Modulation by salt intake of the vascular response mediated through adenosine A2A receptor: Role of CYP epoxygenase and soluble epoxide hydrolase

Mohammed A. Nayeem, Darryl C. Zeldin, Matthew A. Boegehold, Christophe Morisseau, Anne Marowsky, Dovenia S. Ponnoth, Kevin P. Roush, John R. Falck

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

High-salt intake can change the effect of adenosine on arterial tone in mice. The aim of this study was to clarify the mechanism by which this occurs. Using aortas from mice fed a 4% NaCl (HS) or 0.45% NaCl (NS) diet for 4-5 wks, concentration-response curves for ACh, 5′-N-ethylcarboxamidoadenosine (NECA; adenosine analog) and 2-p-(2-carboxyethyl)phenethylamino-5′-N- ethylcarboxamidoadenosine hydrochloride hydrate [CGS-21680; A2A adenosine receptor (A2A AR) agonist] were obtained with N ω-nitro-L-arginine methyl ester (L-NAME; nitric oxide inhibitor, 10-4 M), methylsulfonyl-propargyloxyphenylhexanamide [MS-PPOH; a CYP (cytochrome P-450) epoxygenase blocker, 10 -5 M including CYP2J2], 12-(3-adamantan-1-yl-ureido)dodecanoic acid [AUDA; soluble epoxide hydrolase (sEH) blocker, 10-5 M], dibromo- dodecenylmethylsulfimide [DDMS; CYP ω-hydroxylase (CYP4A blocker), 10 -5 M], glibenclamide (KATP channel blocker; 10 -5 M) and 5-hydroxydecanoate (5-HD; mitochondrial-KATP channel blocker, 10-4 M). HS dose response to ACh (10-7 - 10-5 M) was not different from NS (P > 0.05). Relaxation to 10-6 M NECA was greater in the HS group (28.4 ± 3.9%) than in the NS group (4.1 ± 2.3%). Relaxation to 10-6 M CGS-21680 was also greater in HS (27.9 ±4.5%) than in NS (4.9 ± 2.2%). L-NAME was able to block the dose response of ACh (10-7 - 10-5 M) equally in both HS and NS (P > 0.05), whereas L-NAME did not block CGS-21680-induced response in HS. In HS the CGS-21680 response was greatly reduced by MS-PPOH (to 4.7 ± 2.0%) and 5-HD (to 8.9 ± 2.2%), and also abolished by glibenclamide (-1.0 ± 5.9%). In NS, the CGS-21680 response was increased by AUDA (to 26.3 ± 3.4%) and DDMS (to 27.2 ± 3.0%). Compared with NS, HS vessels showed increased CYP2J2 and A 2A AR expression (46 and 74% higher, respectively) but decreased sEH, CYP4A, and A1 AR expression (75, 30, and 55% lower, respectively). These data suggest that in mice fed NScontaining diet, upregulation of arterial A1 receptor causes vasoconstriction via increased sEH and CYP4A proteins. However, in mice fed HS-containing diet, upregulation of A 2A receptor protein triggers vascular relaxation through ATP-sensitive (K+) channels via upregulation of CYP2J2 enzyme.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume299
Issue number1
DOIs
StatePublished - Jul 2010

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Adenosine A2A Receptors
Epoxide Hydrolases
Cytochrome P-450 Enzyme System
Blood Vessels
Cytochrome P-450 CYP4A
Salts
Adenosine-5'-(N-ethylcarboxamide)
NG-Nitroarginine Methyl Ester
Up-Regulation
Glyburide
Diet
Adenosine
Adenosine A2 Receptor Agonists
KATP Channels
Mixed Function Oxygenases
Vasoconstriction
Aorta
2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine
Nitric Oxide
Proteins

Keywords

  • Adenosine
  • Contraction
  • K channels
  • Relaxation

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Modulation by salt intake of the vascular response mediated through adenosine A2A receptor : Role of CYP epoxygenase and soluble epoxide hydrolase. / Nayeem, Mohammed A.; Zeldin, Darryl C.; Boegehold, Matthew A.; Morisseau, Christophe; Marowsky, Anne; Ponnoth, Dovenia S.; Roush, Kevin P.; Falck, John R.

In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 299, No. 1, 07.2010.

