SUBPRESSOR DOSE OF ANGIOTENSIN-II INCREASES SUSCEPTIBILITY TO THE HEMODYNAMIC 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, card iac 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. Conclusion: 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.