Lateral parabrachial nucleus and angiotensin II-induced hypertension.

Fink, Gregory D.; Pawloski, C. M.; Ohman, Lynne E.; Haywood, Joseph R.

doi:10.1161/01.hyp.17.6.1177

Cited by 26 publications

(23 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, the LPBN has also been described as playing an integrative role in relaying baroreceptor information to forebrain regions, and bilateral ablation of the LPBN in rats has also prevented the development of sustained Ang II-induced hypertension. 22 Although further investigation is required, these data suggest that neurons located within brain stem regions and in the LPBN may play a role in regulating acute but not chronic Ang II-induced hypertension via an ascending baroreceptive pathway.…”

Section: Discussionmentioning

confidence: 93%

Fos-Related Antigen Immunoreactivity After Acute and Chronic Angiotensin II–Induced Hypertension in the Rabbit Brain

Davern

Head

2007

Hypertension

View full text Add to dashboard Cite

Abstract-Several brain regions are proposed as contributing to chronic sympatho-excitatory effects of elevated circulating angiotensin II. However, earlier c-Fos studies have been limited to acute angiotensin II exposure. This study aims to determine brain regions responding with chronic elevated angiotensin II. Rabbits were administered angiotensin II (50 ng/kg per minute) or saline for 3 hours, 3 days, or 14 days. Basal mean arterial pressure was 71Ϯ2 mm Hg and increased 23Ϯ2 mm Hg, 32Ϯ4 mm Hg, and 22Ϯ2 mm Hg for 3 hours, 3 days, and 14 days, respectively, with angiotensin II infusion. Neuronal activation was detected using Fos-related antigens, which recognizes all of the known members of the Fos family. Neurons located in the amygdala and area postrema were activated transiently after acute infusion of angiotensin II but were not responsive by days 3 or 14. Neurons located in the nucleus of the solitary tract, caudal ventrolateral medulla, and lateral parabrachial nucleus were activated for Յ3 days after infusion of angiotensin II but were not responsive by day 14, which is consistent with their role in response to baroreceptor pathways that reset with sustained hypertension. The vascular organ of the lamina terminalis and subfornical organ showed sustained but diminishing activation over the 14-day period. However, the downstream hypothalamic nuclei that receive inputs from these nuclei, the paraventricular, supraoptic, and arcuate nuclei, showed marked sustained activation. These findings suggest that there is desensitization of circumventricular organs but sensitization of neurons in hypothalamic regions to long-term angiotensin II infusion. Key Words: angiotensin II Ⅲ chronic hypertension Ⅲ Fos-related antigen Ⅲ immunohistochemistry Ⅲ rabbit brain A lthough renal hypertension is thought to be largely volume dependent, there is growing evidence to suggest that sympathetic nerve activity in hypertensive animals and also in human forms of the disease is likely to be increased. 1 A greater depressor response to ganglion blockade has been observed in angiotensin II (Ang II)-infused hypertensive rats 2 and renal wrap hypertensive rabbits. 3 In renovascular hypertensive patients, noradrenaline spillover is elevated. 4 Thus, it has been suggested that there are 2 distinct phases of Ang II-induced hypertension, an initial hypertension because of Ang II-mediated vasoconstriction that is replaced by a longer-term, neurogenic component. 2,3,5 Even so, the expected greater sympathetic activity in renovascular hypertension has been surprisingly difficult to confirm because of the use of indirect measures, which have yielded conflicting findings. 6,7 Moreover, recent studies have suggested that baroreceptor mechanisms inhibit sympathetic activity not only acutely but over several days, preventing sympathetic activation. 8,9 This hypothesis questions whether baroreceptors reset completely and suggests that, if they do not, then they may contribute to blood pressure regulation in the long term. These studies are limited ...

show abstract

Section: Discussionmentioning

confidence: 93%

Fos-Related Antigen Immunoreactivity After Acute and Chronic Angiotensin II–Induced Hypertension in the Rabbit Brain

