AT₁ receptor in rostral ventrolateral medulla mediating blunted baroreceptor reflex in spontaneously hypertensive rats

AIM: To determine the role of AT₁ receptor in the rostral ventrolateral medulla (RVLM) in mediating the blunted baroreceptor reflex in spontaneously hypertensive rats (SHR). METHODS: Intravenous injections of graded doses of phenylephrine (1, 5, 10, 20, and 40 μg/kg) increased the blood pressure to elicit the baroreceptor reflex in both SHR and normotensive Wistar rats anesthetized with urethane. The baroreceptor reflex sensitivity (BRS) was determined before and after microinjection of Ang II, losartan, or AT ₁ receptor antisense oligodeoxynucleotides into the RVLM. AT ₁ receptor protein level in the RVLM was measured by Western blotting. RESULTS: The BRS was significantly decreased in SHR compared with normal rats. Bilateral microinjection of AT₁ receptor antagonist losartan (250 nmol/h) into the RVLM partly reversed the blunted BRS in SHR, but had no significant effect on the BRS in normal rats. Ang II (1.5 nmol/h) significantly inhibited the BRS in normal rats, which was completely abolished by pretreatment with losartan. However, no significant change in the BRS was observed after microinjection of Ang II into the RVLM in SHR. Bilateral microinjection of AT₁ receptor antisense oligodeoxynucleotides (ASODN) into the RVLM partially recovered the blunted BRS in SHR after 3 h, but no significant change in the BRS was observed in normal rats. The AT₁ receptor protein level significantly decreased after administration of ASODN. CONCLUSION: Blockage of AT₁ receptor or inhibition of AT₁ receptor protein synthesis in the RVLM enhanced the BRS in SHR, suggesting that the enhanced activities of AT₁ receptor in the RVLM contribute to the blunted BRS in SHR.