title: The effects of angiotensin II and angiotensin-(1-7) in the rostral ventrolateral medulla of rats on stress-induced hypertension.
abstract: We have shown that angiotensin II (Ang II) and angiotensin-(1-7) [Ang-(1-7)] increased arterial blood pressure (BP) via glutamate release when microinjected into the rostral ventrolateral medulla (RVLM) in normotensive rats (control). In the present study, we tested the hypothesis that Ang II and Ang-(1-7) in the RVLM are differentially activated in stress-induced hypertension (SIH) by comparing the effects of microinjection of Ang II, Ang-(1-7), and their receptor antagonists on BP and amino acid release in SIH and control rats. We found that Ang II had greater pressor effect, and more excitatory (glutamate) and less inhibitory (taurine and γ-aminobutyric acid) amino acid release in SIH than in control animals. Losartan, a selective AT₁ receptor (AT₁R) antagonist, decreased mean BP in SIH but not in control rats. PD123319, a selective AT₂ receptor (AT₂R) antagonist, increased mean BP in control but not in SIH rats. However, Ang-(1-7) and its selective Mas receptor antagonist Ang779 evoked similar effects on BP and amino acid release in both SIH and control rats. Furthermore, we found that in the RVLM, AT₁R, ACE protein expression (western blot) and ACE mRNA (real-time PCR) were significantly higher, whereas AT₂R protein, ACE2 mRNA and protein expression were significantly lower in SIH than in control rats. Mas receptor expression was similar in the two groups. The results support our hypothesis and demonstrate that upregulation of Ang II by AT₁R, not Ang-(1-7), system in the RVLM causes hypertension in SIH rats by increasing excitatory and suppressing inhibitory amino acid release.
authors: Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai, China.
authors: Dongshu
authors: D
authors: Du
authors: Jun
authors: J
authors: Chen
authors: Min
authors: M
authors: Liu
authors: Minxia
authors: M
authors: Zhu
authors: Haojia
authors: H
authors: Jing
authors: Jie
authors: J
authors: Fang
authors: Linlin
authors: L
authors: Shen
authors: Danian
authors: D
authors: Zhu
authors: Jerry
authors: J
authors: Yu
authors: Jin
authors: J
authors: Wang
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000803:Angiotensin I / Q000494:pharmacology* / Q000627:therapeutic use; D000804:Angiotensin II / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D010446:Peptide Fragments / Q000494:pharmacology* / Q000627:therapeutic use; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects; D013315:Stress, Psychological / Q000150:complications*
chemical_list: D000596:Amino Acids; D000959:Antihypertensive Agents; D010446:Peptide Fragments; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; C118790:angiotensin I (1-7)
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