Document Detail

Vasoconstriction to endogenous endothelin-1 is increased in the peripheral circulation of patients with essential hypertension.
MedLine Citation:
PMID:  10525485     Owner:  NLM     Status:  MEDLINE    
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 microgram. 100 mL(-1). min(-1)), an ET(A)/ET(B) receptor antagonist, or sodium nitroprusside (1 and 2 microgram. 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 microgram. 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.
S Taddei; A Virdis; L Ghiadoni; I Sudano; M Notari; A Salvetti
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Circulation     Volume:  100     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  1999 Oct 
Date Detail:
Created Date:  1999-11-23     Completed Date:  1999-11-23     Revised Date:  2005-11-17    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1680-3     Citation Subset:  AIM; IM    
Department of Internal Medicine, University of Pisa, Pisa, Italy.
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MeSH Terms
Endothelin-1 / blood*
Forearm / blood supply
Hypertension / blood,  physiopathology*
Infusions, Intra-Arterial
Middle Aged
Nitric Oxide Synthase / antagonists & inhibitors
Nitroprusside / administration & dosage,  pharmacology*
Norepinephrine / administration & dosage,  pharmacology
Peptides, Cyclic / administration & dosage,  pharmacology*
Receptors, Endothelin / antagonists & inhibitors*
Reference Values
Regional Blood Flow / drug effects*
Vasoconstriction / drug effects*,  physiology
Vasodilator Agents / pharmacology*
omega-N-Methylarginine / administration & dosage,  pharmacology*
Reg. No./Substance:
0/Endothelin-1; 0/Peptides, Cyclic; 0/Receptors, Endothelin; 0/Vasodilator Agents; 15078-28-1/Nitroprusside; 157380-72-8/TAK 044; 17035-90-4/omega-N-Methylarginine; 51-41-2/Norepinephrine; EC Oxide Synthase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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