Increased expression of angiotensin peptides in the brain of transgenic hypertensive rats

Senanayake, P.; Moriguchi, Atsushi; Kumagai, Hiroo; Ganten, Detlev; Ferrario, Carlos M.; Brosnihan, K. Bridget

doi:10.1016/0196-9781(94)90051-5

Cited by 144 publications

(92 citation statements)

References 30 publications

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“…Similarly, microinjection of various specific AT 1 receptor antagonists (losartan, L-158,809, or CV-11974) in the RVLM of conscious rats produces a significant increase in MAP (12,13), suggesting that in the conscious state also the inhibitory effect of endogenous ANG II may predominate. On the other hand, in awake transgenic rats [TGR(mREN2)27] that overexpress the renin gene in the brain and that have increased levels of ANG II in the medulla (38), microinjection of CV-11974 in the RVLM produced a fall in MAP (12).…”

Section: Discussionmentioning

confidence: 99%

Blockade of AT₁ receptors in the rostral ventrolateral medulla increases sympathetic activity under hypoxic conditions

Sheriff¹,

Fontes²,

Killinger³

et al. 2006

American Journal of Physiology-Regulatory, Integrative and Comp

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The role of ANG type 1 (AT1) receptors in the rostral ventrolateral medulla (RVLM) in the maintenance of sympathetic vasomotor tone in normotensive animals is unclear. In this study, we tested the hypothesis that AT 1 receptors make a significant contribution to the tonic activity of presympathetic neurons in the RVLM of normotensive rats under conditions where the excitatory input to these neurons is enhanced, such as during systemic hypoxia. In urethane-anesthetized rats, microinjections of the AT1 receptor antagonist candesartan in the RVLM during moderate hypoxia unexpectedly resulted in substantial increases in arterial pressure and renal sympathetic nerve activity (RSNA), whereas under normoxic conditions the same dose resulted in no significant change in arterial pressure and RSNA. Under hypoxic conditions, and after microinjection of the GABA A receptor antagonist bicuculline in the RVLM, subsequent microinjection of candesartan in the RVLM resulted in a significant decrease in RSNA. In control experiments, bilateral microinjections in the RVLM of the compound [Sar 1 ,Thr 8 ]ANG II (sarthran), which decreases sympathetic vasomotor activity via a mechanism that is independent of AT 1 receptors, significantly reduced arterial pressure and RSNA under both normoxic and hypoxic conditions. The results indicate that, at least under some conditions, endogenous ANG II has a tonic sympathoinhibitory effect in the RVLM, which is dependent on GABA receptors. We suggest that the net effect of endogenous ANG II in this region depends on the balance of both tonic excitatory and inhibitory actions on presympathetic neurons and that this balance is altered in different physiological or pathophysiological conditions. brain stem; angiotensin receptors; arterial pressure; chemoreceptor reflex; sympathetic vasomotor tone; angiotensin type 1 receptor THE ROSTRAL PART OF THE ventrolateral medulla (RVLM) contains a group of sympathoexcitatory neurons that play a major role in the tonic and phasic regulation of sympathetic activity and arterial blood pressure (8, 16). These neurons project directly to sympathetic preganglionic neurons in the spinal cord and are an essential component of the central pathways mediating cardiovascular reflex responses to stimulation of baroreceptors, chemoreceptors, and many other peripheral receptors (8, 16).There is considerable evidence suggesting a role for endogenous ANG peptides in the regulation of RVLM neurons. Studies using in vitro autoradiography have demonstrated a high density of ANG II receptor binding sites in the RVLM of most species studied, including humans (2). These receptors are primarily of the ANG type 1 (AT 1 ) subtype (2), and recent studies using an antibody against the AT 1 receptor has confirmed the existence of these receptors on neurons in the RVLM of the rat, including catecholamine neurons of the C1 group (19). Microinjection of ANG II in the RVLM results in an increase in arterial pressure and sympathetic activity, an effect that is mediated by AT 1 receptors (3,14...

