Changes in angiotensin type 1 receptor binding and angiotensin-induced pressor responses in the rostral ventrolateral medulla of angiotensinogen knockout mice

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Publisher: American Physiological Society
Document Type: Author abstract; Report
Length: 301 words

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Abstract :

ANG II, the main circulating effector hormone of the renin-angiotensin system, is produced by enzymatic cleavage of angiotensinogen. The present study aimed to examine whether targeted deletion of the angiotensinogen gene (Agt) altered brain ANG II receptor density or responsiveness to ANG II. In vitro autoradiography was used to examine the distribution and density of angiotensin type 1 (ATe) and type 2 receptors. In most brain regions, the distribution and density of angiotensin receptors were similar in brains of Agt knockout mice ([Agt.sup.-/-]) and wild-type mice. In [Agt.sup.-/-] mice, a small increase in A[T.sub.1] receptor binding was observed in the rostral ventrolateral medulla (RVLM), a region that plays a critical role in blood pressure regulation. To examine whether [Agt.sup.-/-] mice showed altered responses to ANG II, blood pressure responses to intravenous injection (0.01-0.1 [micro]g/kg) or RVLM microinjection (50 pmol in 50 nl) of ANG II were recorded in anesthetized [Agt.sup.-/-] and wild-type mice. Intravenous injections of phenylephrine (4 [micro]g/kg and 2 [micro]g/kg) were also made in both groups. The magnitude of the pressor response to intravenous injections of ANG II or phenylephrine was not different between [Agt.sup.-/-] and wild-type mice. Microinjection of ANG II into the RVLM induced a pressor response, which was significantly smaller in [Agt.sup.-/-] compared with wild-type mice (+10 [+ or -] 1 vs. +23 [+ or -] 4 mmHg, respectively, P = 0.004). Microinjection of glutamate into the RVLM (100 pmol in 10 nl) produced a robust pressor response, which was not different between [Agt.sup.-/-]and wild-type mice. A diminished response to ANG II microinjection in the RVLM of [Agt.sup.-/-] mice, despite an increased density of A[T.sub.1] receptors suggests that signal transduction pathways may be altered in RVLM neurons of [Agt.sup.-/-] mice, resulting in attenuated cellular excitation. blood pressure; brain microinjection; angiotensin II; brain renin-angiotensin system doi: 10.1152/ajpregu.00462.2009

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Gale Document Number: GALE|A219141312