Abstract：
:Previous studies have demonstrated that the D-enantiomer of isoidide dinitrate (IIDN) is 10-fold more potent than the L-enantiomer for relaxation and cyclic GMP accumulation in isolated rat aorta. To test whether preferential biotransformation of D-IIDN to a species that activates guanylate cyclase is the basis for this observed enantioselectivity, paired segments of rat aorta were exposed to D- and L-IIDN and the tissue accumulation of the parent compound and the formation of their respective metabolites (D- and L-isoidide mononitrate, IIMN) were determined. The extent of relaxation of rat aorta following exposure to 2 microM D-IIDN was greater than that by L-IIDN over a 5-minute time course, and this was associated with a higher rate of D-IIDN biotransformation to D-IIMN at all time points. In addition, the rate of D-IIDN biotransformation was greater than that of L-IIDN at most IIDN concentrations tested. By contrast, the amount of D- and L-IIDN in the tissue was the same at all time points and concentrations tested, indicating that selective uptake of D-IIDN into blood vessels did not occur. When tissues were made tolerant to organic nitrate-induced relaxation by treatment with a high concentration of glyceryl trinitrate, the biotransformation of both D- and L-IIDN was attenuated. This suggests that mechanism-based biotransformation may be affected during tolerance development. Furthermore, the association of preferential D-IIDN biotransformation with its greater potency for vasodilation and cyclic GMP accumulation suggests than an enantioselective site for biotransformation is an important component of organic nitrate-induced vasodilation.
journal_name
Can J Physiol Pharmacoljournal_title
Canadian journal of physiology and pharmacologyauthors
Stewart DH,Hayward LD,Bennett BMdoi
10.1139/y89-225subject
Has Abstractpub_date
1989-11-01 00:00:00pages
1403-8issue
11eissn
0008-4212issn
1205-7541journal_volume
67pub_type
杂志文章abstract：:Cumulative data suggest the significant role of the renin-angiotensin system in the development of the pathological consequences of diabetes mellitus (DM). Newly synthesized AT2 receptor agonists gained importance as a target for creating new antihypertensives. The aim of the present work was to study the effects of p...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/cjpp-2017-0428
更新日期：2018-05-01 00:00:00
abstract：:Allicin, the active substance of garlic, exerts a broad spectrum of pharmacological activities and is considered to have potential therapeutic applications. The present study was designed to investigate the possible beneficial effects of allicin against oxidative stress, inflammation, and endothelial dysfunction in hy...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/cjpp-2015-0267
更新日期：2016-02-01 00:00:00
abstract：:In this article we comment on the various in vitro biochemical measurements employed to assess the thermogenic activity and capacity of brown adipose tissue. The meaning and significance of changes in tissue weight, protein content, cell number, and mitochondrial mass are each summarized. In addition, various indices ...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章,评审
doi：10.1139/y89-128
更新日期：1989-08-01 00:00:00
abstract：:The present paper reviews current knowledge of the development and plasticity of the inhibitory gamma-aminobutyric acid (GABA) containing circuitry of the cerebral neocortex, in particular, the rat somatosensory barrel field cortex. Recent studies reveal a delayed and protracted maturation of the inhibitory compared w...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章,评审
doi：
更新日期：1997-05-01 00:00:00
abstract：:The effects of a vasopressin (AVP) pressor antagonist, d(CH2)5Tyr(Me)AVP, on mean arterial pressure (MAP), total peripheral resistance (TPR), cardiac output (CO), and the distribution of CO were investigated by the microsphere technique in three groups of pentobarbital anesthetized rats: intact (I), saralasin pretreat...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y86-194
更新日期：1986-08-01 00:00:00
abstract：:Complexes of vanadyl(IV) with 4 monosaccharides and 5 disaccharides were tested in 2 osteoblast-like cell lines (MC3T3E1 and UMR106). Many complexes caused stimulation of UMR106 proliferation (120% basal) in the range of 2.5 to 25 micromol/L. In the nontransformed osteoblasts, some vanadyl-saccharide complexes stimula...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y06-021
更新日期：2006-07-01 00:00:00
abstract：:The administration of small doses of somatostatin (SRIF) (0.01 and 0.1 microgram) into the neostriatal complex of unrestrained, freely moving rats induced general behavioral excitation associated with a variety of stereotyped movements, tremors, and a reduction of rapid eye movements (REM) and deep slow wave sleep (SW...
