TY - JOUR
T1 - Novel nitric oxide synthase-dependent mechanism of vasorelaxation in small arteries from hypertensive rats
AU - Kang, Kyu Tae
AU - Sullivan, Jennifer C.
AU - Sasser, Jennifer M.
AU - Imig, John D.
AU - Pollock, Jennifer S.
PY - 2007/4
Y1 - 2007/4
N2 - To determine the mechanism(s) involved in vasorelaxation of small arteries from hypertensive rats, normotensive (NORM), angiotensin II-infused (ANG), high-salt (HS), ANG high-salt (ANG/HS), placebo, and deoxycorticosterone acetate-salt rats were studied. Third-order mesenteric arteries from ANG or ANG/HS displayed decreased sensitivity to acetylcholine (ACh)-induced vasorelaxation compared with NORM or HS, respectively. Maximal relaxations were comparable between groups. Blockade of Ca-activated K channels had no effect on ANG versus blunting relaxation in NORM (log EC50: -6.8±0.1 versus -7.2±0.1 mol/L). NO synthase (NOS) inhibition abolished ACh-mediated relaxation in small arteries from ANG, ANG/HS, and deoxycorticosterone acetate-salt versus blunting relaxation in NORM, HS, and placebo (% maximal relaxation: ANG: 2.7±1.8; ANG/HS: 7.2±3.2; NORM: 91±3.1; HS: 82.1±13.3; deoxycorticosterone acetate-salt: 35.2±17.7; placebo: 79.3±10.3), indicating that NOS is the primary vasorelaxation pathway in these arteries from hypertensive rats. We hypothesized that NO/cGMP signaling and NOS-dependent H2O2 maintains vasorelaxation in small arteries from ANG. ACh increased NOS-dependent cGMP production, indicating that NO/cGMP signaling is present in small arteries from ANG (55.7±6.9 versus 30.5±5.1 pmol/mg), and ACh stimulated NOS-dependent H2O2 production (ACh: 2.8±0.2 μmol/mg; Nω-nitro-L-arginine methyl ester hydrochloride+ACh: 1.8±0.1 μmol/mg) in small arteries from ANG. H2O2 induced vasorelaxation and catalase blunted ACh-mediated vasorelaxation. In conclusion, Ca-activated K channel-mediated relaxation is dysfunctional in small mesenteric arteries from hypertensive rats, and the NOS pathway compensates to maintain vasorelaxation in these arteries through NOS-mediated cGMP and H2O2 production.
AB - To determine the mechanism(s) involved in vasorelaxation of small arteries from hypertensive rats, normotensive (NORM), angiotensin II-infused (ANG), high-salt (HS), ANG high-salt (ANG/HS), placebo, and deoxycorticosterone acetate-salt rats were studied. Third-order mesenteric arteries from ANG or ANG/HS displayed decreased sensitivity to acetylcholine (ACh)-induced vasorelaxation compared with NORM or HS, respectively. Maximal relaxations were comparable between groups. Blockade of Ca-activated K channels had no effect on ANG versus blunting relaxation in NORM (log EC50: -6.8±0.1 versus -7.2±0.1 mol/L). NO synthase (NOS) inhibition abolished ACh-mediated relaxation in small arteries from ANG, ANG/HS, and deoxycorticosterone acetate-salt versus blunting relaxation in NORM, HS, and placebo (% maximal relaxation: ANG: 2.7±1.8; ANG/HS: 7.2±3.2; NORM: 91±3.1; HS: 82.1±13.3; deoxycorticosterone acetate-salt: 35.2±17.7; placebo: 79.3±10.3), indicating that NOS is the primary vasorelaxation pathway in these arteries from hypertensive rats. We hypothesized that NO/cGMP signaling and NOS-dependent H2O2 maintains vasorelaxation in small arteries from ANG. ACh increased NOS-dependent cGMP production, indicating that NO/cGMP signaling is present in small arteries from ANG (55.7±6.9 versus 30.5±5.1 pmol/mg), and ACh stimulated NOS-dependent H2O2 production (ACh: 2.8±0.2 μmol/mg; Nω-nitro-L-arginine methyl ester hydrochloride+ACh: 1.8±0.1 μmol/mg) in small arteries from ANG. H2O2 induced vasorelaxation and catalase blunted ACh-mediated vasorelaxation. In conclusion, Ca-activated K channel-mediated relaxation is dysfunctional in small mesenteric arteries from hypertensive rats, and the NOS pathway compensates to maintain vasorelaxation in these arteries through NOS-mediated cGMP and H2O2 production.
KW - Aorta
KW - Endothelium-dependent vasorelaxation
KW - Hydrogen peroxide
KW - Hypertension
KW - Mesenteric arteries
KW - NO
UR - http://www.scopus.com/inward/record.url?scp=34047218002&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34047218002&partnerID=8YFLogxK
U2 - 10.1161/01.HYP.0000259669.40991.1e
DO - 10.1161/01.HYP.0000259669.40991.1e
M3 - Article
C2 - 17309950
AN - SCOPUS:34047218002
SN - 0194-911X
VL - 49
SP - 893
EP - 901
JO - Hypertension
JF - Hypertension
IS - 4
ER -