Chronic blockade of endothelin A and B receptors using macitentan in experimental renovascular disease.

Background: Emerging research has identified the endothelin (ET)-1 pathway as a potential target for novel renoprotective therapies. We recently showed that selective ET-A receptor antagonism in chronic renovascular disease (RVD) improves renal function and reduces renal injury. Although ET-A and -B have opposing roles, in some clinical situations they may induce similar effects.

Endothelin-a receptor antagonism after renal angioplasty enhances renal recovery in renovascular disease.

Percutaneous transluminal renal angioplasty/stenting (PTRAS) is frequently used to treat renal artery stenosis and renovascular disease (RVD); however, renal function is restored in less than one half of the cases. This study was designed to test a novel intervention that could refine PTRAS and enhance renal recovery in RVD. Renal function was quantified in pigs after 6 weeks of chronic RVD (induced by unilateral renal artery stenosis), established renal damage, and hypertension.

Disparate effects of single endothelin-A and -B receptor blocker therapy on the progression of renal injury in advanced renovascular disease.

We hypothesized that chronic specific endothelin-A (ET-A) receptor blockade therapy would reverse renal dysfunction and injury in advanced experimental renovascular disease. To test this, unilateral renovascular disease was induced in 19 pigs, and after 6 weeks, single-kidney hemodynamics and function was quantified in vivo using computed tomography. All pigs with renovascular disease were divided such that seven were untreated, seven were treated with ET-A blockers, and five were treated with ET-B blockers.

Oxidative stress promotes hypertension and albuminuria during the autoimmune disease systemic lupus erythematosus.

Several lines of evidence suggest that essential hypertension originates from an autoimmune-mediated mechanism. One consequence of chronic immune activation is the generation of oxygen-derived free radicals, resulting in oxidative stress. Renal oxidative stress has direct prohypertensive actions on renal microvascular and tubular function.