Cerebral Na concentration, Na appetite and thirst of sheep: influence of somatostatin and losartan

2001 ◽  
Vol 280 (3) ◽  
pp. R686-R694 ◽  
Author(s):  
R. S. Weisinger ◽  
J. R. Blair-West ◽  
P. Burns ◽  
D. A. Denton ◽  
B. Purcell
Keyword(s):  
Receptor Antagonist ◽  
Water Intake ◽  
Ang Ii ◽  
Intracerebroventricular Infusion ◽  
Effective Water

Na and water intakes of Na-depleted sheep are influenced by changes in cerebral Na concentration. The effect of intracerebroventricular infusion of somatostatin or losartan, the ANG II type 1 receptor antagonist, on the Na appetite and thirst of Na-depleted sheep during infusions that decrease (intracerebroventricular hypertonic mannitol) or increase (intracerebroventricular or systemic hypertonic NaCl) cerebral Na concentration was investigated. Na intake was increased but water intake was unchanged during intracerebroventricular infusion of hypertonic mannitol. The increased Na appetite caused by intracerebroventricular infusion of hypertonic mannitol was decreased by concurrent intracerebroventricular infusion of either somatostatin or losartan, with somatostatin being most effective. Water intake was increased during intracerebroventricular infusion of hypertonic mannitol and somatostatin. Na intake was decreased and water intake was increased during systemic or intracerebroventricular infusion of hypertonic NaCl. Intracerebroventricular infusion of losartan blocked both (Na and water intake), whereas somatostatin did not influence either of these changes in intake. The results further consolidate a role for somatostatin and ANG II in the central mechanisms controlling Na appetite and thirst of sheep.

Role of brain angiotensin II in thirst and sodium appetite of sheep

1997 ◽  
Vol 273 (1) ◽  
pp. R187-R196 ◽  
Author(s):  
R. S. Weisinger ◽  
J. R. Blair-West ◽  
D. A. Denton ◽  
E. Tarjan
Keyword(s):  
Angiotensin Ii ◽  
Receptor Antagonist ◽  
Water Intake ◽  
Neural System ◽  
At1 Receptor ◽  
Hypertonic Solution ◽  
Ang Ii ◽  
Sodium Appetite ◽  
Intracerebroventricular Infusion

The contribution of brain angiotensin II (ANG II) to thirst and Na+ appetite of sheep was evaluated. Thirst was stimulated by water deprivation, intracarotid or intracerebroventricular infusion of ANG II, or intracarotid or intracerebroventricular infusion of hypertonic solution. Intracerebroventricular infusion, over 1-3 h, of the ANG II type 1 (AT1) receptor antagonist, losartan, decreased or abolished water intake caused by all of the stimuli tested. Intracerebroventricular infusion of ZD-7155, another AT1-receptor antagonist, blocked ANG II-induced water intake. Neither losartan nor ZD-7155 infused intracerebroventricularly altered the Na+ appetite of Na(+)-depleted sheep. Intracerebroventricular infusion of losartan over 3 h, however, did block the increase in water intake and the decrease in Na+ intake caused by intracerebroventricular infusion of hypertonic NaCl in Na(+)-depleted sheep. Intracerebroventricular infusion of the ANG II type 2 (AT2) receptor antagonist, PD-123319, over 1-3 h, did not alter ANG II-induced water intake or Na+ depletion-induced Na+ intake. These results are consistent with the proposition that brain ANG II, working via AT1 receptors, is involved in the neural system controlling some aspects of physiological thirst and Na+ appetite. A role for AT2 receptors in physiological thirst or Na+ appetite is not supported by the present results.

scholarly journals Mitochondrial angiotensin II receptors regulate oxygen consumption in kidney mitochondria from healthy and type 1 diabetic rats

2020 ◽  
Vol 318 (3) ◽  
pp. F683-F688 ◽  
Author(s):  
Malou Friederich-Persson ◽  
Patrik Persson
Keyword(s):  
Nitric Oxide ◽  
Oxygen Consumption ◽  
Angiotensin Ii ◽  
Receptor Antagonist ◽  
Diabetic Rats ◽  
Kidney Cortex ◽  
Ang Ii ◽  
Kidney Mitochondria ◽  
Receptor Inhibition

