Baroreceptor reflex regulation in anesthetized transgenic rats with low glia-derived angiotensinogen

Sakima, Atsushi; Averill, David B.; Каспер, С.; Jackson, LaRhonda M.; Ganten, Detlev; Ferrario, Carlos M.; Gallagher, Patricia E.; Diz, Debra I.

doi:10.1152/ajpheart.00984.2006

Cited by 36 publications

(79 citation statements)

References 58 publications

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“…Both methods show that AGT is widely expressed in astrocytes (32,131), and in those cells, was localized in the nucleus (122). Genetic deletion of glial-specific AGT lowers arterial pressure in double transgenic mice expressing both human renin and human AGT (121), and antisense inhibition of glial AGT in rats results is altered baroreflex regulation and increased exercise tolerance (43,119). AGT is also expressed in neurons, specifically within nuclei of the brain important for cardiovascular (CV) regulation, such as the SFO, RVLM, PB, and PVN (58,136,150).…”

Section: Localization Of Ras Components Required For Ang II Productionmentioning

confidence: 99%

Mechanisms of brain renin angiotensin system-induced drinking and blood pressure: importance of the subfornical organ

Coble¹,

Grobe

Johnson³

et al. 2015

American Journal of Physiology-Regulatory, Integrative and Comp

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Coble JP, Grobe JL, Johnson AK, Sigmund CD. Mechanisms of brain renin angiotensin system-induced drinking and blood pressure: importance of the subfornical organ. Am J Physiol Regul Integr Comp Physiol 308: R238 -R249, 2015. First published December 17, 2014 doi:10.1152/ajpregu.00486.2014.-It is critical for cells to maintain a homeostatic balance of water and electrolytes because disturbances can disrupt cellular function, which can lead to profound effects on the physiology of an organism. Dehydration can be classified as either intra-or extracellular, and different mechanisms have developed to restore homeostasis in response to each. Whereas the renin-angiotensin system (RAS) is important for restoring homeostasis after dehydration, the pathways mediating the responses to intra-and extracellular dehydration may differ. Thirst responses mediated through the angiotensin type 1 receptor (AT 1R) and angiotensin type 2 receptors (AT 2R) respond to extracellular dehydration and intracellular dehydration, respectively. Intracellular signaling factors, such as protein kinase C (PKC), reactive oxygen species (ROS), and the mitogen-activated protein (MAP) kinase pathway, mediate the effects of central angiotensin II (ANG II). Experimental evidence also demonstrates the importance of the subfornical organ (SFO) in mediating some of the fluid intake effects of central ANG II. The purpose of this review is to highlight the importance of the SFO in mediating fluid intake responses to dehydration and ANG II.angiotensin; blood pressure; barin; fluid; renin FLUID BALANCE is crucial for the homeostasis and survival of organisms because they have to properly maintain fluid and electrolyte concentrations for the normal function of all cells. Fluid balance can go awry in pathological states such as in chronic kidney disease and diabetes. Among its many roles in maintaining homeostasis, the renin-angiotensin system (RAS) is an important regulator of fluid balance. The RAS achieves this through the actions of its main effector peptide, angiotensin II (ANG II) through the ANG II type 1 (AT 1 R) and type 2 (AT 2 R) receptors. Activation of AT 1 R by blood-borne ANG II in target tissues causes increases in sodium and water retention, arginine vasopressin (AVP), and aldosterone release, vasoconstriction, increased sympathetic nervous system activity, and increased fluid intake. ANG II is produced by the consecutive enzymatic action of renin on its substrate angiotensinogen (AGT) and by angiotensin-converting enzyme (ACE) on its substrate angiotensin I (ANG I). The renin-AGT cleavage step is generally the rate-limiting step in the production of ANG II, and this is certainly true in the brain where the amount of renin is limiting. The RAS exists in two forms: a circulatory form where ANG II acts as an endocrine factor, and a tissue-specific form, where local production of ANG II acts in an autocrine or paracrine manner to induce AT 1 R signaling on ANG II producing or nearby cells (75). Intracrine, or intracellular forms of the RAS, hav...

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Section: Localization Of Ras Components Required For Ang II Productionmentioning

confidence: 99%

Mechanisms of brain renin angiotensin system-induced drinking and blood pressure: importance of the subfornical organ

Coble¹,

Grobe

Johnson³

et al. 2015

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Electrophysiological studies in transgenic rats have characterized the electrical phenotype of the heart 3,4) but little is known regarding the impact of experimental conditions or models on the outcome of such studies.…”

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confidence: 99%

Inhalation Anesthesia Is Preferable for Recording Rat Cardiac Function Using an Electrocardiogram

Murakami

Niwa

Kushikata

et al. 2014

Biological & Pharmaceutical Bulletin

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The effects of inhalation anesthesia (2% isoflurane, sevoflurane, or enflurane) and intraperitoneal anesthesia with pentobarbital (65 mg/kg) were compared in rats using an electrocardiogram (ECG) and determination of blood oxygen saturation (SPO 2 ) levels. Following inhalation anesthesia, heart rate (HR) and SPO 2 were acceptable while pentobarbital anesthesia decreased HR and SPO 2 significantly. This indicates that inhalation anesthesia is more preferable than pentobarbital anesthesia when evaluating cardiovascular factors. Additionally, pentobarbital significantly increased HR variability (HRV), suggesting a regulatory effect of pentobarbital on the autonomic nervous system, and resulted in a decreased response of the baro-reflex system. Propranolol or atropine had limited effects on ECG recording following pentobarbital anesthesia. Taken together, these data suggest that inhalation anesthesia is suitable for conducting hemodynamic analyses in the rat.

