Brain and liver angiotensinogen messenger RNA in genetic hypertensive and normotensive rats.

Yongue, Brandon G.; Angulo, Jesús A.; McEwen, Bruce S.; Myers, Michael

doi:10.1161/01.hyp.17.4.485

Cited by 54 publications

(19 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In some pathological states (e.g., rats with heart failure), proinflammatory cytokines are increased in the hypothalamus and contribute to neurohumoral excitation by activating the brain RAS (23). Upregulation of the RAS in the brain has been reported in experimental and genetic models of hypertension (5,17,28,46). This study provides the groundwork for future investigations on the role of ANG-(1-12) and ANG II in the ARCN in different pathological states such heart failure and hypertension, including obesity-induced hypertension.…”

Section: Perspectivesmentioning

confidence: 99%

The hypothalamic arcuate nucleus: a new site of cardiovascular action of angiotensin-(1–12) and angiotensin II

Arakawa

Chitravanshi

Sapru

2011

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Arakawa H, Chitravanshi VC, Sapru HN. The hypothalamic arcuate nucleus: a new site of cardiovascular action of angiotensin-(1-12) and angiotensin II. Am J Physiol Heart Circ Physiol 300: H951-H960, 2011. First published December 24, 2010 doi:10.1152/ajpheart.01144.2010.-The hypothalamic arcuate nucleus (ARCN) has been reported to play a significant role in cardiovascular regulation. It has been hypothesized that the ARCN may be one of the sites of cardiovascular actions of angiotensins (ANGs). Experiments were carried out in urethaneanesthetized, artificially ventilated, adult male Wistar rats. The ARCN was identified by microinjections of N-methyl-D-aspartic acid (NMDA; 10 mM). Microinjections (50 nl) of ANG-(1-12) (1 mM) into the ARCN elicited increases in mean arterial pressure (MAP), heart rate (HR), and greater splanchnic nerve activity (GSNA). The tachycardic responses to ANG-(1-12) were attenuated by bilateral vagotomy. The cardiovascular responses elicited by ANG-(1-12) were attenuated by microinjections of ANG II type 1 receptor (AT1R) antagonists but not ANG type 2 receptor (AT2R) antagonist. Combined inhibition of ANG-converting enzyme (ACE) and chymase in the ARCN abolished ANG-(1-12)-induced responses. Microinjections of ANG II (1 mM) into the ARCN also increased MAP and HR. Inhibition of ARCN by microinjections of muscimol (1 mM) attenuated the pressor and tachycardic responses to intravenously administered ANG-(1-12) and ANG II (300 pmol/kg each). These results indicated that 1) microinjections of ANG-(1-12) into the ARCN elicited increases in MAP, HR, and GSNA; 2) HR responses were mediated via both sympathetic and vagus nerves; 3) AT1Rs, but not AT2Rs, in the ARCN mediated ANG-(1-12)-induced responses; 4) both ACE and chymase were needed to convert ANG-(1-12) to ANG II in the ARCN; and 5) ARCN plays a role in mediating the cardiovascular responses to circulating ANGs. blood pressure; heart rate; microinjection; N-methyl-D-aspartic acid; sympathetic nerve activity THE HYPOTHALAMIC ARCUATE NUCLEUS (ARCN) may play a significant role in cardiovascular regulation (10, 38). Consistent with this notion, we (31) have recently reported that chemical stimulation of the ARCN elicited increases in mean arterial pressure (MAP), heart rate (HR), and sympathetic nerve activity (SNA). These reports have provided a basis for investigations on different neurotransmitters and neuromodulators in the ARCN that may play a role in the regulation of cardiovascular function in normal and pathological states.A new endogenous angiotensin (ANG), ANG-(1-12), has recently been identified (30,44). Intravenous administration of this peptide has been reported to elicit an immediate pressor response in the rat, and this effect was blocked by prior administration of an ANG-converting enzyme (ACE) inhibitor or an ANG II type 1 receptor (AT 1 R) antagonist (30). These data indicated that in the periphery, ANG-(1-12) exerts its actions via a rapid conversion to ANG II (30). High concentrations of ANG-(1-12) have been reported in th...

show abstract

Section: Perspectivesmentioning

confidence: 99%

The hypothalamic arcuate nucleus: a new site of cardiovascular action of angiotensin-(1–12) and angiotensin II

Arakawa

Chitravanshi

Sapru

2011

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

show abstract

“…The obvious nature of the RAS as a candidate system for the etiology of hypertension has prompted a number of investigators to examine this system at the molecular biologic and molecular genetic level, and several important findings have resulted from these studies. First, the levels of mRNAs encoding renin, angiotensinogen, and angiotensinconverting enzyme (ACE) are significantly altered in some tissues of experimentally hypertensive and genetically hypertensive rats when compared with their normotensive counterparts (1)(2)(3)(4)(5). Second, centrally administered antisense oligonucleotides to angiotensinogen are effective in lowering blood pressure in spontaneously hypertensive rats (6).…”

Section: Introductionmentioning

confidence: 99%

Chronic hypertension and altered baroreflex responses in transgenic mice containing the human renin and human angiotensinogen genes.