Exaggerated activation of the renin-angiotensin-aldosterone system (RAAS) is a key feature in diseases such as hypertension, diabetes, and chronic kidney disease. Recently, an intracellular RAAS was demonstrated with angiotensin II (ANG II) type 1 (AT1) and type 2 (AT2) receptors expressed in nuclei and mitochondria. Diabetes is associated with both mitochondrial dysfunction and increased intracellular ANG II concentration in the kidney cortex. The present study investigated the role of ANG II signaling in kidney cortex mitochondria isolated from control and streptozotocin-induced diabetic rats. Mitochondrial oxygen consumption was evaluated after addition of ANG II alone or after preincubation with candesartan (AT1 receptor antagonist), PD-123319 (AT2 receptor antagonist), or the two in combination. ANG II binds to only mitochondrial AT2 receptors in control rats and both AT1 receptors and AT2 receptors in diabetic rats. ANG II decreased oxygen consumption in mitochondria from both control and diabetic rats. ANG II response was reversed to increased oxygen consumption by the nitric oxide synthase inhibitor N-nitro-l-arginine methyl ester. AT1 receptor inhibition did not affect the response to ANG II, whereas AT2 receptor inhibition abolished the response in mitochondria from control rats and reversed the response to increased oxygen consumption through superoxide-induced mitochondrial uncoupling in mitochondria from diabetic rats. ANG II decrease mitochondrial respiration via AT2 receptor-mediated nitric oxide release in both control and diabetic rats. AT1 receptors do not regulate mitochondria function in control rats, whereas ANG II via AT1 receptors increase mitochondria leak respiration in diabetic animals.

scholarly journals Angiotensin II enhances GABAB receptor-mediated responses and expression in nucleus tractus solitarii of rats

2009 ◽  
Vol 297 (5) ◽  
pp. H1837-H1844 ◽  
Author(s):  
Qi Zhang ◽  
Fanrong Yao ◽  
Stephen T. O'Rourke ◽  
Steven Y. Qian ◽  
Chengwen Sun
Keyword(s):  
Angiotensin Ii ◽  
Receptor Antagonist ◽  
Receptor Agonist ◽  
Gabab Receptor ◽  
Receptor Expression ◽  
Nucleus Tractus Solitarii ◽  
Neuronal Cultures ◽  
Ang Ii ◽  
Intracerebroventricular Infusion ◽  
Cgp 35348

Angiotensin II (ANG II) increases GABAB receptor expression in neuronal cultures from the nucleus tractus solitarii (NTS). In the present study, the chronic effects of ANG II on GABAB receptor expression and activity were examined in the NTS of Sprague-Dawley rats. Intracerebroventricular infusion of ANG II caused a significant elevation in blood pressure (BP) and an increase in GABAB receptor expression in the NTS. Conversely, chronic NG-nitro-l-arginine methyl ester (l-NAME) treatment also increased BP, but had no effect on GABAB receptor expression in the NTS. Next, we examined the BP response to the GABAB receptor agonist baclofen microinjected into the NTS of ANG II- or artificial cerebrospinal fluid (aCSF)-infused rats. NTS microinjection of baclofen increased BP in both groups of rats. However, the pressor response to baclofen was enhanced in ANG II-infused rats compared with aCSF-infused rats. In addition, bilateral microinjection of the GABAB receptor antagonist CGP-35348 into the NTS evoked a decrease in BP in both group of rats, and the depressor responses to CGP-35348 were enhanced in the ANG II-infused rats. In contrast, the pressor responses to the GABAA receptor agonist muscimol and the depressor responses to the GABAA receptor antagonist bicuculline were comparable between aCSF- and ANG II-infused rats. These results indicate that chronic ANG II infusion stimulates GABAB receptor expression and augments GABAB receptor-mediated responses in the NTS. This effect could contribute to the central nervous system actions of ANG II that result in dampening of baroreflexes and elevation in arterial BP.

Intracerebroventricular infusion of angiotensin II increases water and ethanol intake in rats

1999 ◽  
Vol 277 (1) ◽  
pp. R162-R172 ◽  
Author(s):  
R. S. Weisinger ◽  
J. R. Blair-West ◽  
P. Burns ◽  
D. A. Denton
Keyword(s):  
Angiotensin Ii ◽  
Direct Effect ◽  
Water Intake ◽  
Indirect Effect ◽  
Taste Preference ◽  
Ethanol Solution ◽  
Ethanol Intake ◽  
Ang Ii ◽  
Intracerebroventricular Infusion ◽  
Stimulation Of

