title: Altered AT1 receptor regulation of ETB receptors in renal proximal tubule cells of spontaneously hypertensive rats.
abstract: The renin-angiotensin and endothelin systems regulate blood pressure, in part, by affecting renal tubular sodium transport. In rodents, ETB receptors decrease proximal tubular reabsorption, whereas AT1 receptors produce the opposite effect. We hypothesize that ETB and AT1 receptors interact at the receptor level, and that the interaction is altered in spontaneously hypertensive rats (SHRs). In immortalized renal proximal tubule (RPT) cells from Wistar-Kyoto (WKY) rats, angiotensin II, via AT1 receptors, increased ETB receptor protein in a time- and concentration-dependent manner. In contrast, in SHR RPT cells, angiotensin II (10(-8) M/24 hours) had no effect on ETB receptor protein. AT1/ETB receptors colocalized and co-immunoprecipitated in both rat strains but long-term angiotensin II (10(-8) M/24 hours) treatment increased AT1/ETB co-immunoprecipitation in WKY but not in SHR cells. Short-term angiotensin II (10(-8) M/15 minutes) treatment decreased ETB receptor phosphorylation in both WKY and SHR cells, and increased ETB receptors in RPT cell surface membranes of RPT cells in WKY but not SHRs. Basal cell surface membrane ETB receptor expression was also higher in WKY than in SHRs. We conclude that AT1 receptors regulate ETB receptors by receptor interaction and modulation of receptor expression. The altered AT1 receptor regulation of ETB receptors in SHRs may play a role in the pathogenesis of hypertension.
authors.affiliation: Department of Cardiology, Daping Hospital, Third Military Medical University, Chongqing, PR China. cyzeng1@hotmail.com
authors.forename: Chunyu
authors.initials: C
authors.lastname: Zeng
authors.forename: Ulrich
authors.initials: U
authors.lastname: Hopfer
authors.forename: Laureano D
authors.initials: LD
authors.lastname: Asico
authors.forename: Gilbert M
authors.initials: GM
authors.lastname: Eisner
authors.forename: Robin A
authors.initials: RA
authors.lastname: Felder
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Jose
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D015151:Immunoblotting; D047468:Immunoprecipitation; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology*; D011921:Rats, Inbred WKY; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology*; D044023:Receptor, Endothelin B / Q000378:metabolism*; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D044140:Receptor, Angiotensin, Type 1; D044023:Receptor, Endothelin B; D000804:Angiotensin II