title: Vasoconstriction to endogenous endothelin-1 is increased in the peripheral circulation of patients with essential hypertension.
abstract: 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.
  
  
  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.
authors.affiliation: Department of Internal Medicine, University of Pisa, Pisa, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Taddei
authors.forename: A
authors.initials: A
authors.lastname: Virdis
authors.forename: L
authors.initials: L
authors.lastname: Ghiadoni
authors.forename: I
authors.initials: I
authors.lastname: Sudano
authors.forename: M
authors.initials: M
authors.lastname: Notari
authors.forename: A
authors.initials: A
authors.lastname: Salvetti
mesh_terms: D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000097:blood*; D005542:Forearm / Q000098:blood supply; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000503:physiopathology*; D007261:Infusions, Intra-Arterial; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000008:administration & dosage / Q000494:pharmacology*; D009638:Norepinephrine / Q000008:administration & dosage / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000494:pharmacology*; D010991:Plethysmography; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology*; D019323:omega-N-Methylarginine / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D010456:Peptides, Cyclic; D014665:Vasodilator Agents; C088196:TAK 044; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D019001:Nitric Oxide Synthase; D009638:Norepinephrine