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(Circulation. 1999;100:1680-1683.)
© 1999 American Heart Association, Inc.

Brief Rapid Communication

Vasoconstriction to Endogenous Endothelin-1 Is Increased in the Peripheral Circulation of Patients With Essential Hypertension

Stefano Taddei, MD; Agostino Virdis, MD; Lorenzo Ghiadoni, MD; Isabella Sudano, MD; Massimo Notari, MD; Antonio Salvetti, MD

From the Department of Internal Medicine, University of Pisa (S.T., A.V., L.G., I.S., A.S.), Pisa, Italy, and TAKEDA Italia Farmaceutici SpA (M.N.), Rome, Italy.

Correspondence to Stefano Taddei, MD, Department of Internal Medicine, University of Pisa, Via Roma, 67, 56100 Pisa, Italy. E-mail s.taddei{at}int.med.unipi.it

Background—In humans, endothelin (ET)-1 could be implicated in the pathophysiology of several cardiovascular diseases, including essential hypertension. We therefore evaluated the role of ET-1 in control of vascular tone in essential hypertension.

Methods and Results—We used strain-gauge venous plethysmography to test changes in forearm blood flow induced by intrabrachial infusion of TAK-044 (10, 30, and 100 µg · 100 mL^-1 · min^-1), an ET_A/ET_B receptor antagonist, or sodium nitroprusside (1 and 2 µg · 100 mL^-1 · min^-1), a vasodilator that acts on smooth muscle cells, in hypertensive patients and healthy controls (n=10 in each group). The NO pathway was also evaluated by infusion of N^G-monomethyl-L-arginine, (L-NMMA; 10, 30, and 100 µg · 100 mL^-1 · min^-1), an NO synthase inhibitor, and norepinephrine (3, 9, and 30 ng · 100 mL^-1 · min^-1) as control. Immunoreactive plasma ET-1 was measured by radioimmunoassay. In hypertensive patients, TAK-044 caused a vasodilation that was significantly (P<0.01) increased compared with normotensive subjects. Moreover, vasoconstriction to L-NMMA was significantly (P<0.01) decreased in hypertensive patients compared with controls. In contrast, the vascular responses to sodium nitroprusside and norepinephrine, as well as levels of immunoreactive plasma ET-1, were similar in hypertensive patients and controls. In the study population, vasodilation to TAK-044 and vasoconstriction to L-NMMA showed an inverse correlation (r=-0.56, P<0.05).

Conclusions—These results indicate that TAK-044 caused a greater degree of vasodilation in the forearm vessels of essential hypertensive patients compared with normotensive subjects, an alteration associated with decreased tonic NO release.

Key Words: vasodilation • hypertension • nitric oxide • endothelin

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