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Section: Discussionmentioning

confidence: 99%

Blockade of AT₁ receptors in the rostral ventrolateral medulla increases sympathetic activity under hypoxic conditions

Sheriff¹,

Fontes²,

Killinger³

et al. 2006

American Journal of Physiology-Regulatory, Integrative and Comp

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“…A number of studies have related the development of genetically pre-programmed hypertension in animal models to an increase in brain ANGII concentration (Phillips et al 1977;Des Senanayake et al 1994;Campbell et al 1995;Morishita et al 1995;Teruya et al 1995). NTS levels of AT1 receptors are elevated in spontaneously hypertensive rats (Gutkind et al 1988).…”

Section: Discussionmentioning

confidence: 99%

Differential effects of angiotensin II on cardiorespiratory reflexes mediated by nucleus tractus solitarii – a microinjection study in the rat

Paton

Kasparov

1999

The Journal of Physiology

101

120

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The nucleus tractus solitarii (NTS), the central site of termination of baroreceptive afferents, is intimately involved in arterial pressure control. This nucleus contains a high density of angiotensin II (ANGII) AT1 receptors located both presynaptically, on vagal and carotid sinus afferents, and on interneurones (Healy et al. 1989). It is well known that systemically injected ANGII has the unique ability to induce a pressor response with little or no reflex bradycardia. This is in striking contrast to virtually all other known pressor substances (reviewed in Reid, 1992;Bishop et al. 1995). One explanation of this phenomenon is that ANGII may attenuate the baroreceptor reflex by acting at the level of the NTS. In this regard, microinjection of ANGII into the NTS attenuated the baroreceptor reflex in both the anaesthetised normotensive adult rat (Casto & Phillips, 1986;Luoh & Chan, 1998) and the unanaesthetised rat (Michelini & Bonagamba, 1990). These data are consistent with results obtained following intracerebroventricular administration of ANGII (Hayashi et al. 1988). In our recent experiments, losartan blockade of AT1 receptors in the NTS increased baroreceptor reflex efficacy in the 10-20 day old rat (Kasparov et al. 1998) -an age when the baroreceptor reflex is depressed (Kasparov & Paton, 1997). In addition, AT1 receptor blockade in the NTS of mature

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“…23 Ang II measurements were made by radioimmunoassay, as previously described. 24,25 Aldosterone and estradiol concentrations were measured with the use of a commercially available radioimmunoassay (Diagnostic Product Corp). Serum triglycerides were determined by means of standard enzymatic methods on an automated system (ACE, Schiapparelli Bio Systems).…”

Section: Laboratory Analysesmentioning

confidence: 99%

Comparative Effects of Estrogen and Angiotensin-Converting Enzyme Inhibition on Plasminogen Activator Inhibitor-1 in Healthy Postmenopausal Women

et al. 2002

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Increased expression of angiotensin peptides in the brain of transgenic hypertensive rats

Cited by 144 publications

References 30 publications

Blockade of AT₁ receptors in the rostral ventrolateral medulla increases sympathetic activity under hypoxic conditions

Blockade of AT₁ receptors in the rostral ventrolateral medulla increases sympathetic activity under hypoxic conditions

Differential effects of angiotensin II on cardiorespiratory reflexes mediated by nucleus tractus solitarii – a microinjection study in the rat

Comparative Effects of Estrogen and Angiotensin-Converting Enzyme Inhibition on Plasminogen Activator Inhibitor-1 in Healthy Postmenopausal Women

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Increased expression of angiotensin peptides in the brain of transgenic hypertensive rats

Cited by 144 publications

References 30 publications

Blockade of AT1 receptors in the rostral ventrolateral medulla increases sympathetic activity under hypoxic conditions

Blockade of AT1 receptors in the rostral ventrolateral medulla increases sympathetic activity under hypoxic conditions

Differential effects of angiotensin II on cardiorespiratory reflexes mediated by nucleus tractus solitarii – a microinjection study in the rat

Comparative Effects of Estrogen and Angiotensin-Converting Enzyme Inhibition on Plasminogen Activator Inhibitor-1 in Healthy Postmenopausal Women

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Blockade of AT₁ receptors in the rostral ventrolateral medulla increases sympathetic activity under hypoxic conditions

Blockade of AT₁ receptors in the rostral ventrolateral medulla increases sympathetic activity under hypoxic conditions