Endothelin: Role in experimental hypertension

The role of endothelins (ET) in blood pressure elevation remains controvers ial. Data supporting involvement of the ET system in different forms of gen etic and experimental hypertension in the rat has appeared in the literatur e in recent years. Production of endothelin (ET)-1 may be enhanced in sever al experimental rat models of hypertension. Examples of these exhibiting in creased preproendothelin-1 mRNA or peptide in the vasculature include salt- sensitive forms Like deoxycorticosterone (DOCA)-salt hypertension, DOCA-sal t treated spontaneously hypertensive rat (SHR) and Dahl salt-sensitive rats , and other models like stroke-prone SHR, angiotensin II-infused rats and f ructose-fed rats, and possibly 1-kidney 1 clip (1-K 1C) Goldblatt hypertens ive rats. SHR, 2-kidney 1 clip (2-K 1C) Goldblatt hypertensive rats and chr onic N-omega-nitro-L-arginine methyl ester (L-NAME)-treated hypertensive ra ts do not appear to exhibit an ET-1 component. Significant vascular growth, and a hypotensive response and regression of vascular growth after treatme nt with an ET antagonist demonstrate the endothelin-dependency present in s ome hypertensive models. Severity of high blood pressure elevation, salt-se nsitivity and insulin resistance may be common denominators of involvement of the ET system in hypertension. ET antagonism in hypertension may result in regression of vascular damage, prevention of stroke and renal failure an d improvement of heart failure. Whether the same is true in human hypertens ion remains to be established.