Davern

Head

2007

Hypertension

View full text Add to dashboard Cite

show abstract

“…19 We have previously shown that the fluorescein isothiocyanate-labeled AS-ODN was taken up into the tissue around the third or lateral ventricle by intracerebroventricular injection 15 and that AS-ODN-AT 1 R decreased brain angiotensin receptors by use of membrane binding and autoradiographic analysis. 20 Other nuclei of the brain such as the lateral parabrachial nucleus 21 and the area postrema 22 have been reported to be important in Ang II-induced hypertensive rats. Therefore, the brain stem as a site of action cannot be ruled out because the AS-ODN injected in the cerebral ventricle may not have reached brain stem sites in sufficient amounts.…”

Section: Kagiyama Et Al Central Ras Inhibition In Chronic 2k1c 373mentioning

confidence: 99%

Antisense Inhibition of Brain Renin-Angiotensin System Decreased Blood Pressure in Chronic 2-Kidney, 1 Clip Hypertensive Rats

et al. 2001

View full text Add to dashboard Cite

Abstract-The systemic renin-angiotensin system (RAS) plays an important role in blood pressure (BP) regulation during the development of 2-kidney, 1 clip (2K1C) hypertension. Its contributions decrease with time after constriction of the renal artery. During the chronic phase, the peripheral RAS returns to normal, but the hypertension is sustained for months. We hypothesized that in this phase the brain RAS contributes to the maintenance of high BP. To test the hypothesis, we studied the role of brain RAS by decreasing the synthesis of angiotensinogen (AGT) and the angiotensin II (Ang II) type 1a receptor (AT 1 R) with intracerebroventricular injections of antisense oligonucleotides (AS-ODNs). The response of systolic BP (SBP) to AS-ODNs to AGT mRNA was studied in 2K1C rats at 6 months after clipping, and the response to AS-ODNs to AT 1 R mRNA was studied at 10 months after clipping. Key Words: rats Ⅲ renin-angiotensin system Ⅲ brain Ⅲ hypertension, 2K1C Ⅲ antisense T he renin-angiotensin system (RAS) plays an important role in blood pressure (BP) regulation during the development of renovascular hypertension. 1 In the rat model of unilateral renovascular hypertension (the 2-kidney, 1 clip Goldblatt [2K1C] hypertensive rat), renal stenosis elevates the RAS. The contributions of RAS in this model vary depending on the time after constriction of the renal artery. 2 In the acute phase of 2K1C hypertension, plasma renin activity rises, and the increase in BP is RAS dependent. Both plasma renin activity and plasma angiotensin II (Ang II) concentrations normalize in the chronic phase despite the continued high BP. To explain the antihypertensive effects of ACE inhibitors when the circulating RAS is not overtly activated, the concept of tissue RAS has been used. It is proposed that in 2K1C hypertension, the RAS in various tissues is activated, and the products act in a paracrine fashion and are not detectable in plasma. 3,4 An activation of tissue RAS in the acute phase of 2K1C hypertension has been extensively discussed. [3][4][5][6][7][8][9] By contrast, few studies have examined the mechanism of maintained hypertension in the chronic phase, 9,10 although clinically, this is much more relevant. Most renovascular hypertensive patients present with chronic high BP. We have shown that inhibiting the brain RAS in adult spontaneously hypertensive rats (SHR) significantly reduces hypertension. 11 Baltatu et al 12 have reported that the transgenic rat [TGR(ASrAoGEN)], which has permanent inhibition of brain-specific angiotensinogen (AGT) synthesis, shows a reduction of hypertension induced by a low-dose of Ang II. Therefore, we hypothesize that as the 2K1C hypertension progresses chronically, the brain RAS contributes to elevated BP in the absence of peripheral RAS elevation.To test this hypothesis, we used antisense (AS) oligodeoxynucleotides (ODNs), which we previously designed to inhibit components of the brain RAS, including AGT mRNA and Ang II type 1a receptor (AT 1 R) mRNA. 13-15 AS-ODN has some advantages over drugs:...

