AT1 receptor in rostral ventrolateral medulla mediating blunted baroreceptor reflex in spontaneously hypertensive rats.
OBJECTIVE
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 microg/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 AT1 receptor antisense oligodeoxynucleotides into the RVLM. AT1 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.


CONCLUSIONS
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.
Gao
Xin-ya
XY
Department of Physiology, Nanjing Medical University, China.
Zhang
Feng
F
Han
Ying
Y
Wang
Han-jun
HJ
Zhang
Ying
Y
Guo
Rui
R
Zhu
Guo-qing
GQ
D000804:Angiotensin II / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D017704:Baroreflex / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology*; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism
D047228:Angiotensin II Type 1 Receptor Blockers; D020319:Oligodeoxyribonucleotides, Antisense; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D010656:Phenylephrine; D019808:Losartan