Role of thromboxane receptors in the dipsogenic response to central angiotensin II

2002 ◽  
Vol 282 (3) ◽  
pp. R865-R869 ◽  
Author(s):  
Chagriya Kitiyakara ◽  
William J. Welch ◽  
Joseph G. Verbalis ◽  
Christopher S. Wilcox
Keyword(s):  
Angiotensin Ii ◽  
Water Intake ◽  
Ang Ii ◽  
Tp Receptor ◽  
Drinking Response ◽  
Tp Receptors ◽  
Thromboxane Receptors ◽  
Prostaglandin H ◽  
The Brain

Central angiotensin II (ANG II) regulates thirst. Because thromboxane A2-prostaglandin H2 (TP) receptors are expressed in the brain and mediate some of the effects of ANG II in the vasculature, we investigated the hypothesis that TP receptors mediate the drinking response to intracerebroventricular (icv) injections of ANG II. Pretreatment with the specific TP-receptor antagonist ifetroban (Ifet) decreased water intake with 50 ng/kg icv ANG II (ANG II + Veh, 7.2 ± 0.7 ml vs. ANG II + Ifet, 2.8 ± 0.8 ml; n = 5 rats; P < 0.001) but had no effect on water intake induced by hypertonic saline (NaCl + Veh, 8.4 ± 1.1 ml vs. NaCl + Ifet, 8.9 ± 1.8 ml; n = 5 rats; P = not significant). Administration of 0.6 μg/kg icv of the TP-receptor agonist U-46,619 did not induce drinking when given alone but did increase the dipsogenic response to a near-threshold dose of 15 ng/kg icv ANG II (ANG II + Veh, 1.1 ± 0.7 vs. ANG II + U-46,619, 4.5 ± 0.9 ml; n = 5 rats; P < 0.01). We conclude that central TP receptors contribute to the dipsogenic response to ANG II.

Role of arteria baroreceptor input on thirst and urinary responses to intracerebroventricular angiotensin II

1993 ◽  
Vol 265 (3) ◽  
pp. R591-R595 ◽  
Author(s):  
R. L. Thunhorst ◽  
S. J. Lewis ◽  
A. K. Johnson
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Arterial Blood Pressure ◽  
Water Intake ◽  
Enzyme Inhibitor ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Arterial Blood ◽  
Endogenous Formation

Intracerebroventricular (icv) infusion of angiotensin II (ANG II) in rats elicits greater water intake under hypotensive, compared with normotensive, conditions. The present experiments used sinoaortic baroreceptor-denervated (SAD) rats and sham-operated rats to examine if the modulatory effects of arterial blood pressure on water intake in response to icv ANG II are mediated by arterial baroreceptors. Mean arterial blood pressure (MAP) was raised or lowered by intravenous (i.v.) infusions of phenylephrine (1 or 10 micrograms.kg-1 x min-1) or minoxidil (25 micrograms.kg-1 x min-1), respectively. The angiotensin-converting enzyme inhibitor captopril (0.33 mg/min) was infused i.v. to prevent the endogenous formation of ANG II during testing. Urinary excretion of water and solutes was measured throughout. Water intake elicited by icv ANG II was inversely related to changes in MAP. Specifically, rats drank more water in response to icv ANG II when MAP was reduced by minoxidil but drank less water when MAP was elevated by phenylephrine. The influence of changing MAP on the icv ANG II-induced drinking responses was not affected by SAD. These results suggest that the modulatory effects of arterial blood pressure on icv ANG II-induced drinking can occur in the absence of sinoaortic baroreceptor input.

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+.

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 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.

Extrarenal aspects of angiotensin II function

1997 ◽  
Vol 136 (4) ◽  
pp. 349-358 ◽  
Author(s):  
Tamás Csikós ◽  
Stefan Gallinat ◽  
Thomas Unger
Keyword(s):  
Cell Proliferation ◽  
Angiotensin Ii ◽  
Receptor Activation ◽  
Physiological Effect ◽  
Endothelial Cell Proliferation ◽  
Ang Ii ◽  
Receptor Ligands ◽  
Drinking Response ◽  
Receptor Inactivation