show abstract

“…Arguments are based on the elimination of the hypertensive effect of Ang II by ablation of area postrema 3 or lateral parabrachial nucleus. 4 Furthermore, the hypertensive effect of subpressor doses of Ang II can be inhibited by central sympathoinhibitors, 5 ganglionic blockers, 6 nonselective ␣-blockade, 7 or renal denervation, 8 supporting a neurogenic pressor mechanism.The role of the brain RAS in the central control of cardiovascular homeostasis and pathophysiology is well documented. 9 Complementing and interacting with the endocrine RAS, the brain RAS is postulated to contribute to the pathology of hypertension and cardiovascular diseases.…”

mentioning

confidence: 99%

mentioning

confidence: 99%

The Brain Renin-Angiotensin System Modulates Angiotensin II–Induced Hypertension and Cardiac Hypertrophy

et al. 2000

View full text Add to dashboard Cite

Abstract-The potential involvement of the brain renin-angiotensin system in the hypertension induced by subpressor doses of angiotensin II was tested by the use of newly developed transgenic rats with permanent inhibition of brain angiotensinogen synthesis [TGR(ASrAOGEN)]. Basal systolic blood pressure monitored by telemetry was significantly lower in TGR(ASrAOGEN) than in Sprague-Dawley rats (parent strain) (122.5Ϯ1.5 versus 128.9Ϯ1.9 mm Hg, respectively; PϽ0.05). The increase in systolic blood pressure induced by 7 days of chronic angiotensin II infusion was significantly attenuated in TGR(ASrAOGEN) in comparison with control rats (29.8Ϯ4.2 versus 46.3Ϯ2.5 mm Hg, respectively; PϽ0.005). Moreover, an increase in heart/body weight ratio was evident only in Sprague-Dawley (11.1%) but not in TGR(ASrAOGEN) rats (2.8%). In contrast, mRNA levels of atrial natriuretic peptide (ANP) and collagen III in the left ventricle measured by ribonuclease protection assay were similarly increased in both TGR(ASrAOGEN) (ANP, ϫ2.5; collagen III, ϫ1.8) and Sprague-Dawley rats (ANP, ϫ2.4; collagen III, ϫ2) as a consequence of angiotensin II infusion. Thus, the expression of these genes in the left ventricle seems to be directly stimulated by angiotensin II. However, the hypertensive and hypertrophic effects of subpressor angiotensin II are at least in part mediated by the brain renin-angiotensin system. Key Words: renin-angiotensin system Ⅲ collagen Ⅲ angiotensin II Ⅲ hypertrophy Ⅲ atrial natriuretic peptide T he renin-angiotensin system (RAS) is acknowledged to play an important role in the pathophysiology of hypertension and cardiovascular diseases. Since tissue RASs have been postulated, local formation of angiotensin II (Ang II) is consistently invoked to explain that RAS inhibitors can exert beneficial effects in cardiovascular diseases, even in the absence of Ang II plasma levels that directly increase blood pressure (BP). 1 The mechanisms by which increases in plasma Ang II can induce an increase in BP in these situations are still not clearly defined. One experimental animal model designed to mimic human hypertension that is often used to obtain insights regarding its pathophysiological mechanisms is attained by chronic infusion (days to weeks) of subpressor doses of Ang II. 2 Infused doses of Ang II up to 250 ng/kg per minute SC that do not produce direct vasoconstriction are described as "subpressor" or "slow pressor" and can induce a gradual increase of BP. Several studies have indicated that the central nervous system is involved in the effects of the subpressor Ang II. Arguments are based on the elimination of the hypertensive effect of Ang II by ablation of area postrema 3 or lateral parabrachial nucleus. 4 Furthermore, the hypertensive effect of subpressor doses of Ang II can be inhibited by central sympathoinhibitors, 5 ganglionic blockers, 6 nonselective ␣-blockade, 7 or renal denervation, 8 supporting a neurogenic pressor mechanism.The role of the brain RAS in the central control of cardiovascular homeostasis and p...

show abstract

Lateral parabrachial nucleus and angiotensin II-induced hypertension.

Cited by 26 publications

References 26 publications

Fos-Related Antigen Immunoreactivity After Acute and Chronic Angiotensin II–Induced Hypertension in the Rabbit Brain

Fos-Related Antigen Immunoreactivity After Acute and Chronic Angiotensin II–Induced Hypertension in the Rabbit Brain

Antisense Inhibition of Brain Renin-Angiotensin System Decreased Blood Pressure in Chronic 2-Kidney, 1 Clip Hypertensive Rats

The Brain Renin-Angiotensin System Modulates Angiotensin II–Induced Hypertension and Cardiac Hypertrophy

Contact Info

Product

Resources

About