Regulation of Blood Pressure and Salt Homeostasis by Endothelin

Abstract

Endothelin (ET) peptides and their receptors are intimately involved in the physiological control of systemic blood pressure and body Na homeostasis, exerting these effects through alterations in a host of circulating and local factors. Hormonal systems affected by ET include natriuretic peptides, aldosterone, catecholamines, and angiotensin. ET also directly regulates cardiac output, central and peripheral nervous system activity, renal Na and water excretion, systemic vascular resistance, and venous capacitance. ET regulation of these systems is often complex, sometimes involving opposing actions depending on which receptor isoform is activated, which cells are affected, and what other prevailing factors exist. A detailed understanding of this system is important; disordered regulation of the ET system is strongly associated with hypertension and dysregulated extracellular fluid volume homeostasis. In addition, ET receptor antagonists are being increasingly used for the treatment of a variety of diseases; while demonstrating benefit, these agents also have adverse effects on fluid retention that may substantially limit their clinical utility. This review provides a detailed analysis of how the ET system is involved in the control of blood pressure and Na homeostasis, focusing primarily on physiological regulation with some discussion of the role of the ET system in hypertension.

Plasma Renin Activity and Aldosterone Concentrations in Hypertensive Cats with and without Azotemia and in Response to Treatment with Amlodipine Besylate

“…A recent study suggests that bilateral adrenocortical hyperplasia is an almost ubiquitous finding in cats >9 years (97%), but there was no significant difference in histopathologic grading between hypertensive (n = 37) and normotensive cats (n = 30), supporting that adrenocortical hyperplasia is unlikely to be a primary factor in feline hypertension 13. A number of other factors have been demonstrated to modulate aldosterone production apart from angiotensin II including extracellular potassium concentration, adrenocorticotropic hormone, adrenomedullin, atrial natriuretic peptide, dopamine, endogenous digitalis‐like factors (eg, ouabain) and endothelin‐1, but the effect these play in regulating aldosterone production in the cat has not been investigated 24, 25, 26, 27, 28, 29…”

oxLDL induces injury and defenestration of human liver sinusoidal endothelial cells via LOX1

“…ET1 is a potent vasoconstrictor peptide, and both ET1 and NO play pivotal roles in vascular homoeostasis (Kauser et al 2000). ET1 and NO work as negative feedback signals for each other (Li et al 2003, Oishi et al 2006, Kohan et al 2011. The reduced activation of eNOS is a characteristic of vascular endothelial dysfunction (Wohlfart et al 2008), and ET1 could promote early events leading to endothelial dysfunction and AS (Rautureau & Schiffrin 2012).…”

Acute Pressor Response to Psychosocial Stress Is Dependent on Endothelium‐Derived Endothelin‐1

“…ET‐1 is a nanomolar potent peptide produced by diverse cell types throughout the body that functions in autocrine and paracrine signaling 9, 10. Multiple studies have demonstrated an increase in plasma ET‐1 levels in response to laboratory‐induced acute psychosocial stress in healthy, at risk, and diseased human subjects 2, 11, 12, 13, 14, 15, 16.…”