October 14, 2003Hypertension63 citationsOpen Access
Role of Endothelium-Derived Hyperpolarizing Factor in Human Forearm Circulation
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Key Result
Tetraethylammonium chloride, an EDHF inhibitor, significantly reduced basal forearm blood flow (P<0.05) and inhibited vasodilation evoked by substance P and bradykinin (P<0.001).
Structured PICO
Does inhibition of endothelium-derived hyperpolarizing factor with tetraethylammonium chloride affect forearm blood flow and vasodilatation in healthy humans?
P
Population
31 healthy, normal subjects (mean+/-SE age, 23+/-2 years; 24 men and 7 women).
I
Intervention
Tetraethylammonium chloride (TEA, 1 mg/min for 20 minutes) infused into the brachial artery, after oral aspirin (486 mg) and NG-monomethyl-L-arginine (8 micromol/min for 5 minutes).
O
Outcome
Forearm blood flow (FBF) measured by strain-gauge plethysmographysurrogate
Endothelium-derived hyperpolarizing factor contributes substantially to basal forearm vascular resistance and vasodilatation evoked by substance P and bradykinin in humans in vivo.
Main Result
p-value: p=<0.05
Abstract
Endothelium-derived hyperpolarizing factor (EDHF) contributes to endothelium-dependent relaxation of isolated arteries, but it is not known whether this also occurs in the case of humans in vivo. The present study examined the role of EDHF in human forearm circulation. Forearm blood flow (FBF) was measured by strain-gauge plethysmography in 31 healthy, normal subjects (mean+/-SE age, 23+/-2 years; 24 men and 7 women). After oral administration of aspirin (486 mg), we infused NG-monomethyl-L-arginine (8 micromol/min for 5 minutes) into the brachial artery. We used tetraethylammonium chloride (TEA, 1 mg/min for 20 minutes), a KCa channel blocker, as an EDHF inhibitor, and nicorandil as a direct K+ channel opener. TEA significantly reduced FBF (P<0.05) but did not change systemic arterial blood pressure. Furthermore, TEA significantly inhibited the FBF increase in response to substance P (0.8, 1.6, 3.2, and 6.4 ng/min, n=8) and bradykinin (12.5, 25, 50, and 100 ng/min, n=8; both P<0.001), whereas it did not affect the FBF increase in response to acetylcholine (4, 8, 16, and 32 microg/min, n=8), sodium nitroprusside (0.4, 0.8, 1.6, and 3.2 microg/min, n=8), or nicorandil (0.128, 0.256, 0.512, and 1.024 mg/min, n=8). These results suggest that EDHF contributes substantially to basal forearm vascular resistance, as well as to forearm vasodilatation evoked by substance P and bradykinin in humans in vivo.