Premium
Role of endothelium‐derived hyperpolarizing factor (EDHF) in hypoxia‐induced vasodilation in humans
Author(s) -
Leuenberger Urs A.,
Spilk Samson,
Yoder Jonathan,
Blaha Cheryl,
Mast Jessica
Publication year - 2010
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.24.1_supplement.1022.6
Subject(s) - vasodilation , endothelium derived hyperpolarizing factor , hypoxia (environmental) , brachial artery , endocrinology , nitric oxide , medicine , pharmacology , anesthesia , chemistry , blood pressure , oxygen , organic chemistry , charybdotoxin
Prior studies suggest that adenosine, nitric oxide and prostaglandins contribute to skeletal muscle vasodilation induced by systemic hypoxia in humans. However, pharmacological blocking studies suggest that other vasodilator systems such as for example endothelium‐derived hyperpolarizing factor (EDHF) may be involved. Fluconazole, an antifungal agent with cytochrome P450 2C9 inhibitor properties can be used to block EDHF. We exposed healthy humans (n=8) to systemic hypoxia (inspired O 2 fraction 0.1 for 10 min; arterial pO 2 ~38 mmHg) and measured forearm blood flow (FBF, plethysmography) during brachial artery infusion of fluconazole (0.33 mg/min) and of fluconazole and N G –monomethyl‐L‐arginine (L‐NMMA; 50 mg) in the infused and opposite forearms. Forearm vascular conductance (FVC) was calculated as FBF/mean blood pressure. During normoxia, fluconazole had no effect on FVC and failed to attenuate the rise in FVC during hypoxia ( P =NS). However, during co‐infusion of fluconazole and L‐NMMA, the hypoxia‐induced increase in FVC was markedly reduced (experimental vs. control: 0.11±0.23 vs. 1.65±0.66 units; P <0.05). Because L‐NMMA induces an experimental NO‐deficient state, these data suggest that EDHF may be uniquely important when bioavailability of NO is diminished. This could have broad implications in conditions characterized by oxidative stress. Supported by NIH P01 HL077670, and M01 RR010732.