The influence of prolonged ingestion of ethanol on stimulation of water or ethanol intake by intracerebroventricular infusion of ANG II was evaluated in rats. Animals were maintained for 5–6 mo with either 10% ethanol solution or water as their only source of fluid. In both groups of rats, infusion of ANG II caused a large increase in water intake (7-fold) and a lesser increase in 10% ethanol intake (2-fold). The effect of ANG II on the volume of ethanol solution ingested, however, was inversely related to the concentration of the ethanol solution. As the concentration of ethanol solution was decreased, frequency and duration of drinking bouts increased. The intake of sweetened 10% ethanol solution or commercially produced wine during infusion of ANG II was similar to the intake of 10% ethanol and not related to taste preference. In conclusion, chronic consumption of ethanol solution did not appear to adversely effect ANG II stimulation of water intake. The intake of ethanol solution during infusion of ANG II was inhibited by a direct effect of ingested ethanol and/or by indirect effect from metabolized ethanol.

Intracerebroventricular losartan inhibits postprandial drinking in sheep

1997 ◽  
Vol 272 (4) ◽  
pp. R1055-R1059 ◽  
Author(s):  
M. Mathai ◽  
M. D. Evered ◽  
M. J. McKinley
Keyword(s):  
Cerebrospinal Fluid ◽  
Angiotensin Ii ◽  
Food Intake ◽  
Water Intake ◽  
Fluid Balance ◽  
Intravenous Infusion ◽  
Ang Ii ◽  
Intracerebroventricular Infusion ◽  
Drinking Response ◽  
Dependent Mechanism

We investigated the contribution of brain angiotensinergic mechanisms to postprandial drinking in sheep. Sheep in fluid balance were given 0.8 kg chaff for 30 min, and water intake was measured for the next hour. Intracerebroventricular infusion of the AT1 type angiotensin II (ANG II) receptor blocker losartan (1 mg/h) reduced postprandial drinking by approximately 70% (n = 7, P < 0.01) but did not affect food intake. The same losartan dose given intravenously had little or no effect on prandial drinking. Feeding increased Na+ concentrations in plasma and cerebrospinal fluid (CSF; n = 5, P < 0.05). Intracerebroventricular losartan (1 mg/h) inhibited the drinking responses to intracarotid infusion of ANG II (0.8 microg/min for 30 min, n = 4, P < 0.01) and to intracerebroventricular infusion of 0.5 M NaCl (1 ml/h for 1 h, n = 5, P < 0.05) but had no effect on drinking responses to intravenous infusion of 4 M NaCl (1.3 ml/min for 30 min). These findings indicate that a brain ANG II-dependent mechanism is involved in postprandial drinking in sheep. They suggest also that the mechanism by which increasing CSF Na+ causes thirst involves brain ANG II and is different from the mechanism subserving the drinking response to changes in blood Na+.

Central infusion of aliskiren prevents sympathetic hyperactivity and hypertension in Dahl salt-sensitive rats on high salt intake

2012 ◽  
Vol 302 (7) ◽  
pp. R825-R832 ◽  
Author(s):  
Bing S. Huang ◽  
Roselyn A. White ◽  
Li Bi ◽  
Frans H. H. Leenen
Keyword(s):  
Salt Intake ◽  
High Salt ◽  
Receptor Blocker ◽  
Ang Ii ◽  
Sympathetic Hyperactivity ◽  
Direct Renin Inhibitor ◽  
Intracerebroventricular Infusion ◽  
High Salt Intake ◽  
The Brain

Central infusion of an angiotensin type 1 (AT1) receptor blocker prevents sympathetic hyperactivity and hypertension in Dahl salt-sensitive (S) rats on high salt. In the present study, we examined whether central infusion of a direct renin inhibitor exerts similar effects. Intracerebroventricular infusion of aliskiren at the rate of 0.05 mg/day markedly inhibited the increase in ANG II levels in the cerebrospinal fluid and in blood pressure (BP) caused by intracerebroventricular infusion of rat renin. In Dahl S rats on high salt, intracerebroventricular infusion of aliskiren at 0.05 and 0.25 mg/day for 2 wk similarly decreased resting BP in Dahl S rats on high salt. In other groups of Dahl S rats, high salt intake for 2 wk increased resting BP by ∼25 mmHg, enhanced pressor and sympathoexcitatory responses to air-stress, and desensitized arterial baroreflex function. All of these effects were largely prevented by intracerebroventricular infusion of aliskiren at 0.05 mg/day. Aliskiren had no effects in rats on regular salt. Neither high salt nor aliskiren affected hypothalamic ANG II content. These results indicate that intracerebroventricular infusions of aliskiren and an AT1 receptor blocker are similarly effective in preventing salt-induced sympathetic hyperactivity and hypertension in Dahl S rats, suggesting that renin in the brain plays an essential role in the salt-induced hypertension. The absence of an obvious increase in hypothalamic ANG II by high salt, or decrease in ANG II by aliskiren, suggests that tissue levels do not reflect renin-dependent ANG II production in sympathoexcitatory angiotensinergic neurons.

