Subpressor dose of angiotensin II increases susceptibility to the haemodynamic injury of blood pressure in Dahl salt-sensitive rats.
OBJECTIVE
To investigate the effects of subpressor doses of angiotensin II (Ang II) on the progression of renal injuries in Dahl salt-sensitive (Dahl-S) rats with hypertension.


METHODS
Rats were fed a high-salt (4% NaCl) diet and given an Ang II infusion (10 or 50 ng/kg per min, subcutaneously) for 4 weeks.


RESULTS
The plasma Ang II concentration achieved in the high-dose Ang II infusion was lower than that in low-salt (0.3% NaCl) normotensive rats. The Ang II infusion did not affect systolic blood pressure, cardiac hypertrophy or weight of thoracic aorta. However, the high-dose Ang II infusion increased proteinuria by 58%, enhanced the urinary N-acetyl-beta-D-glucosaminase index by 77% and reduced the glomerular filtration rate by 37%. The impaired renal function was associated with a progression of glomerulosclerotic lesions. Neither tubular nor arterial lesions were exacerbated. The infusion did not influence prostacyclin production or urinary cyclic GMP excretion.


CONCLUSIONS
A subpressor dose of Ang II infusion impairs renal function with progression of glomerulosclerosis, and these alterations may be due to increased susceptibility of the glomerulus in Dahl-S rats to Ang II-induced injuries. Such a mechanism might underlie a predisposition to hypertension-induced organ damage seen in Dahl-S rats with salt-induced hypertension.
Hirawa
N
N
Department of Nephrology, Kantoh-Teishin Hospital, Tokyo, Japan.
Uehara
Y
Y
Kawabata
Y
Y
Numabe
A
A
Ohshima
N
N
Ono
H
H
Gomi
T
T
Ikeda
T
T
Yagi
S
S
Toyo-oka
T
T
D000804:Angiotensin II / Q000097:blood / Q000633:toxicity*; D000818:Animals; D000242:Cyclic AMP / Q000652:urine; D006152:Cyclic GMP / Q000652:urine; D015777:Eicosanoids / Q000652:urine; D005919:Glomerular Filtration Rate / Q000187:drug effects; D005923:Glomerulosclerosis, Focal Segmental / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects*; D006973:Hypertension / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D007279:Injections, Subcutaneous; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008054:Lipid Peroxides / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats
D015777:Eicosanoids; D008054:Lipid Peroxides; D000804:Angiotensin II; D000242:Cyclic AMP; D006152:Cyclic GMP