Research output: Contribution to journalArticle

Nayeem, Mohammed A. ; Zeldin, Darryl C. ; Boegehold, Matthew A. ; Morisseau, Christophe ; Marowsky, Anne ; Ponnoth, Dovenia S. ; Roush, Kevin P. ; Falck, John R. / Modulation by salt intake of the vascular response mediated through adenosine A2A receptor : Role of CYP epoxygenase and soluble epoxide hydrolase. In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology. 2010 ; Vol. 299, No. 1.
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abstract = "High-salt intake can change the effect of adenosine on arterial tone in mice. The aim of this study was to clarify the mechanism by which this occurs. Using aortas from mice fed a 4{\%} NaCl (HS) or 0.45{\%} NaCl (NS) diet for 4-5 wks, concentration-response curves for ACh, 5′-N-ethylcarboxamidoadenosine (NECA; adenosine analog) and 2-p-(2-carboxyethyl)phenethylamino-5′-N- ethylcarboxamidoadenosine hydrochloride hydrate [CGS-21680; A2A adenosine receptor (A2A AR) agonist] were obtained with N ω-nitro-L-arginine methyl ester (L-NAME; nitric oxide inhibitor, 10-4 M), methylsulfonyl-propargyloxyphenylhexanamide [MS-PPOH; a CYP (cytochrome P-450) epoxygenase blocker, 10 -5 M including CYP2J2], 12-(3-adamantan-1-yl-ureido)dodecanoic acid [AUDA; soluble epoxide hydrolase (sEH) blocker, 10-5 M], dibromo- dodecenylmethylsulfimide [DDMS; CYP ω-hydroxylase (CYP4A blocker), 10 -5 M], glibenclamide (KATP channel blocker; 10 -5 M) and 5-hydroxydecanoate (5-HD; mitochondrial-KATP channel blocker, 10-4 M). HS dose response to ACh (10-7 - 10-5 M) was not different from NS (P > 0.05). Relaxation to 10-6 M NECA was greater in the HS group (28.4 ± 3.9{\%}) than in the NS group (4.1 ± 2.3{\%}). Relaxation to 10-6 M CGS-21680 was also greater in HS (27.9 ±4.5{\%}) than in NS (4.9 ± 2.2{\%}). L-NAME was able to block the dose response of ACh (10-7 - 10-5 M) equally in both HS and NS (P > 0.05), whereas L-NAME did not block CGS-21680-induced response in HS. In HS the CGS-21680 response was greatly reduced by MS-PPOH (to 4.7 ± 2.0{\%}) and 5-HD (to 8.9 ± 2.2{\%}), and also abolished by glibenclamide (-1.0 ± 5.9{\%}). In NS, the CGS-21680 response was increased by AUDA (to 26.3 ± 3.4{\%}) and DDMS (to 27.2 ± 3.0{\%}). Compared with NS, HS vessels showed increased CYP2J2 and A 2A AR expression (46 and 74{\%} higher, respectively) but decreased sEH, CYP4A, and A1 AR expression (75, 30, and 55{\%} lower, respectively). These data suggest that in mice fed NScontaining diet, upregulation of arterial A1 receptor causes vasoconstriction via increased sEH and CYP4A proteins. However, in mice fed HS-containing diet, upregulation of A 2A receptor protein triggers vascular relaxation through ATP-sensitive (K+) channels via upregulation of CYP2J2 enzyme.",
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T2 - Role of CYP epoxygenase and soluble epoxide hydrolase

AU - Nayeem, Mohammed A.

AU - Zeldin, Darryl C.

AU - Boegehold, Matthew A.

AU - Morisseau, Christophe

AU - Marowsky, Anne

AU - Ponnoth, Dovenia S.

AU - Roush, Kevin P.

AU - Falck, John R.

