Central ANG II-receptor antagonists impair cardiovascular and vasopressin response to hemorrhage in rats

Lee, Won-Jae; Yang, Eun-Kyoung; Ahn, Dongbin; Park, Y. Y.; Park, J.S.; Kim, H. J.

doi:10.1152/ajpregu.1995.268.6.r1500

Cited by 21 publications

(21 citation statements)

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“…Systemic stimuli that may activate central angiotensinergic pathways include plasma hypertonicity and circulating hormones such as angiotensin II or relaxin. There is also evidence that brain angiotensinergic pathways have a role in regulating arterial pressure [83][84][85]. Several gaps in our knowledge of these angiotensinergic pathways still exist and await further elucidation.…”

Section: Resultsmentioning

confidence: 99%

Brain Angiotensin and Body Fluid Homeostasis.

McKinley

Allen²,

Mathai³

et al. 2001

JJP

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The circulating hormone angiotensin II is an important humoral factor regulating cardiovascular and body fluid and electrolyte homeostasis. Potent direct constrictor actions on the vasculature, stimulation of the sodium-retaining hormone aldosterone from the adrenal cortex, generation of thirst and sodium appetite, release of the urine-concentrating hormone vasopressin, intrarenal regulation of tubular-glomular balance, and feedback inhibition of renal renin release are just some of the well recognized actions of this circulating octapeptide. But angiotensin II may have further roles in regulating body fluid homeostasisnot as a blood-borne hormone, but as a neuropeptide generated within the central nervous system (CNS), where it may act as a neurotransmitter or modulator of neural function to influence thirst, vasopressin secretion, renin release, sodium excretion, and body temperature. Localization of an Angiotensinergic System in the Brain and Spinal Cord AngiotensinogenDuring the past 25 years, much evidence has emerged that supports the view that angiotensin II and its active metabolites are generated in the brain from centrally synthesized angiotensinogen. The principle Key words: angiotensin, AT 1 receptors, sodium, osmoregulation, thermoregulation.Abstract: Angiotensinogen, the precursor molecule of the peptides angiotensin I, II, and III, is synthesized in the brain and the liver. Evidence is reviewed that angiotensin II, and possibly angiotensin III, that are generated within the brain act within neural circuits of the central nervous system to regulate body fluid balance. Immunohistochemical studies in the rat brain have provided evidence of angiotensin-containing neurons, especially in the hypothalamic paraventricular nucleus, subfornical organ, periventricular region, and nucleus of the solitary tract, as well as in extensive angiotensin-containing fiber pathways. Angiotensin immunoreactivity is observed by electron microscope in synaptic vesicles in several brain regions, the most prominent of these being the central nucleus of the amygdala. Neurons in many parts of the brain (lamina terminalis, paraventricular and parabrachial nuclei, ventrolateral medulla, and nucleus of the solitary tract) known to be involved in the regulation of body fluid homeostasis exhibit angiotensin receptors of the AT 1 subtype. Pharmacological studies in several species show that intracerebroventricular administration of AT 1 receptor antagonist drugs inhibit homeostatic responses to the central administration of hypertonic saline, intravenous infusion of the hormone relaxin, or thermal dehydration. Responses affected by centrally administered AT 1 antagonists are water drinking, vasopressin secretion, natriuresis, increased arterial pressure, reduced renal renin release, salt hunger, and thermoregulatory adjustments. We conclude that angiotensinergic neural pathways in the brain probably have an important homeostatic function, especially in regard to osmoregulation and thermoregulation, and the maintenance of arterial p...

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Section: Resultsmentioning

confidence: 99%

Brain Angiotensin and Body Fluid Homeostasis.

McKinley

Allen²,

Mathai³

et al. 2001

JJP

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“…However, it seems likely that peripheral effects dominate, since the peptide angiotensin receptor antagonist saralasin, which is unlikely to cross the blood brain barrier, augmented the depressor response to hemorrhage when given intravenously (Spielman et al, 1975). Nevertheless, the effects of AT 1 -receptor blockade may be partly mediated within the central nervous system, since Lee et al (1995) demonstrated that intracerebroventricular administration of low doses of losartan or saralasin can blunt compensatory responses to hemorrhage, while Mathai et al (1997) found that intracerebroventricular losartan reduced the level of blood loss required to elicit the decompensatory phase of the response to hemorrhage (Evans et al, 2001). A second limitation of our study was that we did not obtain any measures of the activity of the SNS, so interpretation of our findings with respect to autonomic control of the circulation must be associated with caution.…”

Section: Discussionmentioning

confidence: 99%

“…It also blunted the recovery of MAP after hemorrhage in conscious rats, without altering the acute response of MAP to blood loss (Ponchon and Elghozi, 1997). Other studies have demonstrated an augmented depressor response to hemorrhage after blockade of central AT 1 -receptors in conscious rats (Lee et al, 1995) or systemic AT 1 -receptor blockade in conscious dogs (Francis et al, 2004), or an early occurrence of the decompensatory phase of the response to progressive hypovolemia in conscious sheep after central AT 1 -receptor blockade (Mathai et al, 1997). Yet in only one of these studies was cardiac output (CO) measured (Francis et al, 2004) and in none was renal blood flow (RBF) measured.…”

Section: Introductionmentioning

confidence: 96%

Angiotensin II Type 1 Receptors and Systemic Hemodynamic and Renal Responses to Stress and Altered Blood Volume in Conscious Rabbits

Xu¹,

Eppel²,

Head³

et al. 2011

Front. Physio.