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
abstract：:It has been proposed that the adult castrated male rat may be used as a model of human postmenopausal osteoporosis. If such a model is valid then the total body calcium of castrated rats should progressively decrease compared with normal rats. To search for this age-related difference, it will be necessary to use a me...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y85-207
更新日期：1985-10-01 00:00:00
abstract：:The effects of atorvastatin and carboxymethylated β-glucan (CMG) on the lipoprotein-cholesterol (LP-C) and lipoprotein-triglyceride (LP-TG) fractions and subfractions at the early stage of murine hyperlipidemia, and its pleiotropic anti-inflammatory effects, were studied. Atorvastatin and CMG were administered in ICR ...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y11-118
更新日期：2012-02-01 00:00:00
abstract：:Several experimental data document an activation of the mitogen-activated protein kinases Erk1 and Erk2 by bradykinin (BK), an agonist of the kinin B2 receptor (B2R). In contrast, other reports showed an inhibitory modulation of mitogenesis by BK. Therefore, we explored in the isolated glomeruli the effect of B2R acti...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y02-033
更新日期：2002-04-01 00:00:00
abstract：:In the present study we have compared the effect of intravenous infusion of a calcium channel blocker, nifedipine (1.0 micrograms.kg-1.min-1 for 20 min), with that of isoproterenol (0.1 micrograms.kg-1.min-1 for 20 min) on the hemodynamic parameters and the vascular response of different locations and tissue layers of...
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 influences of hypertension and hypothyroidism on diabetic cardiomyopathy are not clear. We studied this problem further by characterizing the effects of chronic triiodothyronine (T3) treatment on cardiac performance of diabetic renovascular hypertensive (RVH) rats. Hypertension was effected by clipping the left re...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y91-053
更新日期：1991-03-01 00:00:00
abstract：:The development of the febrile response to E. coli lipopolysaccharide (1.5 micrograms/kg, i.v.) in thyroid-deficient rabbits has been studied. Twenty-eight New Zealand White rabbits weighing 2.1-2.3 kg were used. Hypothyroidism was induced by treatment with propylthiouracil (100 or 200 mg/kg body wt./15 days). Thyroid...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y87-209
更新日期：1987-06-01 00:00:00
abstract：:Impaired nitric oxide (NO) activity is associated with an increase in blood pressure in rats. Voltage-regulated calcium channels are believed to participate in this hemodynamic event. To further test this hypothesis, we examined the effect of nimodipine and verapamil (calcium antagonists) on the pressor activity of di...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/cjpp-76-10-11-983
更新日期：1998-10-01 00:00:00
abstract：:This study was conducted to examine the protective role of crude polysaccharide from brown seaweed Sargassum polycystum against acetaminophen-induced abnormality in blood glucose, serum albumin/globulin ratio, and liver glycogen, lactate, and pyruvate. Liver and renal tissue histology was performed to confirm the effi...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y08-072
更新日期：2008-10-01 00:00:00
abstract：:The validity of a Hodgkin-Huxley type voltage-dependent inactivation of slow inward Ca current (Isi) was tested in frog heart using a computer simulation. The time course of Isi was calculated during the development of a frog atrial action potential (AP). With a time constant of inactivation (tauf) of 55 ms at a membr...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y82-172
更新日期：1982-09-01 00:00:00
abstract：:This study investigated the potential of shikonin as an anticancer agent against liver cancer and an in vitro human hepatoma cancer model system. The HepG2 cell line was the hepatoma cancer model in the present study. The inhibitory effect of shikonin on the growth of HepG2 cells was measured by MTT assay. To explore ...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/Y10-085
更新日期：2010-12-01 00:00:00
abstract：:The kinetics of sodium gradient dependent phosphate uptake by the renal brush border membrane vesicles of the rat have ben studied under various conditions of temperature and pH. From 7 to 30 degrees C the Lineweaver-Burk plots are linear, and the apparent Km progressively increases from 54 to 91 microM. Above 30 degr...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y84-034
更新日期：1984-02-01 00:00:00
abstract：:Radioactively labelled microspheres (15 micron diameter) were used to measure cardiac output (CO) distribution and blood flows in spleen, kidneys, and skeletal muscle before and after normovolemic anemia or polycythemia in anesthetized rats. Hematocrits were changed from 45 to 33% or from 45 to 59% by an exchange tran...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y80-069
