Renal function in transgenic rats expressing an angiotensin-(1-7)-producing fusion protein.
Transgenic rats [TGR(A1-7)3292] present a chronic 2.5-fold increase in plasma Angiotensin-(1-7) [Ang-(1-7)] concentration. In the present study, we investigated the effects of this chronic elevation on renal function, vasopressin levels, kidney morphology, expression of Ang-(1-7) and vasopressin receptors in TGR(A1-7)3292. Urine volume and water intake were measured for 24 h. At the end of this period, plasma and urine samples were collected to evaluate renal function parameters and circulating vasopressin levels. Expression of renal V2 receptors and Mas was assessed by ribonuclease protection assay. Renal slices were processed for histological analysis. The urine flow of TGR(A1-7)3292 was significantly lower in comparison with Sprague-Dawley rats. The reduced urine volume of TGR(A1-7)3292 was accompanied by a significant increase in urinary osmolality and decrease free water clearance. Glomerular filtration rate, urinary sodium and potassium excretion were similar in both strains. No significant changes were observed in vasopressin levels as well as in V2 receptor and Mas mRNA expression in renal tissue. No changes in kidney structure of TGR(A1-7)3292 were detected. These data suggest that changes in circulating renin-angiotensin system produced by chronic increase of Ang-(1-7) levels can lead to adjustments in the water balance that are independent of vasopressin release and V2 receptor expression.
Ferreira
Anderson J
AJ
Department of Morphology, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
Pinheiro
Sérgio V B
SV
Castro
Carlos H
CH
Silva
Gerluza A B
GA
Silva
Ana Cristina Simões E
AC
Almeida
Alvair P
AP
Bader
Michael
M
Rentzsch
Brit
B
Reudelhuber
Timothy L
TL
Santos
Robson A S
RA
D000803:Angiotensin I / Q000097:blood / Q000235:genetics / Q000502:physiology*; D000818:Animals; D030801:Animals, Genetically Modified; D004231:Diuresis / Q000502:physiology; D006706:Homeostasis; D007668:Kidney / Q000502:physiology*; D008297:Male; D010446:Peptide Fragments / Q000097:blood / Q000235:genetics / Q000502:physiology*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D017483:Receptors, Vasopressin / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014667:Vasopressins / Q000097:blood
D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D017483:Receptors, Vasopressin; D011993:Recombinant Fusion Proteins; D014667:Vasopressins; D000803:Angiotensin I; C118790:angiotensin I (1-7)