scholarly journals mTORC1 Signaling Contributes to Drinking But Not Blood Pressure Responses to Brain Angiotensin II

Endocrinology ◽  
2016 ◽  
Vol 157 (8) ◽  
pp. 3140-3148 ◽  
Author(s):  
Kenjiro Muta ◽  
Donald A. Morgan ◽  
Justin L. Grobe ◽  
Curt D. Sigmund ◽  
Kamal Rahmouni
Keyword(s):  
Angiotensin Ii ◽  
Water Intake ◽  
Drinking Behavior ◽  
Subfornical Organ ◽  
Dependent Manner ◽  
Ang Ii ◽  
Mtorc1 Signaling ◽  
Wide Range ◽  
The Brain

Mechanistic target of rapamycin complex 1 (mTORC1) is a molecular node that couples extracellular cues to a wide range of cellular events controlling various physiological processes. Here, we identified mTORC1 signaling as a critical mediator of angiotensin II (Ang II) action in the brain. In neuronal GT1–7 cells, we show that Ang II stimulates neuronal mTORC1 signaling in an Ang II type 1 receptor-dependent manner. In mice, a single intracerebroventricular (ICV) injection or chronic sc infusion of Ang II activated mTORC1 signaling in the subfornical organ, a critical brain region in cardiovascular control and fluid balance. Moreover, transgenic sRA mice with brain-specific overproduction of Ang II displayed increased mTORC1 signaling in the subfornical organ. To test the functional role of brain mTORC1 in mediating the action of Ang II, we examined the consequence of mTORC1 inhibition with rapamycin on Ang II-induced increase in water intake and arterial pressure. ICV pretreatment with rapamycin blocked ICV Ang II-mediated increases in the frequency, duration, and amount of water intake but did not interfere with the pressor response evoked by Ang II. In addition, ICV delivery of rapamycin significantly reduced polydipsia, but not hypertension, of sRA mice. These results demonstrate that mTORC1 is a novel downstream pathway of Ang II type 1 receptor signaling in the brain and selectively mediates the effect of Ang II on drinking behavior.

Role of angiotensin-converting enzyme and angiotensin II in development of hypoxic pulmonary hypertension

1995 ◽  
Vol 269 (4) ◽  
pp. H1186-H1194 ◽  
Author(s):  
N. W. Morrell ◽  
K. G. Morris ◽  
K. R. Stenmark
Keyword(s):  
Pulmonary Hypertension ◽  
Angiotensin Ii ◽  
Receptor Antagonist ◽  
Vascular Remodeling ◽  
Ace Inhibition ◽  
Protective Effects ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Hypoxic Pulmonary Hypertension

Although angiotensin converting enzyme (ACE) inhibitors are known to attenuate the development of hypoxic pulmonary hypertension in rats, the precise mechanism of this protective effect remains unknown. Thus we utilized specific angiotensin II (ANG II)-receptor antagonists to investigate whether ANG II is involved directly in the hemodynamic and structural changes of pulmonary hypertension, and we tested whether the protective effects of ACE inhibition can be attributed partly to potentiation of bradykinin. During 14 days of hypobaric hypoxia, rats received, via intraperitoneal osmotic minipumps, either 1) the ACE inhibitor captopril, 2) captopril plus the bradykinin B2-receptor antagonist CP-0597, 3) the ANG II type 1 receptor antagonist losartan, 4) the ANG II type 2 receptor antagonist PD-123319, or 5) saline. At 14 days, mean pulmonary arterial pressure (MPAP) was reduced (P < 0.05) in hypoxic rats treated with captopril (26.6 +/- 0.8 mmHg) or losartan (24.4 +/- 1.0 mmHg) compared with saline (32.0 +/- 1.4 mmHg) but was unaffected by PD-123319 (29.5 +/- 1.7 mmHg). Right ventricular hypertrophy was reduced in hypoxic rats treated with captopril or losartan compared with saline-treated rats. Morphometry showed less medial thickening and peripheral muscularization of small pulmonary arteries in hypoxic animals treated with captopril or losartan. Coadministration of CP-0597 did not reverse the protective effects of captopril on pulmonary vascular remodeling. These results suggest a novel role for endogenous ANG II, acting through the type 1 receptor, in the vascular remodeling associated with hypoxic pulmonary hypertension. The beneficial effects of ACE inhibition in this model can be attributed to reduced ANG II production rather than potentiation of bradykinin.