Abstract The cloning of angiotensin II (Ang II) receptor genes and the availability of specific receptor ligands allows characterization of Ang II receptor-mediated actions. Most of the well-known Ang II effects such as vasoconstriction, drinking response and cell proliferation are mediated through the AT1 receptor. Little is known about the physiological effect of the AT2 receptor, though there are some reports describing the involvement of the AT2 receptor in blood pressure regulation. Recent data demonstrate that the AT2-mediated actions are inhibitory to AT1- and mitogen-induced growth effects, indicating a balancing mechanism for Ang II-controlled mechanisms. It has also been demonstrated that AT2 receptor inactivation induces endothelial cell proliferation in the presence of Ang II. Additionally, AT2 receptor activation enhances nerve growth factor-induced differentiation of PC12W cells and a role in apoptotic changes has also been reported. Based on recent findings, this article focuses on the role of Ang II in growth and differentiation processes with respect to the AT2 receptor in these events. European Journal of Endocrinology 136 349–358

Effect of arterial pressure on drinking and urinary responses to angiotensin II

1988 ◽  
Vol 254 (1) ◽  
pp. R69-R74 ◽  
Author(s):  
M. D. Evered ◽  
M. M. Robinson ◽  
P. A. Rose
Keyword(s):  
Angiotensin Ii ◽  
Arterial Pressure ◽  
Water Intake ◽  
Fluid Loss ◽  
High Dose ◽  
Ang Ii ◽  
Intravenous Injections ◽  
Drinking Response ◽  
High Doses ◽  
The Relationship

To investigate the relationship between angiotensin II (ANG II) and mean arterial pressure (MAP) in the control of drinking in rats, we infused ANG II intravenously at constant rates (either 50 or 100 ng.kg-1.min-1 for 90 min) and varied MAP by intravenous injections of diazoxide (5-20 mg/kg). Rats were pretreated with captopril to block the endogenous synthesis of ANG II. When given alone, low and high doses of ANG II increased MAP approximately 30 and 50 mmHg, respectively. The low but not the high dose significantly increased water intake above control levels. Both doses caused such a large diuresis and natriuresis that the net effect was fluid loss. Reducing MAP toward normal greatly increased the drinking response to the high but not the low dose of ANG II and reduced the urinary solute and water loss to both doses. These results support the hypothesis that water intake and net fluid gain are inhibited when MAP is above normal. When MAP was reduced below normal in rats given constant infusions of ANG II the amount of water drunk and net fluid gain was proportional to the dose of ANG II but not the dose of diazoxide, the degree of hypotension, or urinary losses. This is consistent with previous reports that ANG II is essential for the drinking response to hypotension. Furthermore, it demonstrates that ANG II is not merely permissive but probably the signal controlling water intake when arterial pressure is reduced below normal.

Role of angiotensin in body fluid homeostasis of mice: effect of losartan on water and NaCl intakes

2005 ◽  
Vol 288 (3) ◽  
pp. R638-R644 ◽  
Author(s):  
Emily C. Crews ◽  
Neil E. Rowland
Keyword(s):  
Water Intake ◽  
Brain Regions ◽  
Ang Ii ◽  
Sodium Appetite ◽  
Low Sodium Diet ◽  
Low Sodium ◽  
Endogenous Production ◽  
Drinking Response

It is known that mice injected peripherally with ANG II do not show a drinking response but that cFos immunoreactivity (ir) is induced in brain regions similar to those in rats. We now show in Crl:CD1(ICR) mice that peripheral injection of the ANG II type 1 receptor antagonist losartan was sufficient to prevent this induction of Fos-ir in the subfornical organ (SFO). Injection of ANG II into the lateral cerebral ventricle produced a robust water intake in mice and induced Fos-ir in SFO, as well as in median preoptic (MnPO) and paraventricular (PVN) nuclei. Peripheral injection of losartan blocked this drinking response and prevented the induction of Fos-ir in each of these brain regions. Hypovolemia produced by polyethylene glycol (PEG) produced a robust water intake but no evidence of sodium appetite, and it induced Fos-ir in SFO, MnPO, and PVN. Peripheral injection of losartan did not affect this drinking response. Fos-ir induced by PEG in SFO and MnPO was reduced by treatment with losartan, while that induced in the PVN was further increased by losartan. Sodium depletion with furosemide and low-sodium diet produced a strong sodium appetite and induced Fos-ir in SFO and MnPO. Treatment with losartan completely blocked the sodium appetite, as well as the induction of Fos-ir in these brain regions. These data indicate that endogenous production of ANG II and action at forebrain receptors is critically involved in depletion-related sodium appetite in mice. The absence of an effect of losartan on PEG-induced drinking suggests the critical involvement of other factor(s) such as arterial or venous baroreceptor input, and we discuss how this factor could also explain why peripheral ANG II is not dipsogenic in mice.

