The Brain Renin-Angiotensin System And Salt-Sensitive Hypertension

Veerasingham, Shereeni J.; Leenen, Frans H. H.

doi:10.1007/978-1-4615-5743-2_2

Cited by 4 publications

(4 citation statements)

References 83 publications

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“…19 Most of the central physiological effects of Ang II are mediated through AT 1 -receptor stimulation. 20 Whereas chronic losartan abolishes the acute responses to intracerebroventricular Ang II, the vehicle (aCSF) per se administered chronically 3,4 or acutely 8 has no effects on the responses to Ang II. Therefore, similar to acute intracerebroventricular administration of ouabain, 8 a chronic increase in brain ouabain 10 as a result of chronic subcutaneous administration of ouabain appears to activate brain pathways involving AT 1 receptors, leading to sympathoexcitation and hypertension.…”

Section: Ouabain Activates Brain Rasmentioning

confidence: 40%

Brain Renin-Angiotensin System and Ouabain-Induced Sympathetic Hyperactivity and Hypertension in Wistar Rats

Huang

Leenen

1999

Hypertension

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Abstract-In Dahl salt-sensitive rats on a high salt diet or normotensive rats with chronic central infusion of sodium, increased brain "ouabain" results in sympathetic hyperactivity and hypertension, possibly by activating the brain renin-angiotensin system. In the present study, we tested whether the hypertension caused by exogenous ouabain also depends on activation of brain renin-angiotensin system. In Wistar rats, ouabain (50 g/d) was infused subcutaneously for 14 days with the use of osmotic minipumps. Concomitantly, in one group, the angiotensin II type 1 receptor blocker losartan (1 mg/kg per day) was infused intracerebroventricularly. On day 15, mean arterial pressure, heart rate, central venous pressure, and renal sympathetic nerve activity were recorded in conscious rats at rest and in response to air-jet stress, intracerebroventricular injection of the ␣ 2 -agonist guanabenz (25 and 75 g) or angiotensin II (30 ng), acute volume expansion, and ramp changes of blood pressure by Ϯ50 mm Hg with phenylephrine and nitroprusside. Compared with control rats, in rats treated with ouabain, resting mean arterial pressure was significantly increased (111Ϯ4 versus 93Ϯ3 mm Hg; PϽ0.05), and increases or decreases in mean arterial pressure, heart rate, and renal sympathetic nerve activity in response to air stress or guanabenz were enhanced significantly. These effects of ouabain were prevented when losartan was given concomitantly. Maximal slopes of arterial baroreflex control of renal sympathetic nerve activity and heart rate tended to be decreased in ouabain-treated versus control rats and were significantly increased in ouabain-treated rats with versus without losartan. No differences in cardiopulmonary baroreflex function were detected. It seems that by day 14 to 15, the central effect of ouabain on baroreflex control prevails over its peripheral sensitizing effect on baroreceptors, leading to a tendency of desensitization. These results indicate that chronic administration of ouabain activates the brain renin-angiotensin system, resulting in decreased sympathoinhibition and increased sympathoexcitation, impairment of baroreflex function, and hypertension. Key Words: baroreflex Ⅲ renal nerves Ⅲ stress, air-jet Ⅲ guanabenz Ⅲ renin-angiotensin system I ncreased sympathetic activity mediates salt-sensitive hypertension in spontaneously hypertensive rats (SHR) and Dahl salt-sensitive rats. 1,2 The sympathoexcitatory and pressor effects of high salt are prevented by either chronic intracerebroventricular administration of an angiotensin II type 1 (AT 1 ) receptor antagonist 3,4 or antibody Fab fragments, 3,4 binding ouabain and endogenous ouabainlike activity ("ouabain"). 5,6 Therefore, in Dahl salt-sensitive rats and SHR on high salt, both brain angiotensin II (Ang II) and brain "ouabain" contribute to sympathetic hyperactivity and hypertension. 3,4 We postulated that brain "ouabain" exerts its effects possibly by activation of the brain renin angiotensin system (RAS), 3,4,7 since blockade of brain AT 1 receptors bl...

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Section: Ouabain Activates Brain Rasmentioning

confidence: 40%

Brain Renin-Angiotensin System and Ouabain-Induced Sympathetic Hyperactivity and Hypertension in Wistar Rats

Huang

Leenen

1999

Hypertension

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“…The renin–angiotensin system (RAS) is one of the major systems in the regulation of cardiovascular function and fluid homeostasis. A complete RAS exists in the brain and comprises all necessary precursors and enzymes required for formation and metabolism of its components (Veersingham and Raizada 2003; Saavedra 2005) . Within the brain, angiotensin (Ang) II contributes to cardiovascular regulation via its action at various hypothalamic and medullary areas resulting in elevated blood pressure, augmented drinking behavior, attenuation of the baroreflex, enhancement of sympathetic outflow, and augmented vasopressin release (Veersingham and Raizada 2003; Saavedra 2005).…”

mentioning

confidence: 99%

Angiotensin‐(1–7) through AT₂ receptors mediates tyrosine hydroxylase degradation via the ubiquitin–proteasome pathway

