Endothelin in hypertension: an update

Y Rautureau, EL Schiffrin - Current opinion in nephrology and …, 2012 - journals.lww.com
Y Rautureau, EL Schiffrin
Current opinion in nephrology and hypertension, 2012journals.lww.com
Pharmacological studies demonstrate that calcitonin gene-related peptide is a physiological
antagonist of ET-1 that terminates the long-lasting contraction induced by ET-1. ET-1-
induced rise in [Ca 2+] i involves the newly described stromal-interaction molecule-1/orai1
pathway to increase store-operated calcium entry. Sensitization of contractile proteins to
calcium during ET-1-induced contraction of vascular smooth muscle cells includes activation
of p63Rho guanine nucleotide exchange factor and increase in O-GlcNAcylation, a form of …
Summary
Pharmacological studies demonstrate that calcitonin gene-related peptide is a physiological antagonist of ET-1 that terminates the long-lasting contraction induced by ET-1. ET-1-induced rise in [Ca 2+] i involves the newly described stromal-interaction molecule-1/orai1 pathway to increase store-operated calcium entry. Sensitization of contractile proteins to calcium during ET-1-induced contraction of vascular smooth muscle cells includes activation of p63Rho guanine nucleotide exchange factor and increase in O-GlcNAcylation, a form of posttranslational modification. Genetically modified mice have demonstrated that endothelial ET-1 is involved in the regulation of normal blood pressure and development of vascular disease. Gene expression induced by endothelial overexpression of ET-1 in mice demonstrated upregulation of lipid metabolism, inflammatory and signal transduction genes. Crossing these mice with apoE−/− mice was associated with acceleration of atherosclerosis on a high-fat diet and blood pressure elevation. Finally, the DORADO clinical trial has demonstrated that the ET A-receptor antagonist darusentan is able to decrease the blood pressure of patients with refractory hypertension.
Lippincott Williams & Wilkins