Role of Angiotensin Ii and the Subfornical Organ in the Pharmacological Actions of Ethanol

Grobe, Justin L; Rowland, Neil E.; Katovich, Michael J.

doi:10.1093/alcalc/agh079

Cited by 6 publications

(7 citation statements)

References 48 publications

(76 reference statements)

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“…20 Interestingly, lesion studies suggest that the SFO may mediate some thermogenic effects of Ang-II in rats. 34 Moreover, sRA double transgenic mice which exhibit abundant Ang-II in the SFO exhibit increased metabolic rate. 5 It was therefore surprising that SFO-targeted deletion of the AT 1a R did not attenuate the induction of resting metabolism by DOCA-salt.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin Type 1a Receptors in the Subfornical Organ Are Required for Deoxycorticosterone Acetate-Salt Hypertension

et al. 2013

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Although elevated renin-angiotensin system activity and angiotensinergic signaling within the brain are required for hypertension, polydipsia and increased metabolic rate induced by deoxycorticosterone acetate (DOCA)-salt, the contribution of specific receptor subtypes and brain nuclei mediating these responses remains poorly defined. We hypothesized that angiotensin type 1a receptors (AT1aR) within the subfornical organ (SFO) mediate these responses. Transgenic mice carrying a conditional allele of the endogenous AT1aR (AT1aRflox) were administered an adenovirus encoding Cre-recombinase and eGFP (AdCRE) or eGFP alone (AdGFP) into the lateral cerebral ventricle. AdCRE reduced AT1aR mRNA and induced recombination in AT1aRflox genomic DNA specifically in the SFO, without significant effect in the paraventricular or arcuate nuclei, and also induced SFO-specific recombination in ROSATdTomato reporter mice. The effect of SFO-targeted ablation of endogenous AT1aR was evaluated in AT1aRflox mice at three time points: 1) baseline, 2) one week after virus injection but before DOCA-salt, and 3) after three weeks of DOCA-salt. DOCA-salt treated mice with deletion of AT1aR in SFO exhibited a blunted increase in arterial pressure. Increased sympathetic cardiac modulation and urine copeptin, a marker of vasopressin release, were both significantly reduced in DOCA-salt mice when AT1aR was deleted in the SFO. Additionally, deletion of AT1aR in the SFO significantly attenuated the polydipsia, polyuria and sodium intake in response to DOCA-salt. Together, these data highlight the contribution of AT1aR in the SFO to arterial pressure regulation potentially through changes on sympathetic cardiac modulation, vasopressin release and hydromineral balance in the DOCA-salt model of hypertension.

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Section: Discussionmentioning

confidence: 99%

Angiotensin Type 1a Receptors in the Subfornical Organ Are Required for Deoxycorticosterone Acetate-Salt Hypertension

et al. 2013

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“…However, hypothalamic regions expressing ANG II, such as the POA and paraventricular nucleus, are possible sites at which ANG II may influence thermoregulation during exercise (14). Therefore, we hypothesized that infusion of Los into the cerebral ventricle would perfuse to the SFO and other thermoregulatory centers situated in the hypothalamus, inhibiting the heat loss response and accelerating the BHR and HSR during prolonged exercise.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, it has recently been shown that inhibition of the POA/AH by local infusion of tetrodotoxin impairs heat loss in running rats (16). A variety of studies have suggested that SFO and other adjacent areas are critical for the central actions of ANG II (7,14) and that SFO afferent communication with paraventricular nucleus utilizes ANG II as a neurotransmitter within this hypothalamic region (25). Moreover, lesion of the SFO resulted in abolished ANG II-mediated temperature response (7).…”

Section: Discussionmentioning

confidence: 99%

“…These receptors are widely spread through the central nervous system (CNS), including the preoptic area/ anterior hypothalamus (POA/AH), regions of the hypothalamus considered to be the integrative centers of body temperature (5,29,34,35). In addition, the subfornical organ (SFO) is critical for the central actions of ANG II (8,14). The AT 1 -receptor antagonist losartan (Los) has been used to investigate the role of ANG II in T b .…”

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confidence: 99%

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Central angiotensin AT₁-receptor blockade affects thermoregulation and running performance in rats

