1. Attenuation of renal vasopressin V 2 receptor upregulation by bosentan, an ETA/ETB receptor antagonist
- Author
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Joseph K.C. Tsui, Marc Sonntag, and Norman L.M. Wong
- Subjects
Endothelin Receptor Antagonists ,Male ,Receptors, Vasopressin ,Vasopressin ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Hamster ,In situ hybridization ,Aquaporins ,Endocrinology ,Downregulation and upregulation ,Cricetinae ,Internal medicine ,Arginine vasopressin receptor 2 ,Animals ,Medicine ,RNA, Messenger ,Kidney Tubules, Collecting ,In Situ Hybridization ,Kidney Medulla ,Sulfonamides ,Aquaporin 2 ,Endothelin-1 ,Reverse Transcriptase Polymerase Chain Reaction ,urogenital system ,business.industry ,Bosentan ,Receptor, Endothelin A ,Receptor, Endothelin B ,Aquaporin 6 ,Gene Expression Regulation ,business ,Endothelin receptor ,hormones, hormone substitutes, and hormone antagonists ,medicine.drug - Abstract
Circulating endothlein (ET) levels are elevated in heart failure and positively correlated with severity of heart failure. Recent studies demonstrated arginine vasopressin (AVP) V 2 mRNA expression was upregulated in the inner medullary collecting duct (IMCD) of cardiomyopathic hamsters (CM). The goal of the present studies was to determine if ET-1 is involved in upregulating the expression of AVP V 2 mRNA in the IMCD of CM by using a mixed ETA/ETB receptor antagonist bosentan. Our results showed plasma ET-1 levels increased in CM hamsters and related with the severity of heart failure. The competitive reverse-transcriptase polymerase chain reaction (RT-PCR) method was used to quantify the expression of AVP V 2 and aquaporin 2 (AQP2) mRNA in the IMCD. AVP V 2 mRNA expression was elevated in placebo-treated CM hamsters and decreased significantly with 14 days of bosentan treatment. Similar results were seen with AQP2 mRNA. The effect of bosentan in normalizing the expression of AVP V 2 and AQP2 mRNA in the IMCD of CM was confirmed by in situ hybridization studies. Bosentan treatments reduced the intensitites of the signals in the IMCD of CM hamsters to that seen in normal hamsters. This study demonstrated that AVP V 2 and AQP2 mRNA are upregulated in CM hamsters and these upregulations are attenuated by bosentan treatment, suggesting that ET-1 plays a role in upregulating the expression of AVP V 2 mRNA in CM hamsters.
- Published
- 2003