Mode of action of ANG II on ion transport in guinea pig distal colon

2000 ◽  
Vol 278 (4) ◽  
pp. G625-G634 ◽  
Author(s):  
Yutaka Hosoda ◽  
Adi Winarto ◽  
Toshihiko Iwanaga ◽  
Atsukazu Kuwahara
Keyword(s):  
Epithelial Cells ◽  
Guinea Pig ◽  
Ion Transport ◽  
Receptor Antagonist ◽  
Distal Colon ◽  
Evoked Response ◽  
Maximal Response ◽  
Prostaglandin E ◽  
Ang Ii

The effect of ANG II on mucosal ion transport and localization of ANG type 1 receptor (AT1R) in the guinea pig distal colon was investigated. Submucosal/mucosal segments were mounted in Ussing flux chambers, and short-circuit current ( I sc) was measured as an index of ion transport. Serosal addition of ANG II produced a concentration-dependent (10− 9–10− 5M) increase in I sc. The maximal response was observed at 10− 6 M; the increase in I sc was 164.4 ± 11.8 μA/cm2. The ANG II (10− 6 M)-evoked response was mainly due to Cl− secretion. Tetrodotoxin, atropine, the neurokinin type 1 receptor antagonist FK-888, and piroxicam significantly reduced the ANG II (10− 6M)-evoked response to 28, 45, 58, and 16% of control, respectively. Pretreatment with prostaglandin E2(10− 5 M) resulted in a threefold increase in the ANG II-evoked response. The AT1R antagonist FR-130739 completely blocked ANG II (10− 6M)-evoked responses, whereas the ANG type 2 receptor antagonist PD-123319 had no effect. Localization of AT1R was determined by immunohistochemistry. In the immunohistochemical study, AT1R-immunopositive cells were distributed clearly in enteric nerves and moderately in surface epithelial cells. These results suggest that ANG II-evoked electrogenic Cl−secretion may involve submucosal cholinergic and tachykinergic neurons and prostanoid synthesis pathways through AT1R on the submucosal plexus and surface epithelial cells in guinea pig distal colon.

Functional evidence for alternative ANG II-forming pathways in hamster cardiovascular system

1998 ◽  
Vol 275 (4) ◽  
pp. H1307-H1312 ◽  
Author(s):  
Hikaru Nishimura ◽  
Hendrik Buikema ◽  
Ovidiu Baltatu ◽  
Detlev Ganten ◽  
Hidenori Urata
Keyword(s):  
Receptor Antagonist ◽  
Cardiovascular System ◽  
Trypsin Inhibitor ◽  
Alternative Pathway ◽  
Ang Ii ◽  
Similar Dose ◽  
Pressor Responses ◽  
Isolated Aorta ◽  
Dose Dependent

Like human chymase, hamster chymase is an ANG II-forming enzyme, but pathophysiological roles of chymase are still unknown. We determined the functional conversion of ANG I and [Pro11, d-Ala12]ANG I, a chymase-selective substrate, to ANG II in the hamster cardiovascular system. ANG I and [Pro11, d-Ala12]ANG I produced similar dose-dependent pressor responses in conscious hamsters. Captopril and CV-11974, an ANG II type 1 (AT1)-receptor antagonist, inhibited the responses to ANG I; in contrast, the pressor responses to [Pro11,d-Ala12]ANG I were suppressed only by CV-11974. In the isolated aorta, captopril suppressed ANG I-induced contraction by 84%; administration of captopril with either chymostatin or aprotinin eliminated the contraction. [Pro11, d-Ala12]ANG I-induced contraction was not affected by captopril but was attenuated by chymostatin (71%) and aprotinin (57%). CV-11974 abolished the responses to both substrates, whereas PD-123319, an AT2-receptor antagonist, had no effect. In homogenates of the aorta and heart, soybean trypsin inhibitor-inhibitable ANG II formation predominated over captopril- or aprotinin-inhibitable ANG II formation. These data suggest that [Pro11,d-Ala12]ANG I and part of ANG I were functionally converted to ANG II by chymase and other serine protease(s) in hamster vessels, inducing AT1-receptor-mediated vasoconstriction. Biochemical data supported a role for chymase in the alternative pathway.

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