title: Role of endothelin in the pathogenesis of hypertension.
abstract: In 1985, investigators characterized a potent vasoconstrictor of endothelial origin called endothelin (ET). Subsequently, 3 peptides were recognized that had a comparable molecular structure but different receptors that mediate potent vasoconstrictive and mild vasodilative effects. The renal effects are characterized by natriuresis despite renal vasoconstriction. This effect, along with the stimulation of ET by high sodium intake, suggests that ET may be responsible for maintaining sodium balance when the renin-angiotensin system is depressed. Endothelin is activated in desoxycorticosterone acetate salt hypertension models and salt-sensitive hypertension. However, ET involvement with spontaneous hypertension models and renovascular hypertension in rats appears minimal. In humans, the role of ET appears similar to that in experimental animals; in both, ET regulates salt metabolism. Salt-sensitive patients exhibit a blunted renal ET-1 response during sodium load. The role of ET in humans has been investigated using nonspecific ET receptor blockers that inhibit the vasoconstrictive and vasodilative components of ET. However, the effects of ET blockade should be investigated with ET subtype A receptor blockers that mediate vasoconstriction alone. Effects of ET blockade also should be evaluated with respect to stimulation of oxidative stress and tissue damage, important mechanisms responsible for tissue fibrosis. This review offers the clinician a balanced view on the hypertensive mechanisms involved with activation of ET and associated clinical implications.
authors.affiliation: Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, Minn 55905, USA.
authors.forename: Candelas
authors.initials: C
authors.lastname: Perez del Villar
authors.forename: Carlos Javier
authors.initials: CJ
authors.lastname: Garcia Alonso
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Feldstein
authors.forename: Luis A
authors.initials: LA
authors.lastname: Juncos
authors.forename: J Carlos
authors.initials: JC
authors.lastname: Romero
mesh_terms: D000818:Animals; D002320:Cardiovascular Physiological Phenomena; D004195:Disease Models, Animal; D016232:Endothelins / Q000502:physiology*; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000209:etiology*; D007668:Kidney / Q000502:physiology; D051381:Rats; D012964:Sodium / Q000378:metabolism
chemical_list: D016232:Endothelins; D012964:Sodium