Abstract：
:Animals treated with nitric oxide synthase (NOS) inhibitors exhibit marked hypersensitivity to the blood pressure lowering effects of exogenous nitric oxide (NO) donors. We used this model as a sensitive index to evaluate the relative importance of reduced biotransformation of glyceryl trinitrate (GTN) to NO in the development of nitrate tolerance. NOS-blockade hypertension using N(G)-nitro-L-arginine methyl ester (L-NAME) caused a marked enhancement of the mean arterial pressure (MAP) decrease mediated by GTN in nontolerant rats. However, even large doses of GTN were unable to change the MAP in GTN-tolerant, NOS-blockade hypertensive animals. In contrast, the MAP responses to the spontaneous NO donor sodium nitroprusside (SNP) were completely unaltered in either tolerant rats or tolerant NOS-blockade hypertensive animals, indicating that NO-dependent vasodilatory mechanisms remain intact despite the development of GTN tolerance. The MAP-lowering effects of GTN in NOS-blockade hypertensive animals were restored 48 h after cessation of chronic GTN exposure. These alterations in the pharmacodynamic response to GTN during tolerance development and reversal were associated with parallel changes in the pattern of GTN metabolite formation, suggesting that the activity of one or more enzymes involved in nitrate metabolism was altered as a consequence of chronic GTN exposure. These findings suggest that the vasodilation resulting from the vascular biotransformation of GTN to NO (or a closely related species) is severely compromised in nitrate-tolerant animals, and that although other mechanisms may contribute to the vascular changes observed following the development of GTN tolerance, decreased GTN bioactivation is likely the most important.
journal_name
Can J Physiol Pharmacoljournal_title
Canadian journal of physiology and pharmacologyauthors
Ratz JD,Adams MA,Bennett BMdoi
10.1139/y02-141subject
Has Abstractpub_date
2002-11-01 00:00:00pages
1106-18issue
11eissn
0008-4212issn
1205-7541journal_volume
80pub_type
杂志文章abstract：:An acidic proteinase was purified from human kidney cortex. The enzyme showed a molecular mass of 31 kDa by SDS-PAGE, 36 kDa by gel filtration, and isoelectric points of 5.2 and 6.1. The optimum pH for hydrolysis of bovine hemoglobin was about 3.5. Reverse-phase HPLC analysis of the incubation mixture of the enzyme wi...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：
更新日期：1997-06-01 00:00:00
abstract：:Although dual endothelin receptor antagonists (ERAs) show great promise for treating various conditions, their propensity to induce liver injury limits their clinical usage. Inflammation and fibrosis are important processes in liver responses to injury and it has been suggested that they and dual ERA-induced liver inj...
journal_title：Canadian journal of physiology and pharmacology
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journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y85-102
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abstract：:The beneficial hypolipidemic and antioxidant influences of the dietary spice compounds curcumin and capsaicin were evaluated. Curcumin, capsaicin, or their combination were included in the diet of high-(30%)-fat-fed rats for 8 weeks. Dietary high-fat-induced hypertriglyceridemia was countered by dietary curcumin, caps...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y07-044
更新日期：2007-06-01 00:00:00
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journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y92-088
更新日期：1992-05-01 00:00:00
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journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y91-047
更新日期：1991-02-01 00:00:00
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journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/cjpp-2015-0068
更新日期：2015-08-01 00:00:00
abstract：:Ah receptor in hepatic cytosols from adult cynomolgus monkeys (Macaca fasicularis) was identified and quantitated by its binding of the highly toxic chemical 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and the carcinogens 3-methylcholanthrene, benzo[a]pyrene, and dibenz[a,h]anthracene. The concentration of Ah receptor ...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y84-216
更新日期：1984-10-01 00:00:00
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journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y88-052
更新日期：1988-04-01 00:00:00
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journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y92-184
更新日期：1992-10-01 00:00:00
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journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章,评审
doi：10.1139/y90-155
更新日期：1990-07-01 00:00:00
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journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y77-034
更新日期：1977-04-01 00:00:00
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journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y82-226
更新日期：1982-12-01 00:00:00
abstract：:Nitric oxide (NO) production occurs through oxidation of the amino acid L-arginine by NO synthase (NOS). NO inhibits platelet activation by increasing the levels of cyclic guanosine monophosphate (cGMP), thus maintaining vascular homeostasis. Our group previously demonstrated (da Silva et al. 2005) an enhancement of t...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y10-111
更新日期：2011-02-01 00:00:00
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journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章,评审
doi：10.1139/y87-119
更新日期：1987-04-01 00:00:00
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journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y95-116
更新日期：1995-07-01 00:00:00
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journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y75-138
更新日期：1975-12-01 00:00:00
abstract：:In recent experiments in conscious lambs, we showed that in addition to its well-known natriuretic and diuretic effects, i.v. injection of 2 mg/kg of furosemide resulted in a sustained increase in heart rate and an age-dependent increase in plasma renin activity. To determine whether these responses were dose dependen...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：
更新日期：1997-09-01 00:00:00
abstract：:The effects of the dopamine type-2 receptor (D-2) antagonist domperidone on pituitary and brain amine concentrations and serum gonadotropin levels in the goldfish were investigated. Domperidone caused a long-lasting, dose-dependent depletion of dopamine in the goldfish pituitary. Pituitary concentrations of 5-hydroxyt...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y91-116
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journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y90-105
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journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y89-095
更新日期：1989-06-01 00:00:00
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journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y82-227
更新日期：1982-12-01 00:00:00
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journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y88-176
更新日期：1988-08-01 00:00:00
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journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y80-049
更新日期：1980-03-01 00:00:00
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journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章,评审
doi：10.1139/cjpp-2014-0413
更新日期：2015-03-01 00:00:00
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journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y05-042
更新日期：2006-03-01 00:00:00
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journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y90-238
更新日期：1990-12-01 00:00:00
abstract：:The aryl hydrocarbon receptor (AHR) has physiological roles in the absence of exposure to exogenous ligands, and mediates adaptive and toxic responses to the environmental pollutant 2,3,7,8-tetracholorodibenzo-p-dioxin (TCDD). A readily metabolized AHR agonist, 3-methylcholanthrene, disrupts the expression of mouse he...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y2012-099
更新日期：2012-10-01 00:00:00
abstract：:The aim of this study was to identify the key genes involved in the cardiac hypertrophy (CH) induced by pressure overload. mRNA microarray data sets GSE5500 and GSE18801 were downloaded from the Gene Expression Omnibus database, and differentially expressed genes (DEGs) were screened using the Limma package; then, fun...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/cjpp-2017-0585
更新日期：2018-08-01 00:00:00
abstract：:We characterized the innervation of isolated circular and longitudinal-oriented muscle strips from the nulliparous rabbit uterus and cervix by field stimulation (FS). FS with increasing frequency (2.5-50 pps) and voltage (2.5-70 V) caused graded increases in isometric contraction with no relaxation or inhibition of sp...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y89-131
更新日期：1989-08-01 00:00:00
