Prevention of salt-induced hypertension and fibrosis by AT1-receptor blockers in Dahl S rats

Abstract

In Dahl S rats, high salt intake causes hypertension and cardiovascular hypertrophy and fibrosis, associated with an apparent increase in activity of tissue RAAS. In the current study, we assessed the effects of two AT1-receptor blockers (ARB) on AT1- and AT2-receptors and ACE densities and salt-induced cardiovascular changes. The hydrophilic ARB losartan (30 or 100 mg.kg.d) and the lipophilic ARB telmisartan (10 or 30 mg.kg.d) were administered once daily, and a high-salt diet was provided from 5 to 9 weeks. In Dahl S but not R rats, the high-salt diet caused marked hypertension, cardiac and kidney hypertrophy, and fibrosis. Both ARBs dose-dependently inhibited binding of Ang II to AT1-receptors and reversed the salt-induced increases in AT2-receptor densities in the CNS. Both ARBs at regular doses attenuated the salt-induced hypertension and, at high doses, prevented the increase in BP during the day but not during the night. Both ARBs similarly prevented high-salt-induced interstitial and perivascular fibrosis in the LV and RV as well as fibrosis in the aorta and renal tubules. RV hypertrophy was also prevented, but LV hypertrophy only partially, and kidney hypertrophy not at all. In Dahl S rats, AT1-receptor stimulation seems to play a critical role in salt-induced hypertension and fibrosis, but a lesser role in tissue hypertrophy.