrations of bilirubin were comparable in ABT and control groups. ABT administration decreased the initial systemic exposure of orally administered NVS-CRF38 and increased T max 40-fold, suggesting gastric retention and delayed oral absorption. ABT increased the initial systemic exposure of midazolam, however for orally (but not subcutaneously) administered midazolam, extensive variability in plasma-concentration time profiles was apparent. Careful selection of administration routes is recommended for ABT use in vivo, variable oral absorption of coadministered compounds can be expected due to a disturbance of gastrointestinal transit.

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Section: Discussionmentioning

confidence: 91%

1-Aminobenzotriazole Modulates Oral Drug Pharmacokinetics through Cytochrome P450 Inhibition and Delay of Gastric Emptying in Rats

et al. 2014

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“…1 Of these metabolites, 20-hydroxyecisatatraenoic acid (20-HETE) has been reported to inhibit sodium transport and promote natriuresis. 2,3 Studies in Dahl salt-sensitive (Dahl S) rats indicate that production of 20-HETE in the outer medulla is reduced and that this defect contributes to the development of salt-sensitive hypertension in this model. 4,5 Induction of the renal expression of Cyp4a enzymes in the kidney using fibrate compounds has been reported to lower blood pressure in spontaneously hypertensive rats (SHR) and stroke-prone SHR and Dahl S rats.…”

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confidence: 99%

Fenofibrate Prevents the Development of Angiotensin II–Dependent Hypertension in Mice

et al. 2005

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Abstract-Previous studies have indicated that the production of 20-hydroxyecisatatraenoic acid (20-HETE) is similar in the liver of C57/B6 mice and rats, but the renal production of 20-HETE is very low in this strain of mice. The present study examined the effects of induction of the renal production of 20-HETE with fenofibrate (FF) on the development of angiotensin II (Ang II)-dependent hypertension in C57BL/6J mice. The mice were divided into 4 groups and treated with vehicle (control), FF (90 mg/kg per day, IP), Ang II (1000 ng/kg per minute, SC), and Ang II plus FF. Mean arterial blood pressure (MAP) averaged 109Ϯ4 and 106Ϯ2 mm Hg in control and FF-treated mice (nϭ7). MAP was significantly increased in the Ang II-treated mice to 144Ϯ4 mm Hg (nϭ7). However, FF treatment prevented the development of Ang II-dependent hypertension, with MAP averaging 115Ϯ5 mm Hg in mice treated with both Ang II plus FF (nϭ7). Renal production of 20-HETE was very low in control (nϭ7) and Ang II-treated (nϭ7) mice and was increased by Ͼ2-fold in FF-treated (nϭ7) and Ang II plus FF-treated (nϭ7) mice. The levels of Cyp4A proteins were markedly increased in the kidneys of mice treated with FF and Ang II plus FF but not in the renal vasculature. These results suggest that upregulation of the production of 20-HETE in renal tubules may contribute to the blood pressure-lowering effects of FF treatment in Ang II-dependent hypertension in C57BL/6J mice. 1 Of these metabolites, 20-hydroxyecisatatraenoic acid (20-HETE) has been reported to inhibit sodium transport and promote natriuresis. 2,3 Studies in Dahl salt-sensitive (Dahl S) rats indicate that production of 20-HETE in the outer medulla is reduced and that this defect contributes to the development of salt-sensitive hypertension in this model. 4,5 Induction of the renal expression of Cyp4a enzymes in the kidney using fibrate compounds has been reported to lower blood pressure in spontaneously hypertensive rats (SHR) and stroke-prone SHR and Dahl S rats. 6,7 The reduction of blood pressure with clofibrate in Dahl S rats was also associated with the normalization of the pressurenatruretic response in this model. 8 In mice, the expression of Cyp4A proteins and renal 20-HETE production is reduced during the development of deoxycorticosterone acetate-salt hypertension. 9 Induction of the renal production of 20-HETE with bezafibrate lowered the blood pressure and improved renal hemodynamics in this model. 10 These studies suggest that a deficiency in the renal production of 20-HETE may promote the development of hypertension. More recently, we have reported that the renal production of 20-HETE is also very low in the kidney of C57BL/6J mice, 11 indicating that they may be a good model to determine the role of CYP metabolites of AA in the regulation of renal function and blood pressure. Thus, the present study examined the effects of induction of the renal production of 20-HETE with FF on the development of Ang II-dependent hypertension in C57BL/6J mice.

