Role of endothelin in preeclampsia and hypertension following antiangiogenesis treatment

Abstract

Activation of the endothelin axis has now emerged as a crucial player in the manifestations of preeclampsia and following antiangiogenic treatment. As a consequence, blockade of the endothelin system may be considered as a treatment option both in preeclampsia and in antiangiogenesis-induced hypertension and renal toxicity in patients with cancer.

Hypertension: Current trends and future perspectives

“…Both situations are associated with activation of the endothelin system. 36 Antiangiogenic therapy is associated with the development of hypertension and proteinuria, 37 with a thrombotic microangiopathy commonly identified on the renal biopsy of those affected. 38 These adverse effects, seen in 30% of those on treatment, can be treatment-limiting, but simultaneously can be predictive of an antitumour response.…”

Angiogenic Factors in Preeclampsia

“…The cause of hypertension by sFlt1 has been described to be because of decreased endothelial nitric oxide production and increased endothelin secretion. 34,35 However, other factors such as prostacyclins and hydrogen sulfide that are downstream of the VEGF receptor may also be involved. 36,37 The microvasculature of organs affected in preeclampsia such as the glomeruli and hepatic sinusoidal vasculature are more permeable because of the presence of intracellular perforations referred to as fenestrations.…”

Sex-Specific Contributions of Endothelin to Hypertension

“…ET-1 also appears to induce oxidative stress in preeclampsia [39, 40]. Importantly, ET A receptor blockade provides protection against preeclampsia [36, 41–43]. ET A receptor antagonism prevents/reduces the hypertension in many experimental models of preeclampsia, highlighting that ET-1 signaling is a common contributor to elevated blood pressure in pregnancy [44].…”