Published Online
on October 13, 2003

A more recent version of this article appeared on November 1, 2003

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Submitted on February 21, 2003
Revised on March 19, 2003

Role of Endothelium-Derived Hyperpolarizing Factor in Human Forearm Circulation

Kosuke Inokuchi; Yoshitaka Hirooka^*; Hiroaki Shimokawa; Koji Sakai; Takuya Kishi; Koji Ito; Yoshikuni Kimura; and Akira Takeshita

From the Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.

^* To whom correspondence should be addressed. E-mail: hyoshi{at}cardiol.med.kyushu-u.ac.jp.

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 N^G-monomethyl-L-arginine (8 µmol/min for 5 minutes) into the brachial artery. We used tetraethylammonium chloride (TEA, 1 mg/min for 20 minutes), a K_Ca 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 µg/min, n=8), sodium nitroprusside (0.4, 0.8, 1.6, and 3.2 µg/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.

Key words: endothelium • vasodilation • nitric oxide • prostaglandins • bradykinin

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