Merrill¹,

Thompson²,

Carney³

et al. 1996

J. Clin. Invest.

170

192

View full text Add to dashboard Cite

We have generated a transgenic model consisting of both the human renin and human angiotensinogen genes to study further the role played by the renin-angiotensin system in regulating arterial pressure. Transgenic mice containing either gene alone were normotensive, whereas mice containing both genes were chronically hypertensive. Plasma renin activity and plasma angiotensin II levels were both markedly elevated in the double transgenic mice compared with either single transgenic or nontransgenic controls. The elevation in blood pressure caused by the human transgenes was independent of the genotype at the endogenous renin locus and was equal in mice homozygous for the Ren-1 c allele or in mice containing one copy each of Ren-1 c , Ren-1 d , or Ren-2. Chronic overproduction of angiotensin II in the double transgenic mice resulted in a resetting of the baroreflex control of heart rate to a higher pressure without significantly changing the gain or sensitivity of the reflex. Moreover, this change was not due to the effects of elevated pressure itself since angiotensin-converting enzyme inhibition had minimal effects on the baroreflex in spontaneously hypertensive BPH-2 control mice, which exhibit non-renindependent hypertension. This double transgenic model should provide an excellent tool for further studies on the mechanisms of hypertension initiated by the renin-angiotensin system. ( J. Clin. Invest. 1996. 97:1047-1055.)

show abstract

“…Existence of a local RAS in the CNS has been suggested, since all components of this system have been reported in the brain. In addition, several lines of evidence point to a contribution of an overactive brain RAS to the hypertensive state in spontaneously hypertensive rats, deoxycorticosterone acetate (DOCA) salt hypertensive rats, Dahl salt sensitive rats, and renal hypertensive rats (3)(4)(5)(6).…”

mentioning

confidence: 99%

Glia- and Neuron-specific Expression of the Renin-Angiotensin System in Brain Alters Blood Pressure, Water Intake, and Salt Preference

Morimoto

Cassell

Sigmund

2002

Journal of Biological Chemistry

108

124

View full text Add to dashboard Cite

The purpose of this study is to examine the regulation of blood pressure and fluid and electrolyte homeostasis in mice overexpressing angiotensin II (Ang-II) in the brain and to determine whether there are significant physiologic differences in Ang-II production in neurons or glia. Therefore, we generated and characterized transgenic mice overexpressing human renin (hREN) under the control of the glial fibrillary acidic protein (GFAP) promoter (GFAP-hREN) and synapsin-I promoter (SYN-hREN) and bred them with mice expressing human angiotensinogen (hAGT) under the control of the same promoters (GFAP-hAGT and SYN-hAGT). Both GFAP-hREN and SYN-hREN mice exhibited the highest hREN mRNA expression in the brain and had undetectable levels of hREN protein in the systemic circulation. In the brain of GFAP-hREN and SYN-hREN mice, hREN protein was observed almost exclusively in astrocytes and neurons, respectively. Transgenic mice overexpressing both hREN and hAGT transgenes in either glia or neurons were moderately hypertensive. In the gliatargeted mice, blood pressure could be corrected by intracerebroventricular injection of the Ang-II type 1 receptor antagonist losartan, and intravenous injection of a ganglion blocking agent, but not an arginine vasopressin V1 receptor antagonist, lowered blood pressure. These data suggest that stimulation of Ang-II type 1 receptors in the brain by Ang-II derived from local synthesis of renin and angiotensinogen can cause an elevation in blood pressure via a mechanism involving enhanced sympathetic outflow. Glia-and neuron-targeted mice also exhibited an increase in drinking volume and salt preference, suggesting that chronic overexpression of renin and angiotensinogen locally in the brain can result in hypertension and alterations in fluid homeostasis. The peptide angiotensin II (Ang-II)1 is the main circulating effector hormone of the renin-angiotensin system (RAS) and is able to act not only on peripheral vascular structures but also on the central nervous system (CNS) to increase blood pressure (BP) (1). Substantial evidence has accumulated that Ang-II has actions on the CNS including increasing sympathetic outflow, arginine vasopressin (AVP) release, water intake, and salt appetite (2). Existence of a local RAS in the CNS has been suggested, since all components of this system have been reported in the brain. In addition, several lines of evidence point to a contribution of an overactive brain RAS to the hypertensive state in spontaneously hypertensive rats, deoxycorticosterone acetate (DOCA) salt hypertensive rats, Dahl salt sensitive rats, and renal hypertensive rats (3-6).Despite numerous studies demonstrating the important cardiovascular effects of Ang-II or Ang-II receptor antagonists injected into the brain, it remains unclear whether RAS components synthesized in the brain, in particular renin and angiotensinogen (AGT), have an important role in the local synthesis of Ang-II. In the brain, AGT expression is localized mainly in astrocytes (glia) (7,8). To determine whether l...

show abstract

Brain and liver angiotensinogen messenger RNA in genetic hypertensive and normotensive rats.

Cited by 54 publications

References 32 publications

The hypothalamic arcuate nucleus: a new site of cardiovascular action of angiotensin-(1–12) and angiotensin II

The hypothalamic arcuate nucleus: a new site of cardiovascular action of angiotensin-(1–12) and angiotensin II

Chronic hypertension and altered baroreflex responses in transgenic mice containing the human renin and human angiotensinogen genes.

Glia- and Neuron-specific Expression of the Renin-Angiotensin System in Brain Alters Blood Pressure, Water Intake, and Salt Preference

Contact Info

Product

Resources

About