Endothelin-1 has potent vasoconstrictor and vasopressor actions contributing to basal vascular tone and maintenance of blood pressure acting predominantly through endothelin-A receptors. Endothelin antagonists may be of value in the treatment of hypertension and heart failure. However, the role of endothelin-1 in the regulation of vascular tone and the potential benefits of endothelin antagonis...

Background & Objective: As the prostate adenocarcinoma is one of the most common malignant tumors in males, looking for a marker to effectively predict aggressiveness and metastatic potential in an apparently localized cancer in initial needle biopsy specimens can help the clinicians to make more appropriate decision for treatment, planning, and choosing appropriate ta...

Slow dissociation of endothelin 1 from its endothelin A receptors is responsible for the long-lasting vasoconstrictor effects of the peptide. We showed recently that calcitonin gene-related peptide selectively terminates long-lasting contractile responses to endothelin 1 in isolated rat mesenteric arteries. Here we assessed whether the antiendothelinergic effect of calcitonin gene-related pepti...

Endothelin is a potent vasoconstrictor peptide produced by endothelial cells, but its role in physiology and disease is uncertain. We investigated the influence of the endothelin-A-selective receptor antagonist PD 147953 and the nonselective endothelin receptor antagonist PD 145065 on the effects of endothelin-1 and endothelin-3 in the skin microcirculation of healthy volunteers, using laser Do...

The role of endothelin B (ET(B)) receptors in inflammation and nociception was examined using ET(B) receptor knockout mice. Genotyping studies were used with tissues from ET(B)((+/+)), ET(B)((+/-)), and ET(B)((-/-)) mice to confirm the loss of ET(B) receptors. Algesia induced by phenylbenzoquinone was evident in the (+/+) mice, reduced by approximately 80% in the (+/-) mice, and absent in the (...

When mutations in two different genes produce the same mutant phenotype, it suggests that the encoded proteins either interact with each other, or act in parallel to fulfill a similar purpose. Haploinsufficiency of Neurofibromin and over-expression of Endothelin 3 both cause increased numbers of melanocytes to populate the dermis during mouse development, and thus we are interested in how these...

BACKGROUND The relative efficacy of endothelin-A (ET(A)) receptor blockade versus combined ET(A)-ET(B) receptor blockade in chronic heart failure (CHF) is still largely unknown. METHODS AND RESULTS We compared, in a rat model of CHF (coronary ligation), the hemodynamic and structural effects of 1 month of treatment with the ET(A) antagonist ABT-627 (5 mg x kg(-1) x d(-1)), the ET(B) antagonis...

This study investigates gene therapy with human tissue kallikrein as a treatment for fructose-induced hypertension in rats. Hypertension was induced by addition of 10% fructose to drinking water. Fructose-fed rats also had increased serum insulin and triglycerides, decreased urine osmolarity, increased urine volume and endothelin-1, and increased aortic endothelin-1, endothelin-A receptor, and ...