Regulatory role of brain angiotensins in the control of physiological and behavioral responses

Wright, John W.; Harding, Joseph W.

doi:10.1016/0165-0173(92)90018-h

Cited by 269 publications

(138 citation statements)

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“…Angiotensin-induced thirst is primarily mediated in the OVLT, subfornical organ, and median preoptic nucleus, and angiotensin-induced sodium appetite originates in the OVLT and median preoptic nucleus, where central osmoreceptors function to maintain constant extracellular osmotic pressure (2,38,39). It is tempting to speculate that increased concentration of Ang-II in these areas may be involved in the mechanism of altered behavior in these mice.…”

Section: Discussionmentioning

confidence: 99%

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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

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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...

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Section: Discussionmentioning

confidence: 99%

“…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.…”

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

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“…Birth weight is in turn inversely associated with chronic disease in later life (Godfrey and Barker, 2000), with lower birth weight related to higher blood pressure (Godfrey and Barker, 2000;Law et al, 2002). Blood pressure and sodium-directed behavior both are components of overall cardiovascular homeostasis, and share a number of common physiologic controls (Wright and Harding, 1992;Johnson et al, 1999). Thus, it is possible that the association between birth weight and blood pressure might be mediated in part by prenatal influences on regulatory mechanisms related to perception of or response to salty taste.…”

Section: Introductionmentioning

confidence: 99%

Salty taste acceptance by infants and young children is related to birth weight: longitudinal analysis of infants within the normal birth weight range

2005

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Background: Birth weight and sodium intake are both associated with risk for hypertension. It is not known whether birth weight influences response to salty taste. Objective: To assess the relationship between birth weight and salty taste acceptance of infants and young children. Design: Acceptance of salty taste was assessed at 2 (n ¼ 80) and 6 (n ¼ 76) months in infants (birth weight 42.5 kg) enrolled in a prospective cohort study. Acceptance was expressed as proportional intake following 1-min ingestion tests with water and salt solutions (0.17 and 0.34 mol/l NaCl, in water). Birth weight was obtained by maternal report. Questionnaires completed by mothers and food-ranking procedures performed by children evaluated salt liking and preference in a subset (n ¼ 38) of subjects at preschool age (36 or 48 months). Setting: Nonprofit basic research institute in Philadelphia, PA, USA. Results: Regression analysis revealed significant negative associations between birth weight and acceptance of salty taste at 2 months (0.17 mol/l, Po0.0001; 0.34 mol/l, Po0.01) but not at 6 months. Relationships were not affected by adjustment for potential confounders. In preschoolers, greater liking of (Po0.05) and preference for (Po0.01) salty foods was associated with lower birth weight in simple, but not adjusted, models. Conclusion: Measures related to salty taste preference were inversely related to birth weight over the first 4 years of life. Additional studies should substantiate these findings and explore whether early response to salty taste predicts future sodium intake, blood pressure, or other public health-related outcomes.

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“…13 Acting on the brain, Ang II induces fluid and salt ingestion, modulates neuroendocrine systems, including vasopressin and corticotropin releasing factor release, and interacts with the autonomic control of the cardiovascular system to influence blood pressure. 3,14,15 In many instances, these effects are complementary to those of the systemic peptide on peripheral target organs. Thus, systematic Ang II affects the brain through AT 1 receptors located in the circumventricular organs, regions with a deficient blood brain barrier.…”

Section: Actions Of Ang IImentioning

confidence: 99%

“…3,14,15 In many instances, these effects are complementary to those of the systemic peptide on peripheral target organs. Thus, systematic Ang II affects the brain through AT 1 receptors located in the circumventricular organs, regions with a deficient blood brain barrier.…”

mentioning

confidence: 99%

Bioactive angiotensin peptides

et al. 1998

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Angiotensin II is recognised as the principle active peptide of the renin-angiotensin system, exerting effects on fluid and electrolyte homeostasis, and cardiovascular control including neural and long term trophic effects. However, recent studies indicate that other angiotensin peptides such as angiotensin III, angiotensin II (1-7) and angiotensin IV, may have specific actions. Interestingly, recent work involving angiotensin IV demonstrates that this peptide binds to specific receptors and may be Keywords: angiotensin metabolites; angiotensin III; angiotensin II(1-7); angiotensin IV; globin Bioactive angiotensin peptidesThe renin-angiotensin system (RAS) was initially identified as a circulating humoral system with the effector peptide, angiotensin II (Ang II), generated by an enzymatic cascade. Angiotensinogen, which is synthesized in the liver, is cleaved by renin, a product of the juxtaglomerular cells of the kidney, to form Ang I, which in turn is cleaved by angiotensinconverting enzyme (ACE) to form Ang II. ACE is membrane bound and predominates on the endothelial cells of all vascular beds. Apart from the production of Ang II in plasma, Ang II, renin and ACE have all been described in tissues such as the brain, kidney, adrenal, vasculature, heart and ovaries. This suggests a separate and distinct RAS in these tissues and implies endocrine, paracrine and autocrine roles for Ang II. Actions of Ang IIAng II regulates blood pressure, fluid volume homeostasis and pituitary hormone release via AT 1 and AT 2 receptors located in the kidney, adrenal gland, and the cardiovascular and nervous systems. [2][3][4][5] In the kidney, for instance, Ang II acts on renal vessels, glomeruli, tubules and renomedullary interstitial cells, to alter renal blood flow, glomerular filtration rate and electrolyte reabsorption.6-9 Ang II also acts on the adrenal cortex to stimulate aldosterone secretion and hence renal sodium reabsorption. 10Ang II is a potent vasoconstrictor, acting directly on vascular smooth muscle and indirectly via facilitation of noradrenaline release from sympathetic terminals. 11,12 In the heart, Ang II exerts positive iono- tropic and chronotropic effects and facilitates sympathetic activity. 13Acting on the brain, Ang II induces fluid and salt ingestion, modulates neuroendocrine systems, including vasopressin and corticotropin releasing factor release, and interacts with the autonomic control of the cardiovascular system to influence blood pressure. 3,14,15 In many instances, these effects are complementary to those of the systemic peptide on peripheral target organs. Thus, systematic Ang II affects the brain through AT 1 receptors located in the circumventricular organs, regions with a deficient blood brain barrier. In addition, endogenous neurally derived Ang II appears to act at many central nervous system sites behind the blood brain barrier. [16][17][18] Most of the classical actions of Ang II are mediated via the AT 1 receptor whereas AT 2 receptor stimulation may cause opposing effects. This was o...

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Regulatory role of brain angiotensins in the control of physiological and behavioral responses

Cited by 269 publications

References 394 publications

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

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

Salty taste acceptance by infants and young children is related to birth weight: longitudinal analysis of infants within the normal birth weight range

Bioactive angiotensin peptides

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