Autoradiographic localization of subtypes of angiotensin II antagonist binding in the rat brain

Gehlert, Donald R.; Gackenheimer, Susan L.; Schober, Douglas A.

doi:10.1016/0306-4522(91)90073-w

Cited by 160 publications

(59 citation statements)

References 35 publications

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“…Both types of A-II receptors have been described previously in a number of hypothalamic nuclei (Gehlert et al, 1991;Song et al, 1992;Phillips et al, 1993;Lenkei et al, 1995Lenkei et al, , 1996Lenkei et al, , 1998Oldfield et al, 2001;Thomas et al, 2003). Previous studies have demonstrated that radioligand binding of saralasin in the DMH and surrounding regions was blocked by previous incubation with a specific AT 1 R antagonist (i.e., losartan) but not with an A-II type 2 receptor antagonist (i.e., WL19), suggesting that saralasin injections in the DMH block panic-like responses by acting at AT 1 R (Gehlert et al, 1991;Song et al, 1992).…”

Section: Discussionmentioning

confidence: 81%

“…Previous studies have demonstrated that radioligand binding of saralasin in the DMH and surrounding regions was blocked by previous incubation with a specific AT 1 R antagonist (i.e., losartan) but not with an A-II type 2 receptor antagonist (i.e., WL19), suggesting that saralasin injections in the DMH block panic-like responses by acting at AT 1 R (Gehlert et al, 1991;Song et al, 1992). The presence of AT 1 R, but either low expression or no AT 2 Rs, in the DMH is also consistent with other radioligand binding (Israel et al, 1985;Obermuller et al, 1991;Hauser et al, 1998) (for review, see Allen et al, 1998) and mRNA expression (for review, see Lenkei et al, 1997) in the hypothalamus, including the DMH (Johren et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

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Angiotensin-II Is a Putative Neurotransmitter in Lactate-Induced Panic-Like Responses in Rats with Disruption of GABAergic Inhibition in the Dorsomedial Hypothalamus

Shekhar¹,

Johnson²,

Sajdyk³

et al. 2006

J. Neurosci.

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Intravenous sodium lactate infusions or the noradrenergic agent yohimbine reliably induce panic attacks in humans with panic disorder but not in healthy controls. However, the exact mechanism of lactate eliciting a panic attack is still unknown. In rats with chronic disruption of GABA-mediated inhibition in the dorsomedial hypothalamus (DMH), achieved by chronic microinfusion of the glutamic acid decarboxylase inhibitor L-allylglycine, sodium lactate infusions or yohimbine elicits panic-like responses (i.e., anxiety, tachycardia, hypertension, and tachypnea). In the present study, previous injections of the angiotensin-II (A-II) type 1 receptor antagonist losartan and the nonspecific A-II receptor antagonist saralasin into the DMH of "panic-prone" rats blocked the anxiety-like and physiological components of lactate-induced panic-like responses. In addition, direct injections of A-II into the DMH of these panic-prone rats also elicited panic-like responses that were blocked by pretreatment with saralasin. Microinjections of saralasin into the DMH did not block the panic-like responses elicited by intravenous infusions of the noradrenergic agent yohimbine or by direct injections of NMDA into the DMH. The presence of the A-II type 1 receptors in the region of the DMH was demonstrated using immunohistochemistry. Thus, these results implicate A-II pathways and the A-II receptors in the hypothalamus as putative substrates for sodium lactate-induced panic-like responses in vulnerable subjects.

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Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Angiotensin-II Is a Putative Neurotransmitter in Lactate-Induced Panic-Like Responses in Rats with Disruption of GABAergic Inhibition in the Dorsomedial Hypothalamus

Shekhar¹,

Johnson²,

Sajdyk³

et al. 2006

J. Neurosci.

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“…Extensive evidence supports the idea that Ang II signaling mediates ROS generation, 2,5,30 and the NTS contains a high density of Ang II subtype 1 receptors located on both vagal and carotid sinus afferent terminals presynaptically and on neurons postsynaptically. 13,31 The role of Ang II in the NTS, however, is complicated. Depending on the dose, microinjection of Ang II into the NTS elicits an increase or decrease in blood pressure.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Rac1-Derived Reactive Oxygen Species in Nucleus Tractus Solitarius Decreases Blood Pressure and Heart Rate in Stroke-Prone Spontaneously Hypertensive Rats