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N2 - High-salt intake can change the effect of adenosine on arterial tone in mice. The aim of this study was to clarify the mechanism by which this occurs. Using aortas from mice fed a 4% NaCl (HS) or 0.45% NaCl (NS) diet for 4-5 wks, concentration-response curves for ACh, 5′-N-ethylcarboxamidoadenosine (NECA; adenosine analog) and 2-p-(2-carboxyethyl)phenethylamino-5′-N- ethylcarboxamidoadenosine hydrochloride hydrate [CGS-21680; A2A adenosine receptor (A2A AR) agonist] were obtained with N ω-nitro-L-arginine methyl ester (L-NAME; nitric oxide inhibitor, 10-4 M), methylsulfonyl-propargyloxyphenylhexanamide [MS-PPOH; a CYP (cytochrome P-450) epoxygenase blocker, 10 -5 M including CYP2J2], 12-(3-adamantan-1-yl-ureido)dodecanoic acid [AUDA; soluble epoxide hydrolase (sEH) blocker, 10-5 M], dibromo- dodecenylmethylsulfimide [DDMS; CYP ω-hydroxylase (CYP4A blocker), 10 -5 M], glibenclamide (KATP channel blocker; 10 -5 M) and 5-hydroxydecanoate (5-HD; mitochondrial-KATP channel blocker, 10-4 M). HS dose response to ACh (10-7 - 10-5 M) was not different from NS (P > 0.05). Relaxation to 10-6 M NECA was greater in the HS group (28.4 ± 3.9%) than in the NS group (4.1 ± 2.3%). Relaxation to 10-6 M CGS-21680 was also greater in HS (27.9 ±4.5%) than in NS (4.9 ± 2.2%). L-NAME was able to block the dose response of ACh (10-7 - 10-5 M) equally in both HS and NS (P > 0.05), whereas L-NAME did not block CGS-21680-induced response in HS. In HS the CGS-21680 response was greatly reduced by MS-PPOH (to 4.7 ± 2.0%) and 5-HD (to 8.9 ± 2.2%), and also abolished by glibenclamide (-1.0 ± 5.9%). In NS, the CGS-21680 response was increased by AUDA (to 26.3 ± 3.4%) and DDMS (to 27.2 ± 3.0%). Compared with NS, HS vessels showed increased CYP2J2 and A 2A AR expression (46 and 74% higher, respectively) but decreased sEH, CYP4A, and A1 AR expression (75, 30, and 55% lower, respectively). These data suggest that in mice fed NScontaining diet, upregulation of arterial A1 receptor causes vasoconstriction via increased sEH and CYP4A proteins. However, in mice fed HS-containing diet, upregulation of A 2A receptor protein triggers vascular relaxation through ATP-sensitive (K+) channels via upregulation of CYP2J2 enzyme.

AB - High-salt intake can change the effect of adenosine on arterial tone in mice. The aim of this study was to clarify the mechanism by which this occurs. Using aortas from mice fed a 4% NaCl (HS) or 0.45% NaCl (NS) diet for 4-5 wks, concentration-response curves for ACh, 5′-N-ethylcarboxamidoadenosine (NECA; adenosine analog) and 2-p-(2-carboxyethyl)phenethylamino-5′-N- ethylcarboxamidoadenosine hydrochloride hydrate [CGS-21680; A2A adenosine receptor (A2A AR) agonist] were obtained with N ω-nitro-L-arginine methyl ester (L-NAME; nitric oxide inhibitor, 10-4 M), methylsulfonyl-propargyloxyphenylhexanamide [MS-PPOH; a CYP (cytochrome P-450) epoxygenase blocker, 10 -5 M including CYP2J2], 12-(3-adamantan-1-yl-ureido)dodecanoic acid [AUDA; soluble epoxide hydrolase (sEH) blocker, 10-5 M], dibromo- dodecenylmethylsulfimide [DDMS; CYP ω-hydroxylase (CYP4A blocker), 10 -5 M], glibenclamide (KATP channel blocker; 10 -5 M) and 5-hydroxydecanoate (5-HD; mitochondrial-KATP channel blocker, 10-4 M). HS dose response to ACh (10-7 - 10-5 M) was not different from NS (P > 0.05). Relaxation to 10-6 M NECA was greater in the HS group (28.4 ± 3.9%) than in the NS group (4.1 ± 2.3%). Relaxation to 10-6 M CGS-21680 was also greater in HS (27.9 ±4.5%) than in NS (4.9 ± 2.2%). L-NAME was able to block the dose response of ACh (10-7 - 10-5 M) equally in both HS and NS (P > 0.05), whereas L-NAME did not block CGS-21680-induced response in HS. In HS the CGS-21680 response was greatly reduced by MS-PPOH (to 4.7 ± 2.0%) and 5-HD (to 8.9 ± 2.2%), and also abolished by glibenclamide (-1.0 ± 5.9%). In NS, the CGS-21680 response was increased by AUDA (to 26.3 ± 3.4%) and DDMS (to 27.2 ± 3.0%). Compared with NS, HS vessels showed increased CYP2J2 and A 2A AR expression (46 and 74% higher, respectively) but decreased sEH, CYP4A, and A1 AR expression (75, 30, and 55% lower, respectively). These data suggest that in mice fed NScontaining diet, upregulation of arterial A1 receptor causes vasoconstriction via increased sEH and CYP4A proteins. However, in mice fed HS-containing diet, upregulation of A 2A receptor protein triggers vascular relaxation through ATP-sensitive (K+) channels via upregulation of CYP2J2 enzyme.

KW - Adenosine

KW - Contraction

KW - K channels

KW - Relaxation

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