更新日期：1980-04-01 00:00:00
abstract：:When isolated rat adipocytes were incubated with increasing concentrations of levamisole (0.5-5 mM), basal glucose oxidation decreased by almost 50% and insulin-stimulated glucose oxidation decreased by 90%. The decrease in glucose oxidation correlated with an inhibition of glucose transport, since levamisole at 5.0 m...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y92-165
更新日期：1992-08-01 00:00:00
abstract：:In rats anesthetized with alpha-chloralose, doses of 0.1, 0.5, and 1 g/kg of ethanol produced an upward shift of baroreflex curves constructed by plotting the heart rate response against mean arterial pressure following evoked rises in mean arterial pressures by phenylephrine or angiotensin II. Whereas the upward shif...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y87-134
更新日期：1987-05-01 00:00:00
abstract：:Patients with Crohn's disease (CD) have higher risk for osteoporosis following decreased level of osteocalcin. We hypothesize that active inflammation following Mycobacterium avium subsp. paratuberculosis (MAP) infection results in elevation of undercarboxylated osteocalcin (ucOC) and downregulation of active osteocal...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/cjpp-2017-0700
更新日期：2018-07-01 00:00:00
abstract：:We investigated potential sex differences in bone resorption and the conservation of whole body bone mass in 24-week-old Sprague-Dawley rats maintained on a 1.0% calcium diet and then fed diets containing 0.02, 0.5, 1.0, or 1.75% calcium for 31 days. Lowering dietary calcium from 1.00% to 0.02% doubled whole skeleton ...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：
更新日期：2001-05-01 00:00:00
abstract：:Transcranial magnetic stimulation over the motor cortex was used to construct a map of the effective sites on the scalp from which short-latency electromyogram responses could be evoked in muscles proximal to either an amputation stump (two subjects) or an ischemically anesthetized forearm (two subjects). At rest, the...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y95-032
更新日期：1995-02-01 00:00:00
abstract：:Noradrenaline spillover from skeletal muscle vascular areas increases during exercise but the underlying mechanisms are not well understood. Muscle contraction itself causes changes in many factors that could affect noradrenaline spillover. For instance, it has been reported that bradykinin is synthesized in skeletal ...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：
更新日期：2001-10-01 00:00:00
abstract：:The effects of L-641,953 (R-8-fluoro-dibenzo[b, f]thiepin-3-carboxylic acid-5-oxide) have been studied on pulmonary and other smooth muscle preparations in vitro and in vivo. When studied in vitro on guinea-pig tracheal chains, L-641,933 produced significant shifts in the dose-response curves to the prostaglandin endo...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y87-087
更新日期：1987-04-01 00:00:00
abstract：:Liver diseases are associated with a decrease in hepatic drug elimination, but there is evidence that cirrhosis does not result in uniform changes of cytochrome P450 (CYP) isoenzymes. The objective of this study was to determine the content and activity of four CYP isoenzymes in the bile duct ligation and carbon tetra...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：
更新日期：2000-11-01 00:00:00
abstract：:An investigation was made of the radiosensitivity of the toxic and immunological properties of Androctonus australis hector venom. This venom was irradiated with two doses of gamma rays (1 and 2 kGy) from a 60Co source. The results showed that venom toxicity was abolished for the two radiation doses (1 and 2 kGy) with...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y03-115
更新日期：2003-12-01 00:00:00
abstract：:We tested the hypothesis that ethanol consumption would aggravate the renal damage induced by cyclophosphamide (CYP). Male C57BL/6J mice from control (n=8) and CYP (n=12) groups had free access to filtered water and standard rodent chow for 12 weeks. Then, 24 h before euthanasia mice received an intraperitoneal inject...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/cjpp-2020-0246
更新日期：2020-11-11 00:00:00
abstract：:The present study was designed to examine the possible neuroprotective and antiepileptic effects of metformin (Metf) in a rat model of pentylenetetrazole (PTZ)-induced epilepsy and its possible underlying mechanisms. Forty male albino rats were assigned to 4 groups of equal size: (1) normal control (NC) group, (2) Met...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/cjpp-2018-0266
更新日期：2019-01-01 00:00:00
