Subfornical organ. Does it protect against angiotensin II-induced hypertension in the rat?

“…Although AngII-induced hypertension in the mouse is salt-dependent (Cholewa et al , 2005), the contribution of the SFO to AngII-salt hypertension has not been investigated in this species. In an earlier study we reported that lesion of the SFO exacerbated, rather than attenuated, AngII induced hypertension in rats on a high salt intake (Bruner et al , 1985). However, in that study daily sodium intake was increased by intravenous infusion of isotonic saline, and AngII was infused intravenously for only 5 days.…”

Section: Introductionmentioning

confidence: 99%

The role of the subfornical organ in angiotensin II–salt hypertension in the rat

Osborn

Hendel

Collister

et al. 2011

Experimental Physiology

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Hypertension caused by chronic infusion of angiotensin II (AngII) in experimental animals is dependent, in part, on increased activity of the sympathetic nervous system. This chronic sympathoexcitatory response is amplified by a high salt diet suggesting an interaction of circulating AngII and dietary salt on sympathetic regulatory pathways in the brain. The present study tested the hypothesis that the subfornical organ (SFO), a forebrain circumventricular organ known to be activated by circulating AngII, is crucial to the pathogenesis of hypertension induced by chronic AngII administration in rats on a high salt diet (AngII-salt model). Rats were randomly selected to undergo either subfornical organ lesion (SFOx) or sham surgery (SHAM) and then placed on a high salt (2% NaCl) diet. One week later rats were instrumented for radiotelemetric measurement of mean arterial pressure (MAP) and heart rate (HR) and placed in metabolic cages to measure sodium and water balance. Baseline MAP was slightly (but not statistically) lower in SFOx compared to SHAM rats during the 5 day control period. During the subsequent 10 days of AngII administration, MAPwas statistically lower in SFOx rats. However, when MAP responses to AngII were analyzed by comparing the change from the 5 day baseline period, only on the 5th day of AngII was MAP significantly different between groups. There were no differences between groups for water or sodium balance throughout the protocol. We conclude that, although the SFO is required for the complete expression of AngII-salt hypertension in the rat, other brains sites are also involved.

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“…19 Intravenous Ang II causes a pressor response that can be blocked by lesion of the SFO. 20,21 Interestingly though, chronic Ang II hypertension is exacerbated in rats with lesions of the SFO, 22 suggesting that the effects of Ang II at the SFO are quite different, depending on the chronicity. In 1970, the idea that the pressor response to Ang II at the SFO was sympathetically mediated was proposed.…”

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confidence: 99%

Role of the Subfornical Organ in the Chronic Hypotensive Response to Losartan in Normal Rats

Collister

Hendel

2003

Hypertension

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Abstract-Angiotensin II is known to act at a unique set of brain regions known as the circumventricular organs. These structures lack the normal blood-brain barrier and are therefore thought to participate in the central nervous system processing of neuroendocrine signals. We have reported that chronic treatment with the angiotensin type 1 (AT 1 ) receptor antagonist, losartan, decreases arterial pressure in normotensive rats. Furthermore, this hypotension is attenuated in area postrema-lesioned rats, suggesting a role of endogenous angiotensin II at this circumventricular organ. Another circumventricular organ, the subfornical organ (SFO), has also been shown to mediate actions of angiotensin II. The present study tested the hypothesis that the SFO is a central site of action of endogenous angiotensin II at AT 1 receptors. Adult male Sprague-Dawley rats were anesthetized and placed in a stereotaxic apparatus, and the SFO was sham or electrolytically lesioned. One week later, rats were instrumented with venous catheters and radiotelemetry pressure transducers for continuous infusion and monitoring of mean arterial pressure, respectively. After 3 days of control, losartan was administered intravenously (10 mg ⅐ kg Ϫ1 ⅐ d Ϫ1 ) for 10 days in both SFO-lesioned and sham rats. By day 4 of losartan administration, mean arterial pressure had decreased to 75Ϯ2 mm Hg in sham rats (nϭ9) but had only fallen to 83Ϯ2 mm Hg in lesioned rats (nϭ10). This attenuated hypotensive response in SFO-lesioned rats continued through day 10 of losartan treatment. These results support the hypothesis that the SFO mediates part of the hypotensive effects of chronic AT 1 receptor blockade in the normotensive rat. Key Words: antagonists, angiotensin Ⅲ autonomic nervous system Ⅲ blood pressure Ⅲ brain Ⅲ receptors, angiotensin II Ⅲ renin-angiotensin system Ⅲ circumventricular organ T he role of the renin-angiotensin system (RAS) in chronic blood pressure regulation is still not fully understood and continues to be studied. Much of our current understanding of this system is based on the response of arterial pressure to drugs that block the RAS, including ACE inhibitors and angiotensin type 1 (AT 1 ) receptor antagonists. We have demonstrated a profound chronic hypotensive response to the AT 1 receptor antagonist losartan in normotensive, salt-replete rats. 1 After 10 days of losartan treatment, rats consuming a normal-salt diet demonstrated a progressive hypotensive response of Ϸ35 mm Hg. This clearly shows an important role of this hormone in the maintenance of arterial pressure in normal animals, and yet, we do not fully understand the mechanism of this response.The mechanism by which blockade of the endogenous RAS lowers arterial pressure chronically is difficult to determine because of the numerous actions of angiotensin (Ang) II, which include vasoconstriction, 2 renal retention of sodium and water, 3-5 sympathoexcitation, 6 and vascular hypertrophy. 7 It has been reported that chronic low-dose Ang II hypertension is not solely caused by...

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Subfornical organ. Does it protect against angiotensin II-induced hypertension in the rat?

Cited by 22 publications

References 20 publications

Circulating angiotensin II and dietary salt: Converging signals for neurogenic hypertension

Circulating angiotensin II and dietary salt: Converging signals for neurogenic hypertension

The role of the subfornical organ in angiotensin II–salt hypertension in the rat

Role of the Subfornical Organ in the Chronic Hypotensive Response to Losartan in Normal Rats

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