Leite

Lacerda²,

Marubayashi³

et al. 2006

American Journal of Physiology-Regulatory, Integrative and Comp

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The effect of central angiotensin AT 1-receptor blockade on thermoregulation in rats during exercise on a treadmill (18 m/min, 5% inclination) was investigated. Core (T b) and skin tail temperatures were measured in rats while they were exercising until fatigue after injection of 2 l of losartan (Los; 20 nmol, n ϭ 4; 30 nmol, n ϭ 4; 60 nmol, n ϭ 7), an angiotensin II AT 1-receptor antagonist, or 2 l of 0.15 mol/l NaCl (Sal; n ϭ 15) into the right lateral cerebral ventricle. Body heat rate (BHR), heat storage rate, threshold Tb for tail vasodilation (TTbV), time to fatigue, and workload were calculated. During exercise, the BHR and heat storage rate of Los-treated animals were, respectively, 40 and 53% higher (P Ͻ 0.01) than in Sal-treated animals. Additionally, rats injected with Los showed an increased TTbV (38.59 Ϯ 0.19°C for Los vs. 38.12 Ϯ 0.1°C for Sal, P Ͻ 0.02), a higher Tb at fatigue point (39.07 Ϯ 0.14°C Los vs. 38.66 Ϯ 0.07°C Sal, P Ͻ 0.01), and a reduced running performance (27.29 Ϯ 4.48 min Los vs. 52.47 Ϯ 6.67 min Sal, P Ͻ 0.01), which was closely related to the increased BHR. Our data suggest that AT1-receptor blockade attenuates heat dissipation during exercise due to the higher TTbV, leading to a faster exercise-induced increase in Tb, thus decreasing running performance. tail vasodilation; fatigue; heat balance ACTING CENTRALLY, ANGIOTENSIN II (ANG II), exerts thermoregulatory effects characterized by a decreased metabolic rate, a fall in core temperature (T b ), and an increase in tail skin temperature (T tail ) (43,44,46), through angiotensin type 1 (AT 1 ) receptors. These receptors are widely spread through the central nervous system (CNS), including the preoptic area/ anterior hypothalamus (POA/AH), regions of the hypothalamus considered to be the integrative centers of body temperature (5,29,34,35). In addition, the subfornical organ (SFO) is critical for the central actions of ANG II (8, 14). The AT 1 -receptor antagonist losartan (Los) has been used to investigate the role of ANG II in T b . Some studies have observed that intracerebroventricular (icv) injection of Los inhibited the hypothermic effect of ANG II, producing an increase in T b of resting animals exposed to a hot environment (7,27). In addition, Horowitz and colleagues (17,36) showed that central administration of Los elevates the temperature threshold for peripheral vasodilation and causes a downward shift in the threshold for evaporative cooling during heat stress, indicating the involvement of hypothalamic angiotensinergic signaling in thermoregulation. Because hypothermia and increased heat dissipation may be neuroprotective, activation of central angiotensinergic transmission may exert important effects on thermoregulation during exercise, influencing running performance.Elevated internal body temperature and increased heat storage (9, 12, 30) have been considered to be limiting factors that reduce the CNS drive for exercise performance (31,32,40) and precipitate feelings of fatigue, thus protecting the brain from ther...

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“…This conclusion is supported by the finding that enalapril did not alter esophageal or mean skin temperature in humans during exercise in the heat (Mittleman, 1996) and that peripherally administered losartan had no effect on temperature regulation in control rats during heat stress (Horowitz et al, 1999). However, peripherally administered losartan did prevent the decrease in colonic temperature that follows administration of ethanol (Grobe et al, 2004) and did affect the later colonic temperature response to isoproterenol (Fregly and Rowland, 1993). Furthermore, the colonic temperature threshold for salivation in heat acclimated rats was increased by peripheral administration of losartan (Horowitz et al, 1999).…”

Section: Discussionmentioning

confidence: 79%

Endogenous angiotensin II and the regulation of oxygen consumption and colonic temperature in rats

Barney

Greenheck

Nehs

et al. 2012

Journal of Thermal Biology

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Role of Angiotensin Ii and the Subfornical Organ in the Pharmacological Actions of Ethanol

Cited by 6 publications

References 48 publications

Angiotensin Type 1a Receptors in the Subfornical Organ Are Required for Deoxycorticosterone Acetate-Salt Hypertension

Angiotensin Type 1a Receptors in the Subfornical Organ Are Required for Deoxycorticosterone Acetate-Salt Hypertension

Central angiotensin AT₁-receptor blockade affects thermoregulation and running performance in rats

Endogenous angiotensin II and the regulation of oxygen consumption and colonic temperature in rats

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Role of Angiotensin Ii and the Subfornical Organ in the Pharmacological Actions of Ethanol

Cited by 6 publications

References 48 publications

Angiotensin Type 1a Receptors in the Subfornical Organ Are Required for Deoxycorticosterone Acetate-Salt Hypertension

Angiotensin Type 1a Receptors in the Subfornical Organ Are Required for Deoxycorticosterone Acetate-Salt Hypertension

Central angiotensin AT1-receptor blockade affects thermoregulation and running performance in rats

Endogenous angiotensin II and the regulation of oxygen consumption and colonic temperature in rats

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Central angiotensin AT₁-receptor blockade affects thermoregulation and running performance in rats