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We examined how systemic blockade of type 1 angiotensin (AT1-) receptors affects reflex control of the circulation and the kidney. In conscious rabbits, the effects of candesartan on responses of systemic and renal hemodynamics and renal excretory function to acute hypoxia, mild hemorrhage, and plasma volume expansion were tested. Candesartan reduced resting mean arterial pressure (MAP, −8 ± 2%) without significantly altering cardiac output (CO), increased renal blood flow (RBF, +38 ± 9%) and reduced renal vascular resistance (RVR, −32 ± 6%). Glomerular filtration rate (GFR) was not significantly altered but sodium excretion (UNa+V) increased fourfold. After vehicle treatment, hypoxia (10% inspired O2 for 30 min) did not significantly alter MAP or CO, but reduced heart rate (HR, −17 ± 6%), increased RVR (+33 ± 16%) and reduced GFR (−46 ± 16%) and UNa+V (−41 ± 17%). Candesartan did not significantly alter these responses. After vehicle treatment, plasma volume expansion increased CO (+35 ± 7%), reduced total peripheral resistance (TPR, −26 ± 5%), increased RBF (+62 ± 23%) and reduced RVR (−32 ± 9%), but did not significantly alter MAP or HR. It also increased UNa+V (803 ± 184%) yet reduced GFR (−47 ± 9%). Candesartan did not significantly alter these responses. After vehicle treatment, mild hemorrhage did not significantly alter MAP but increased HR (+16 ± 3%), reduced CO (−16 ± 4%) and RBF (−18 ± 6%), increased TPR (+18 ± 4%) and tended to increase RVR (+18 ± 9%, P = 0.1), but had little effect on GFR or UNa+V. But after candesartan treatment MAP fell during hemorrhage (−19 ± 1%), while neither TPR nor RVR increased, and GFR (−64 ± 18%) and UNa+V (−83 ± 10%) fell. AT1-receptor activation supports MAP and GFR during hypovolemia. But AT1-receptors appear to play little role in the renal vasoconstriction, hypofiltration, and antinatriuresis accompanying hypoxia, or the systemic and renal vasodilatation and natriuresis accompanying plasma volume expansion.

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“…Interestingly, acute i.c.v. administration of losartan and saralasin reduced tachycardia and produced a greater fall in blood pressure during hemorrhage in SHR and Wistar, but not WKY rats [59], indicating that the functional importance of brain Ang II in the sympathoexcitatory response to hemorrhage may vary even between strains of rats. It also appears that central AT 1 receptor-dependent excitatory pathways are not critical in the sympathetic response to hypoxia in rabbits [41].…”

Section: Influence Of Brain Ang II On Autonomic Response To Stressmentioning

confidence: 93%

Brain Angiotensin and Cardiovascular Reactivity to Negative and Positive Emotional Stress

Mayorov

2007

CHYR

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Cardiovascular reactivity, an abrupt increase in blood pressure and heart rate in response to negative emotional stress is a risk factor for hypertension and heart disease. Brain angiotensin II (Ang II) has been recognized as an important regulator of cardiovascular reactivity. Apart from threatening events, exposure to appetitive stimuli is capable of inducing a distinct, sympathetically mediated rise in blood pressure in both animals and humans. Recent animal studies employing microinjection of AT 1 receptor antagonists directly into hypothalamic and brainstem nuclei indicate that locally released AngII acts to facilitate, through a superoxide-dependent mechanism, the pressor response to negative stress. Conversely, animal studies demonstrated that brain Ang II is less important in the regulation of cardiovascular arousal associated with positively motivated behavior, such as anticipation and consumption of palatable food. Thus, endogenous AngII in the brain appears to control the activation of central pathways primarily associated with the defense response, rather than nonspecifically modulating cardiovascular reactivity regardless of emotional valence (attraction or aversion) of stimuli. These findings may be of clinical importance as they suggest that targeted inhibition of Ang II -superoxide signaling in the brain may selectively reduce blood pressure reactivity to negative emotional stress, without affecting cardiovascular arousal associated with normal daily activities.

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Central ANG II-receptor antagonists impair cardiovascular and vasopressin response to hemorrhage in rats

Cited by 21 publications

References 0 publications

Brain Angiotensin and Body Fluid Homeostasis.

Brain Angiotensin and Body Fluid Homeostasis.

Angiotensin II Type 1 Receptors and Systemic Hemodynamic and Renal Responses to Stress and Altered Blood Volume in Conscious Rabbits

Brain Angiotensin and Cardiovascular Reactivity to Negative and Positive Emotional Stress

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