TY - JOUR
T1 - Modulation by salt intake of the vascular response mediated through adenosine A2A receptor
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, J R
PY - 2010/7
Y1 - 2010/7
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
UR - http://www.scopus.com/inward/record.url?scp=77954414532&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77954414532&partnerID=8YFLogxK
U2 - 10.1152/ajpregu.00823.2009
DO - 10.1152/ajpregu.00823.2009
M3 - Article
C2 - 20427718
AN - SCOPUS:77954414532
SN - 0363-6119
VL - 299
SP - R325-R333
JO - American Journal of Physiology - Regulatory Integrative and Comparative Physiology
JF - American Journal of Physiology - Regulatory Integrative and Comparative Physiology
IS - 1
ER -