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“…Interestingly, 20-HETE has actions to reduce sodium transport and, like ET B receptor activation, has been implicated in saltdependent hypertension. [17][18][19][20][21] Previous studies have provided evidence that 20-HETE contributes to ET-1-mediated natriuretic responses. 22 Blockade of CYP4A and 20-HETE prevented the increase in urinary sodium excretion produced by ET-1.…”

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confidence: 99%

Peroxisome Proliferator-Activated Receptor-α Activation Reduces Salt-Dependent Hypertension During Chronic Endothelin B Receptor Blockade

et al. 2005

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Abstract-Endothelin B (ET B ) receptor stimulation inhibits sodium transport in a similar fashion as 20-HETE. Clofibrate, a peroxisome proliferator-activated receptor-␣ (PPAR-␣) agonist, increases protein expression of cytochrome P450 4A (CYP4A), which is responsible for 20-HETE synthesis in the kidney. Experiments were designed to determine whether clofibrate reduces hypertension associated with chronic ET B receptor blockade. Male Sprague-Dawley rats received either normal-salt (0.8% NaCl) or high-salt (8% NaCl) diet for 10 days. Female rats were fed a high-salt (8% NaCl) diet for 10 days. During the last 7 days, rats of both sexes were divided into 3 treatment groups: (1) [1][2][3] In the kidney, ET-1 is synthesized from a variety of cells such as vascular endothelium, mesangial cells, tubular epithelial cells, and medullary interstitium. 4 -10 The primary receptor subtype on renal tubular epithelial cells is the ET B receptor. 3 Studies have demonstrated that ET-1 stimulates sodium and water excretion through ET B receptor activation. 11 Consistent with a pronatriuretic function, our laboratory has shown that blocking ET B receptors causes salt-dependent hypertension along with elevated plasma ET-1 levels. 12,13 The latter effect is thought to be attributable to reduced clearance of ET-1 in the absence of ET B receptor availability.The role of cytochrome P450 (CYP450) hydroxylase metabolites in the maintenance of arterial pressure is complex because of their contrasting hypertensive and antihypertensive properties. 14 Clofibrate, a peroxisome proliferator activated receptor-␣ (PPAR-␣) agonist, has been shown to reduce arterial pressure in Dahl salt-sensitive rats on high salt diet by inducing the genes that code for CYP4504A (CYP4A) enzymes in the renal cortex. 15,16 CYP4A is the enzyme responsible for the synthesis of 20-HETE. Interestingly, 20-HETE has actions to reduce sodium transport and, like ET B receptor activation, has been implicated in saltdependent hypertension. [17][18][19][20][21] Previous studies have provided evidence that 20-HETE contributes to ET-1-mediated natriuretic responses. 22 Blockade of CYP4A and 20-HETE prevented the increase in urinary sodium excretion produced by ET-1. 23 Similarly, inhibition of 20-HETE formation in isolated proximal tubules prevented the blockade of ion transport produced by ET-1, indicating that 20-HETE acts as a second messenger of ET-1 in the proximal tubule. 23 Because the ET-1-mediated diuretic and natriuretic effects are through ET B activation, it is reasonable to presume that ET-1 stimulates 20-HETE formation through ET B receptors. The purpose of the present study was to determine the influence of PPAR-␣ activation and upregulation of CYP4A in the salt-sensitive hypertension produced by chronic ET B receptor blockade.

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Inhibition of the formation of EETs and 20-HETE with 1-aminobenzotriazole attenuates pressure natriuresis

Cited by 76 publications

References 80 publications

1-Aminobenzotriazole Modulates Oral Drug Pharmacokinetics through Cytochrome P450 Inhibition and Delay of Gastric Emptying in Rats

1-Aminobenzotriazole Modulates Oral Drug Pharmacokinetics through Cytochrome P450 Inhibition and Delay of Gastric Emptying in Rats

Fenofibrate Prevents the Development of Angiotensin II–Dependent Hypertension in Mice

Peroxisome Proliferator-Activated Receptor-α Activation Reduces Salt-Dependent Hypertension During Chronic Endothelin B Receptor Blockade

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