Article

High-salt diet enhances mouse aortic relaxation through adenosine A2A receptor via CYP epoxygenases.

Dept. of Physiology and Pharmacology, Center for Interdisciplinary Research in Cardiovascular Sciences, Health Science Center-North, 1 Morgantown, WV 26506, USA.
AJP Regulatory Integrative and Comparative Physiology (impact factor: 3.34). 12/2008; 296(3):R567-74. DOI:10.1152/ajpregu.90798.2008 pp.R567-74
Source: PubMed

ABSTRACT We hypothesize that A(2A) adenosine receptors (A(2A) AR) promote aortic relaxation in mice through cytochrome P450 (CYP)-epoxygenases and help to avoid salt sensitivity. Aortas from male mice maintained on a high-salt (HS; 7% NaCl) or normal-salt (NS; 0.45% NaCl) diet for 4-5 wks were used. Concentration-response curves (10(-11)-10(-5) M) for 5'-N-ethylcarboxamidoadenosine (NECA; a nonselective adenosine analog) and CGS 21680 (A(2A) AR agonist) were obtained with different antagonists including ZM 241385 (A(2A) AR antagonist; 10(-6) M), SCH 58261 (A(2A) AR antagonist; 10(-6) M), N(omega)-nitro-l-arginine methyl ester (l-NAME; endothelial nitric oxide synthase inhibitor; 10(-4) M) and inhibitors including methylsulfonyl-propargyloxyphenylhexanamide (MS-PPOH; CYP epoxygenases inhibitor; 10(-5)M), 14,15-epoxyeicosa-5(z)-enoic acid (14,15-EEZE; EET antagonist; 10(-5)M), dibromo-dodecenyl-methylsulfimide (DDMS; CYP4A inhibitor; 10(-5)M), and HET0016 (20-HETE inhibitor; 10(-5)M). At 10(-7) M of NECA, significant relaxation in HS (+22.58 +/- 3.12%) was observed compared with contraction in NS (-10.62 +/- 6.27%, P < 0.05). ZM 241385 changed the NECA response to contraction (P < 0.05) in HS. At 10(-7) M of CGS 21680, significant relaxation in HS (+32.04 +/- 3.08%) was observed compared with NS (+10.45 +/- 1.34%, P < 0.05). SCH 58261, l-NAME, MS-PPOH, and 14,15-EEZE changed the CGS 21680-induced relaxation to contraction (P < 0.05) in HS. Interestingly, DDMS and HET0016 changed CGS 21680 response to relaxation (P < 0.05) in NS; however, there was no significant difference found between DDMS, HET0016-treated HS and NS vs. nontreated HS group (P > 0.05). CYP2C29 protein was 55% and 74% upregulated in HS vs. NS (P < 0.05) mice aorta and kidney, respectively. CYP4A protein was 30.30% and 35.70% upregulated in NS vs. HS (P < 0.05) mice aorta and kidneys, respectively. A(1) AR was downregulated, whereas A(2A) AR was upregulated in HS compared with NS. These data suggest that HS may activate CYP2C29 via A(2A) AR, causing relaxation, whereas NS may contribute to the upregulation of CYP4A causing contraction.

0 0
 · 
0 Bookmarks
 · 
31 Views
  • Article: Technical review and considerations for a cerebrospinal fluid leakage study.
    Vesper V Grantham, Brian Blakley, Jan Winn
    [show abstract] [hide abstract]
    ABSTRACT: Within the past decade, published diagnostic algorithms for cerebrospinal fluid (CSF) leakage have included beta-2-transferrin analysis, rigid nasal endoscopy, high-resolution CT, CT cisternography, CT fluorescein lumbar puncture, and MRI but have not included the nuclear medicine CSF leakage study. However, some physicians still use this study today. This case report reviews the procedure and data calculations for the study. The presented case demonstrates how patient ingenuity in maintaining a compromised pledget for counting after sneezing contributed to the final diagnostic outcome. The patient was a 58-y-old man who presented with persistent nasal drainage and headaches, with no history of previous head trauma or surgery. The patient was referred to the nuclear medicine department for a CSF leakage study, which had positive findings and led to a final diagnosis of a large dural and skull defect posteriorly over the ethmoid sinuses.
    Journal of Nuclear Medicine Technology 04/2006; 34(1):48-51.
  • Article: Cytochrome P450 2C is an EDHF synthase in coronary arteries.
    B Fisslthaler, R Popp, L Kiss, M Potente, D R Harder, I Fleming, R Busse
    [show abstract] [hide abstract]
    ABSTRACT: In most arterial beds a significant endothelium-dependent dilation to various stimuli persists even after inhibition of nitric oxide synthase and cyclo-oxygenase. This dilator response is preceded by an endothelium-dependent hyperpolarization of vascular smooth muscle cells, which is sensitive to a combination of the calcium-dependent potassium-channel inhibitors charybdotoxin and apamin, and is assumed to be mediated by an unidentified endothelium-derived hyperpolarizing factor (EDHF). Here we show that the induction of cytochrome P450 (CYP) 2C8/34 in native porcine coronary artery endothelial cells by beta-naphthoflavone enhances the formation of 11,12-epoxyeicosatrienoic acid, as well as EDHF-mediated hyperpolarization and relaxation. Transfection of coronary arteries with CYP 2C8/34 antisense oligonucleotides results in decreased levels of CYP 2C and attenuates EDHF-mediated vascular responses. Thus, a CYP-epoxygenase product is an essential component of EDHF-mediated relaxation in the porcine coronary artery, and CYP 2C8/34 fulfils the criteria for the coronary EDHF synthase.
    Nature 10/1999; 401(6752):493-7. · 36.28 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

14,15-epoxyeicosa-5(z)-enoic acid
 
aortic relaxation
 
CGS 21680-induced relaxation
 
Concentration-response curves
 
CYP epoxygenases inhibitor
 
CYP)-epoxygenases
 
CYP4A
 
CYP4A inhibitor
 
CYP4A protein
 
cytochrome P450
 
EET antagonist
 
endothelial nitric oxide synthase inhibitor
 
HET0016-treated HS
 
male mice
 
N(omega)-nitro-l-arginine methyl ester
 
nonselective adenosine analog
 
nontreated HS group
 
normal-salt
 
salt sensitivity
 
significant relaxation