et al. 2007

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Abstract-Reactive oxygen species (ROS) in the brain are thought to contribute to the neuropathogenesis of hypertension by enhancing sympathetic nervous system activity. The nucleus tractus solitarius (NTS), which receives afferent input from baroreceptors, has an important role in cardiovascular regulation. reduced nicotinamide-adenine dinucleotide phosphate oxidase is thought to be a major source of ROS in the NTS. Rac1 is a small G protein and a key component of reduced nicotinamide-adenine dinucleotide phosphate oxidase. The role of Rac1-derived ROS in the NTS in cardiovascular regulation of hypertension is unknown. Therefore, we examined whether inhibition of Rac1 in the NTS decreases ROS generation, thereby reducing blood pressure in stroke-prone spontaneously hypertensive rats (SHRSPs).The basal Rac1 activity level in the NTS was greater in SHRSPs than in Wistar-Kyoto rats. Inhibition of Rac1, induced by transfecting adenovirus vectors encoding dominant-negative Rac1 into the NTS, decreased blood pressure, heart rate, and urinary norepinephrine excretion in SHRSPs but not in Wistar-Kyoto rats. Inhibition of Rac1 also reduced nicotinamide-adenine dinucleotide phosphate oxidase activity and ROS generation. In addition, Cu/Zn-superoxide dismutase activity in the NTS of SHRSPs was decreased compared with that of Wistar-Kyoto rats, despite the increased ROS generation. Overexpression of Cu/Zn-superoxide dismutase in the NTS decreased blood pressure and heart rate in SHRSPs. These results indicate that the activation of Rac1 in the NTS generates ROS via reduced nicotinamide-adenine dinucleotide phosphate oxidase in SHRSPs, and this mechanism might be important for the neuropathogenesis of hypertension in SHRSPs. Key Words: blood pressure Ⅲ heart rate Ⅲ sympathetic nervous system Ⅲ hypertension Ⅲ brain T here is accumulating evidence that reactive oxygen species (ROS) in the cardiovascular regulatory nuclei in the brain have a crucial role in blood pressure regulation in hypertension via modulating the sympathetic nervous system. 1-5 Reduced nicotinamide-adenine dinucleotide phosphate [NAD(P)H] oxidase is a major source of ROS in hypertension 6 and has a critical role in generating ROS in the brain. 2,5,7 Rac1 is a small G protein that is an important signaling molecule involved in integrating intracellular transduction pathways toward NAD(P)H oxidase activation. 2,8,9 Rac1 requires lipid modifications to migrate from the cytosol to the plasma membrane, which is a necessary step for activating the ROSgenerating NAD(P)H oxidase enzyme system. 8,9 The nucleus tractus solitarius (NTS) in the brain stem has an important role in cardiovascular regulation. 10 -16 The NTS receives afferent input from baroreceptors and chemoreceptors 12 and has reciprocal interconnections with other nuclei involved in central autonomic regulation. 17 In addition, the essential NAD(P)H oxidase subunit gp91 phox is present in somatodendritic and axonal profiles that contain angiotensin II (Ang II) subtype 1 receptors in the NTS, and Ang I...

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“…It is therefore intriguing that radioligand binding studies have consistently demonstrated either relatively very low levels of AT receptors in the adult rat striatum (Sirett et al, 1977;Mendelsohn et al, 1984) or levels often below the limits of detection (e.g. see Gehlert et al, 1991). Since it has been demonstrated that clear species differences exist with respect to the relative level of AT receptor density within the striatum (with relatively high levels of AT receptors in the human striatum; Allen et al, 1992;Barnes et al, 1993;MacGregor et al, 1995) and also that AT receptor densities display marked ontological variations (with relatively high levels during foetal and neonatal development; e.g.…”

Section: Stereotaxic Implantation Of Chronic Indwelling Guide Cannulaementioning

confidence: 99%

Ability of angiotensin II to modulate striatal dopamine release via the AT₁ receptor in vitro and in vivo

Brown

Steward

Jin

et al. 1996

British J Pharmacology

105

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1 The ability of angiotensin II to modulate dopamine release from rat striatal slices in vitro and in the intact rat striatum in vivo was assessed by the microdialysis technique.2 In slices of rat striatum, angiotensin II (0.1-1.0 gM) induced a concentration-related increase in endogenous dopamine release which was maximal (approximately 250% above basal levels) within the first 2-4 min of agonist application and subsequently declined to near

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Autoradiographic localization of subtypes of angiotensin II antagonist binding in the rat brain

Cited by 160 publications

References 35 publications

Angiotensin-II Is a Putative Neurotransmitter in Lactate-Induced Panic-Like Responses in Rats with Disruption of GABAergic Inhibition in the Dorsomedial Hypothalamus

Angiotensin-II Is a Putative Neurotransmitter in Lactate-Induced Panic-Like Responses in Rats with Disruption of GABAergic Inhibition in the Dorsomedial Hypothalamus

Inhibition of Rac1-Derived Reactive Oxygen Species in Nucleus Tractus Solitarius Decreases Blood Pressure and Heart Rate in Stroke-Prone Spontaneously Hypertensive Rats

Ability of angiotensin II to modulate striatal dopamine release via the AT₁ receptor in vitro and in vivo

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Autoradiographic localization of subtypes of angiotensin II antagonist binding in the rat brain

Cited by 160 publications

References 35 publications

Angiotensin-II Is a Putative Neurotransmitter in Lactate-Induced Panic-Like Responses in Rats with Disruption of GABAergic Inhibition in the Dorsomedial Hypothalamus

Angiotensin-II Is a Putative Neurotransmitter in Lactate-Induced Panic-Like Responses in Rats with Disruption of GABAergic Inhibition in the Dorsomedial Hypothalamus

Inhibition of Rac1-Derived Reactive Oxygen Species in Nucleus Tractus Solitarius Decreases Blood Pressure and Heart Rate in Stroke-Prone Spontaneously Hypertensive Rats

Ability of angiotensin II to modulate striatal dopamine release via the AT1 receptor in vitro and in vivo

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Ability of angiotensin II to modulate striatal dopamine release via the AT₁ receptor in vitro and in vivo