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“…7 Consistent with expression of Aogen mRNA in neurons of the paraventricular nucleus (PVN), neuronal Ang II and Ang-(1-7) are preserved in PVN of these animals compared with SD rats. 8 Functionally, conscious adult ASrAOGEN rats (3 to 5 months) have enhanced baroreceptor 9 and chemoreceptor 10 reflexes and lower resting mean AP (MAP) compared with age-matched SD rats. 4,11 Solitary tract nucleus (NTS) blockade of Ang II type 1 (AT 1 ) receptors has no effect on BRS, whereas blockade of Ang-(1-7) receptors impairs BRS in younger ASrAOGEN rats, suggesting a glial source of Aogen for Ang II and a nonglial source for Ang-(1-7) for modulating BRS for control of HR.…”

mentioning

confidence: 99%

“…4,11 Solitary tract nucleus (NTS) blockade of Ang II type 1 (AT 1 ) receptors has no effect on BRS, whereas blockade of Ang-(1-7) receptors impairs BRS in younger ASrAOGEN rats, suggesting a glial source of Aogen for Ang II and a nonglial source for Ang-(1-7) for modulating BRS for control of HR. 10 A paradoxical enhanced response to cardiac vagal afferent chemosensitive fiber acti-vation (CVA) and elevated resting MAP occurs under anesthesia compared with SD rats. 10 The elevated MAP in anesthetized ASrAOGEN rats was reversed by blockade of either AT 1 or Ang-(1-7) receptors.…”

mentioning

confidence: 99%

Modulation of Reflex Function by Endogenous Angiotensins in Older Transgenic Rats With Low Glial Angiotensinogen

et al. 2008

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Abstract-Age-related impairments in baroreflex sensitivity in Sprague-Dawley rats are associated with low solitary tract nucleus content of angiotensin-(1-7). However, transgenic rats with low-brain angiotensinogen resulting from glial overexpression of an antisense oligonucleotide to angiotensinogen (ASrAOGEN) are spared age-related declines in cardiovascular function characteristic of Sprague-Dawley rats. We examine whether cardiovascular and reflex actions of angiotensin-(1-7) persist in the solitary tract nucleus of older (16 to 22 months) ASrAOGEN rats. Baroreflex sensitivity for control of heart rate and chemosensitive vagal afferent activation in response to phenylbiguanide were measured before and after bilateral microinjection of the angiotensin II type 1 receptor antagonist candesartan and angiotensin-(1-7) receptor antagonist (D-Ala 7 )-angiotensin-(1-7) in urethane/chloralose-anesthetized rats. In older anesthetized ASrAOGEN rats, candesartan had no effect, whereas (D-Ala 7 )-angiotensin-(1-7) significantly reduced baroreflex sensitivity (1.80Ϯ0.43 versus 0.50Ϯ0.17 ms/mm Hg). Phenylbiguanide responses were attenuated by injection of candesartan (Ϫ79Ϯ6 versus Ϫ55Ϯ12 mm Hg and Ϫ277Ϯ12 versus Ϫ156Ϯ27 bpm; PϽ0.05). In addition, resting blood pressure was reduced by injection of candesartan or (D-Ala 7 )-angiotensin-(1-7). Within the solitary tract nucleus of older ASrAOGEN rats, it appears that glial angiotensinogen is the main source of angiotensin II attenuation of baroreflex sensitivity; endogenous angiotensin-(1-7) from nonglial sources enhances baroreflex sensitivity; nonglial sources of angiotensin II contribute to chemosensitive vagal afferent activation; and receptors for both peptides modulate resting arterial pressure under anesthesia. These results suggest a novel mechanism for the preservation of baroreflex sensitivity during aging.

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Baroreceptor reflex regulation in anesthetized transgenic rats with low glia-derived angiotensinogen

Cited by 36 publications

References 58 publications

Mechanisms of brain renin angiotensin system-induced drinking and blood pressure: importance of the subfornical organ

Mechanisms of brain renin angiotensin system-induced drinking and blood pressure: importance of the subfornical organ

Inhalation Anesthesia Is Preferable for Recording Rat Cardiac Function Using an Electrocardiogram

Modulation of Reflex Function by Endogenous Angiotensins in Older Transgenic Rats With Low Glial Angiotensinogen

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