Diuresis and natriuresis produced by long term administration of a selective Angiotensin-(1-7) antagonist in normotensive and hypertensive rats.
In this study we evaluated the renal effects of chronic administration of the selective Angiotensin-(1-7)[Ang-(1-7)] antagonist, A-779, in normotensive and spontaneously hypertensive rats (SHR). Male adult SHR and Wistar rats were housed in metabolic cages with tap water and standard chow, for three-five days before starting infusion (Alzet osmotic mini-pumps) of A-779 (Wistar: 1 microg/h, n = 9; 2.5 microg/h, n = 6; SHR:2.5 microg/h, n = 6) or vehicle (0.9% NaCl - 1 microl/h, n = 7 and n = 10 for SHR and Wistar rats, respectively). Urine volume, water and food intake and urinary Na+ were measured daily. On the last day of infusions mean arterial pressure (MAP) was recorded and urine and blood samples were collected to determine renal function parameters. Chronic infusion of A-779 produced a sustained increase in diuresis in normotensive rats [seventh day values: 0.75+/-0.08 ml/h (1 microg/h) and 0.94+/-0.13 ml/h (2.5 microg/h) vs. 0.42 + 0.03 ml/h for the control group, P<0.05] associated to a dose-dependent increase in the creatinine clearance. In SHR, diuresis increased significantly after chronic infusion of A-779 (fifth day values: 0.44 + 0.06 ml/h vs. 0.25+/-0.04 ml/h for the control group, P<0.05), without changes in creatinine clearance. Infusion of A-779 in normotensive rats produced a decrease in water reabsorption. A-779 infusion also produced a dose-dependent increase in urinary Na+ excretion (1.49 + 0.14 mEq, 1 microg/h vs. 2.37+/-0.22 mEq, 2.5 microg/h, P<0.05), in Wistar rats, without modifying the fractional excretion of Na+. In SHR, urinary Na+ excretion was also increased by A-779 (2.21+/-0.46 mEq vs. 0.94+/-0.22 mEq for the control group, P<0.05). No significant changes in blood pressure were observed. These findings suggest that endogenous Ang-(l-7) participates in the control of hydroelectrolyte balance by modulating water excretion, acting at tubular and glomerular sites.
Simões e Silva
A C
AC
Laboratório de Hipertensão, Departamento de Fisiologia e Biofísica, ICB-UFMG, Belo Horizonte, MG, Brazil.
Bello
A P
AP
Baracho
N C
NC
Khosla
M C
MC
Santos
R A
RA
D000803:Angiotensin I; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D004231:Diuresis / Q000187:drug effects*; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D013997:Time Factors
C092006:7-Ala-angiotensin (1-7); D010446:Peptide Fragments; D000804:Angiotensin II; D000803:Angiotensin I; C118790:angiotensin I (1-7)