Novel Nitric Oxide Synthase–Dependent Mechanism of Vasorelaxation in Small Arteries From Hypertensive Rats

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Abstract
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 2+ -activated K + channels had no effect on ANG versus blunting relaxation in NORM (log EC 50 : −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 H 2 O 2 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 H 2 O 2 production (ACh: 2.8±0.2 μmol/mg; N ω -nitro- l -arginine methyl ester hydrochloride+ACh: 1.8±0.1 μmol/mg) in small arteries from ANG. H 2 O 2 induced vasorelaxation and catalase blunted ACh-mediated vasorelaxation. In conclusion, Ca 2+ -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 H 2 O 2 production.

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