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Upregulation of iNOS contributes to attenuated eNOS‐dependent cutaneous vasodilation in essential hypertensive humans
Author(s) -
Smith Caroline J.,
Bruning Rebecca S.,
Stanhewicz Anna E.,
Holowatz Lacy A.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.821.13
Essential hypertension (HT) is a pro‐inflammatory, pro‐constrictor condition coinciding with endothelial dysfunction and inward vessel remodeling. Our aim was to determine if iNOS upregulation attenuates eNOS‐dependent cutaneous vasodilation (VD) in HT humans. Four microdialysis (MD) fibers were placed in the forearm of 7 hypertensive (106 ± 10 mmHg) and 8 normotensive (NT; 85 ± 8 mmHg) men and women: Ringers (control; C), 0.1 mM 1400W (iNOS inhibited), 5 mM NPLA (nNOS inhibited), 20 mM L‐NAME (non‐selective NOS inhibited). Skin blood flow was measured and cutaneous vascular conductance was calculated (%CVC max ; 28 mM SNP, 43°C) during local heating (42°C) and acetylcholine dose‐response protocols (Ach; 0.01, 0.1, 1, 5, 10, 50, 100 mM). The local heating plateau was attenuated at C (94 ± 4 vs. 72 ± 3 %CVC max , p<0.05) and NPLA sites (97 ± 4 vs. 80 ± 11 %CVC max , p<001) in HT. iNOS inhibition augmented the plateau such that there were no differences between groups at the 1400W (92 ± 3 vs. 90 ± 13 %CVC max ) or L‐NAME sites (50 ± 3 vs. 55 ± 3 %CVC max ). Ach‐induced VD was attenuated at C at all doses ≥ 0.1 mM Ach in HT vs. NT, and was restored with iNOS inhibition (all P<0.01). These data suggest that iNOS inhibition augments eNOS‐dependent cutaneous VD during local heating and Ach dose‐response in essential hypertensive humans. Supported by NIH RO1‐ HL093238 ‐01