ArticleThe Journal of pharmacology and experimental therapeutics2011
Distinct actions of endothelin A-selective versus combined endothelin A/B receptor antagonists in early diabetic kidney disease.
Article in The Journal of pharmacology and experimental therapeutics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 82 citations in OpenAlex.
- Inflammation as a therapeutic target to improve kidney and cardiovascular outcomes.Nature reviews. Nephrology · 2026Review
- SGLT2i, anti-endothelin A and double endothelin and angiotensin inhibitors: a new future for chronic kidney disease in children.Pediatric nephrology (Berlin, Germany) · 2026Review
- Endothelin receptor antagonism in sickle cell disease: Is the time now?Canadian journal of physiology and pharmacology · 2026Review
- Endothelin receptor antagonists in chronic kidney disease.Nature reviews. Nephrology · 2025Review
- Selective endothelin A receptor antagonism in chronic kidney disease: improving clinical application.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025Review
- Podocyte-targeted therapies - progress and future directions.Nature reviews. Nephrology · 2024Review
- Mechanism of protective actions of sparsentan in the kidney: lessons from studies in models of chronic kidney disease.Clinical science (London, England : 1979) · 2024Review
- Endothelin System in Hypertension and Chronic Kidney Disease.Hypertension (Dallas, Tex. : 1979) · 2024Review
- Endothelin mediates sex-differences in acclimation to high salt diet in rats.Biology of sex differences · 2023Article
- Population pharmacokinetic analysis of sparsentan in healthy volunteers and patients with focal segmental glomerulosclerosis.CPT: pharmacometrics & systems pharmacology · 2023Article
- Enhanced Cardiorenal Protective Effects of Combining SGLT2 Inhibition, Endothelin Receptor Antagonism and RAS Blockade in Type 2 Diabetic Mice.International journal of molecular sciences · 2022Article
- Sickle cell nephropathy: A review of novel biomarkers and their potential roles in early detection of renal involvement.World journal of clinical pediatrics · 2022Review
- Should Renal Inflammation Be Targeted While Treating Hypertension?Frontiers in physiology · 2022Review
- The acute pressure natriuresis response is suppressed by selective ETA receptor blockade.Clinical science (London, England : 1979) · 2021Article
- Hydroxyurea improves nitric oxide bioavailability in humanized sickle cell mice.American journal of physiology. Regulatory, integrative and comparative physiology · 2021Article
- Early functional and metabolic disorders in children with type I diabetes mellitus and diabetic nephropathy.Pediatric endocrinology, diabetes, and metabolism · 2021Article
- Article
- Combined hydroxyurea and ETActa physiologica (Oxford, England) · 2019Article
- Prevention of the progression of renal injury in diabetic rodent models with preexisting renal disease with chronic endothelin A receptor blockade.American journal of physiology. Renal physiology · 2018Article
- Early life stress induces immune priming in kidneys of adult male rats.American journal of physiology. Renal physiology · 2018Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Selective endothelin A (ET(A)) and combined ET(A) and ET(B) receptor antagonists are being investigated for use in treating diabetic nephropathy. However, the receptor-specific mechanisms responsible for producing the potential benefits have not been discerned. Thus, we determined the actions of ET(A) and ET(B) receptors on measures of glomerular function and renal inflammation in the early stages of diabetic renal injury in rats through the use of selective and combined antagonists. Six weeks after streptozotocin (STZ)-induced hyperglycemia, rats were given 2R-(4-methoxyphenyl)-4S-(1,3-benzodioxol-5-yl)-1-(N,N-di(n-butyl)aminocarbonyl-methyl)-pyrrolidine-3R-carboxylic acid (ABT-627) (5 mg/kg/day), a selective ET(A) antagonist; (2R,3R,4S)-4-(benzo[d][1,3]dioxol-5-yl)-2-(3-fluoro-4-methoxyphenyl)-1-(2-(N-propylpentylsulfonamido)ethyl)pyrrolidine-3-carboxylic acid hydrochloride (A-182086) (10 mg/kg/day), a combined ET(A/B) antagonist; or vehicle for 1 week. Sham controls received STZ vehicle (saline). Hyperglycemia led to significant proteinuria, increased glomerular permeability to albumin (P(alb)), nephrinuria, and an increase in total matrix metalloprotease (MMP) and transforming growth factor-β1 (TGF-β1) activities in glomeruli. Plasma and glomerular soluble intercellular adhesion molecule-1 (sICAM-1) and monocyte chemoattractant protein-1 (MCP-1) were elevated after 7 weeks of hyperglycemia. Daily administration of both ABT-627 and A-182086 for 1 week significantly attenuated proteinuria, the increase in P(alb), nephrinuria, and total MMP and TGF-β1 activity. However, glomerular sICAM-1 and MCP-1 expression was attenuated with ABT-627, but not A-182086, treatment. In summary, both selective ET(A) and combined ET(A/B) antagonists reduced proteinuria and glomerular permeability and restored glomerular filtration barrier component integrity, but only ET(A)-selective blockade had anti-inflammatory and antifibrotic effects. We conclude that selective ET(A) antagonists are more likely to be preferred for the treatment of diabetic kidney disease.
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