Altered TP receptor function in isolated, perfused kidneys of nondiabetic and diabetic ApoE-deficient mice

2008 ◽  
Vol 294 (1) ◽  
pp. F120-F129 ◽  
Author(s):  
Frédéric Michel ◽  
Serge Simonet ◽  
Christine Vayssettes-Courchay ◽  
Florence Bertin ◽  
Patricia Sansilvestri-Morel ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Kidney Disease ◽  
Renal Diseases ◽  
Receptor Ligands ◽  
Tp Receptor ◽  
Vasodilator Activity ◽  
Tp Receptors ◽  
Apoe Ko Mice ◽  
Apoe Ko ◽  
Biphasic Responses

Early manifestations of kidney disease occur in atherosclerosis and activation of TP (thromboxane A2) receptors is implicated in atherosclerotic, diabetes, and renal diseases. The purpose of the present study was to analyze, in isolated, perfused mouse kidneys, the participation of TP receptors in renal vasoconstrictions and vasodilatations. In kidneys, taken from wild-type C57BL6, apolipoprotein E-deficient (ApoE-KO) and diabetic ApoE-KO mice, changes in perfusion pressure were recorded. Constrictions to TP receptor ligands U 46619, arachidonic acid, PGH2, and 8-iso-PGF2α, but not those to angiotensin II, endothelin, or norepinephrine, were inhibited by the selective TP receptor antagonist Triplion (S 18886; 10 nM). Acetylcholine and prostacyclin evoked biphasic responses during methoxamine constrictions; the constrictor part was blocked by Triplion. In ApoE-KO mouse kidneys, compared with C57BL6, a specific decrease in norepinephrine response and no modification in dilator responses were observed. In diabetic ApoE-KO mouse kidneys, constrictions to U 46619 and those to 8-iso-PGF2α were significantly and selectively augmented, without modification in the expression of the TP receptor, and again without any significant change in vasodilator activity. Thus TP receptors are functional, and their activation is not involved in norepinephrine, endothelin, and angiotensin II vasoconstrictions but is implicated in the unusual vasoconstrictions to acetylcholine and prostacyclin. Increased responsiveness of TP receptors occurs in diabetic ApoE-KO mouse kidneys. Thus early changes in TP receptor-mediated vasoconstrictor activity may participate in the development of kidney disease in atherosclerosis and diabetes.

Abstract 070: AntagomiR-762 Prevents Angiotensin II Induced Aortic Fibrosis and Stiffening

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Kim Ramil C Montaniel ◽  
Jing Wu ◽  
Matthew R Bersi ◽  
Liang Xiao ◽  
Hana A Itani ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Organ Damage ◽  
Matrix Proteins ◽  
Locked Nucleic Acid ◽  
Ang Ii ◽  
End Organ Damage ◽  
Acid Inhibitor ◽  
Vascular Stiffening ◽  
Aortic Stiffening

We and others have shown that hypertension (HTN) is associated with a striking deposition of collagen in the vascular adventitia. This causes vascular stiffening, which increases pulse wave velocity and contributes to end-organ damage. Through a screen of vascular microRNAs (miRNAs), we found that miR-762 is the most upregulated miRNA in mice with angiotensin II (Ang II)-induced HTN. qRT-PCR confirmed that miR-762 is upregulated 6.35±1.22 (p=0.03) fold in aortas of Ang II-infused mice compared with controls. This was a direct effect of Ang II, as miR-762 upregulation was not eliminated by lowering blood pressure with hydralazine and hydrochlorothiazide and was increased only 2-fold in DOCA salt HTN. To study the role of miR-762 in HTN, we administered a locked nucleic acid inhibitor of miR-762 (antagomiR-762). AntagomiR-762 administration did not alter the hypertensive response to Ang II, yet it normalized stress-strain relationships and aortic energy storage that occurs in systole (Table). Further studies showed that antagomiR-762 dramatically affected vascular matrix proteins, reducing mRNA for several collagens and fibronectin and dramatically upregulating collagenases MMP1a, 8 and 13 (Table). Thus, miR-762 has a major role in modulating vascular stiffening and its inhibition dramatically inhibits pathological fibrosis, enhances matrix degradation and normalizes aortic stiffness. AntagomiR-762 might represent a new approach to prevent aortic stiffening and its consequent end-organ damage.

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