Intrarenal endothelin-1 and hypertension

Abstract

Endothelin-1 (ET-1) is a 21-amino acid peptide with an order of magnitude greater vasoconstrictive potency than any known endogenous compound. Since its discovery one decade ago, more than 1,500 publications have examined the role of endothelins in the development and maintenance of primary and secondary hypertension. Evidence indicates that neither plasma ET-1 levels nor vascular responsiveness to ET-1 correlate with blood pressure in most experimental models of hypertension and in patients with primary or secondary hypertension. 1 Pinto-Sietsma S-J Paul M A role for endothelin in the pathogenesis of hypertension: Fact or fiction. Kidney Int. 1998; 54: S115-S121 Crossref Scopus (20) Google Scholar In fact, plasma ET-1 levels may best reflect the degree of atherosclerosis and vascular damage. 1 Pinto-Sietsma S-J Paul M A role for endothelin in the pathogenesis of hypertension: Fact or fiction. Kidney Int. 1998; 54: S115-S121 Crossref Scopus (20) Google Scholar ET-1 mainly should be viewed as an autocrine or paracrine factor; the peptide is secreted by and binds to multiple cell types that exhibit its biologic effects. In this respect, scant evidence exists that local vascular ET-1 is fundamentally important in primary or secondary hypertension 2 Markewitz BA Kohan DE Role of intrarenal endothelin in the generation and maintenance of hypertension. Miner Electr Metab. 1995; 21: 342-352 PubMed Google Scholar ; however, ET-1 may modulate blood pressure through mechanisms independent of direct vascular effects, such as regulation of renal sodium and water excretion, an area that also presents the greatest likelihood for uncovering a causal role for ET-1 in elevating blood pressure, and in clarifying the physiologic and pathophysiologic effects of ET-1.