Verrilli

Pirola

Pascual

et al. 2009

Journal of Neurochemistry

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Hypothalamic norepinephrine (NE) release regulates arterial pressure by altering sympathetic nervous system activity. Because angiotensin (Ang) (1–7) decreases hypothalamic NE release and this effect may be correlated with a diminished NE synthesis, we hypothesize that Ang‐(1–7) down‐regulates tyrosine hydroxylase (TH), the rate‐limiting enzyme in catecholamines biosynthesis. We investigated the effect of Ang‐(1–7) on centrally TH activity and expression. TH activity was evaluated by the release of tritiated water from 3H‐l‐tyrosine. TH expression and phosphorylation were determined by western blot. Hypothalami from normotensive or spontaneously hypertensive rats pre‐incubated with Ang‐(1–7) showed a significant decrease in TH specific activity. Ang‐(1–7) caused a decrease in TH phosphorylation at Ser19 and Ser40 residues. The heptapeptide induced a decrease in TH expression that was blocked by an AT2 receptor antagonist and not by an AT1 or Mas receptor antagonist, suggesting the involvement of AT2 receptors. The proteasome inhibitor MG132 blocked the Ang‐(1–7)‐mediated TH reduction. In addition, Ang‐(1–7) increased the amount of TH–ubiquitin complexes, indicating that the Ang‐(1–7)‐mediated TH degradation involves ubiquitin conjugation prior to proteasome degradation. We conclude that Ang‐(1–7) down‐regulates TH activity and expression centrally leading to a decrease in the central NE system activity.

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“…In contrast to the well-understood circulatory RAS, a satisfactory definition of a local RAS is still elusive. The existence of all components of the system within tissues that are targets for angiotensins is now well accepted (2,11,15,17,29,34,38). However, the presence of all components of the RAS in the same cells would provide an attractive model to study its intracellular organization and regulation (26).…”

Section: Discussionmentioning

confidence: 99%

“…sympathetic ganglia, kidneys, heart, blood vessel walls, and eyes (2,11,15,34,38). However, where and how angiotensins are locally formed is still controversial.…”

mentioning

confidence: 99%

Presence of cellular renin-angiotensin system in chromaffin cells of bovine adrenal medulla

Wang

Slembrouck

Tan

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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The presence of a local renin-angiotensin system has been established in organs that serve as angiotensin targets. In this study, the expression of angiotensinogen mRNA and subcellular localization of renin, angiotensin-converting enzyme, and angiotensin II were investigated in bovine adrenal medullary cells in primary culture. By light microscopy, expression of angiotensinogen mRNA, immunoreactive renin, angiotensin-converting enzyme, and angiotensin II were readily detectable only in the chromaffin cells. The density distribution of renin and angiotensin II in sucrose gradients suggested a concentration in chromaffin granules, a localization directly confirmed by immunoelectron microscopy. Reverse transcriptase-polymerase chain reaction and sequencing confirmed the expression of angiotensinogen in bovine chromaffin cells and the adrenal medulla. In addition, in vitro autoradiography indicated that both angiotensin-converting enzyme and angiotensin type 1 receptors were present in the adrenal medulla. These results provide the first direct evidence that chromaffin cells in the adrenal medulla are not only the target for angiotensin but should also be considered as potential local angiotensin-generating and -storing cells.

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The Brain Renin-Angiotensin System And Salt-Sensitive Hypertension

Cited by 4 publications

References 83 publications

Brain Renin-Angiotensin System and Ouabain-Induced Sympathetic Hyperactivity and Hypertension in Wistar Rats

Brain Renin-Angiotensin System and Ouabain-Induced Sympathetic Hyperactivity and Hypertension in Wistar Rats

Angiotensin‐(1–7) through AT₂ receptors mediates tyrosine hydroxylase degradation via the ubiquitin–proteasome pathway

Presence of cellular renin-angiotensin system in chromaffin cells of bovine adrenal medulla

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The Brain Renin-Angiotensin System And Salt-Sensitive Hypertension

Cited by 4 publications

References 83 publications

Brain Renin-Angiotensin System and Ouabain-Induced Sympathetic Hyperactivity and Hypertension in Wistar Rats

Brain Renin-Angiotensin System and Ouabain-Induced Sympathetic Hyperactivity and Hypertension in Wistar Rats

Angiotensin‐(1–7) through AT2 receptors mediates tyrosine hydroxylase degradation via the ubiquitin–proteasome pathway

Presence of cellular renin-angiotensin system in chromaffin cells of bovine adrenal medulla

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Angiotensin‐(1–7) through AT₂ receptors mediates tyrosine hydroxylase degradation via the ubiquitin–proteasome pathway