Circulating angiotensin II mediates sodium appetite in adrenalectomized rats

2001 ◽  
Vol 281 (3) ◽  
pp. R723-R729 ◽  
Author(s):  
G. H. M. Schoorlemmer ◽  
A. K. Johnson ◽  
R. L. Thunhorst
Keyword(s):  
Intravenous Infusion ◽  
Sodium Intake ◽  
Peripheral Circulation ◽  
Ang Ii ◽  
Sodium Depletion ◽  
Sodium Appetite ◽  
Brain Ventricle ◽  
The Brain ◽  
Adrenalectomized Rats

We investigated the role of circulating ANG II in sodium appetite after adrenalectomy. Adrenalectomized rats deprived of their main access to sodium (0.3 M NaCl) for 9 h drank 14.1 ± 1.5 ml of the concentrated saline solution in 2 h of access. Intravenous infusion of captopril (2.5 mg/h) during the last 5 h of sodium restriction reduced sodium intake by 77 ± 12% ( n = 5) without affecting the degree of sodium depletion and hypovolemia incurred during deprivation. Functional evidence indicates that this dose of captopril blocked production of ANG II in the peripheral circulation, but not in the brain; that is, injection of ANG I into the lateral brain ventricle stimulated intake of both water and 0.3 M NaCl. Intravenous infusion of ANG II (starting 10–15 min before 0.3 M NaCl became available) in adrenalectomized, captopril-treated rats restored both sodium intake and blood pressure to values seen in rats not treated with captopril. Longer (20 h) infusions of captopril in 22-h sodium-restricted rats also blocked sodium appetite, but reduced or prevented sodium depletion. Intravenous infusion of ANG II after these long captopril infusions stimulated sodium intake, but intake was less than in controls not treated with captopril. These results indicate that most or all of the sodium appetite of adrenalectomized rats is mediated by circulating ANG II.

Role of angiotensin in body fluid homeostasis of mice: fluid intake, plasma hormones, and brain Fos

2003 ◽  
Vol 284 (6) ◽  
pp. R1586-R1594 ◽  
Author(s):  
Neil E. Rowland ◽  
Bradley E. Goldstein ◽  
Kimberly L. Robertson
Keyword(s):  
Plasma Renin ◽  
Brain Regions ◽  
Fluid Loss ◽  
Ang Ii ◽  
Sodium Appetite ◽  
Body Fluid Homeostasis ◽  
Cd1 Mice ◽  
Plasma Hormones ◽  
The Brain

CD1 mice injected peripherally with either ANG I or ANG II failed to drink substantial amounts of water or NaCl, yet showed strong Fos immunoreactivity (ir) in subfornical organ (SFO). Mice injected with furosemide showed modest stimulation of NaCl intake either 3 or 24 h later, were hypovolemic, and showed elevated plasma renin activity (PRA). The pattern of Fos-ir in the brain after furosemide was similar to that seen after peripheral injection of ANG II. Mice became hypovolemic after subcutaneous injection of polyethylene glycol (PEG), showed large increases in PRA, aldosterone, and water intake, but did not show sodium appetite. PEG-treated mice had strong activation of SFO as well as other brain regions previously shown to be related to ANG-associated drinking in rats. ANG II appears to have a modified role in the behavioral response to fluid loss in mice compared with rats.

Central infusion of the AT1 receptor antagonist losartan inhibits thirst but not sodium appetite in cattle

1997 ◽  
Vol 272 (6) ◽  
pp. R1940-R1945 ◽  
Author(s):  
J. R. Blair-West ◽  
D. A. Denton ◽  
M. J. McKinley ◽  
R. S. Weisinger
Keyword(s):  
Water Intake ◽  
Salt Intake ◽  
Sodium Intake ◽  
High Water ◽  
Salt Appetite ◽  
Ang Ii ◽  
Sodium Depletion ◽  
Water Restriction ◽  
Sodium Appetite ◽  
High Water Intake

Experiments in cattle compared the effects of intracerebroventricular (i.c.v.) infusions of losartan and PD-123319 on water intake caused by water restriction, i.c.v. infusion of hypertonic NaCl, or i.c.v. infusion of angiotensin II (ANG II). The effects of these receptor antagonists on sodium intake caused by sodium depletion were also examined. Losartan infusion caused dose-dependent inhibition of the high water intake caused by the physiological stimulus of water restriction or by ANG II infusion but did not affect salt appetite. PD-123319 infused at equimolar or greater (in ANG II experiments) doses did not affect water intake or salt intake due to sodium depletion. The results of these i.c.v. infusion experiments confirm our earlier proposal that the physiological regulation of water intake in cattle may be mediated by ANG II acting centrally via AT1 receptors. The dose of losartan that inhibited thirst in cattle did not inhibit sodium appetite, nor did an equimolar dose of PD-123319.

Abstract P059: A A Role of Aminopeptidase A in the Brain on Cardiovascular Regulation of Conscious Rat

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Takuto Nakamura ◽  
Masanobu Yamazato ◽  
Akio Ishida ◽  
Yusuke Ohya
Keyword(s):  
Blood Pressure ◽  
Protein Expression ◽  
Drinking Behavior ◽  
Cardiovascular Regulation ◽  
Ang Ii ◽  
Hypertensive Rats ◽  
Aminopeptidase A ◽  
The Brain

Objective: Aminopeptidase A (APA) have important role in conversion of Ang II to Ang III. Intravenous APA administration lowers blood pressure in hypertensive rats. In contrast, APA inhibition in the brain lowers blood pressure in hypertensive rats. Therefore APA might have different role on cardiovascular regulation. However, a role of APA and Ang III on cardiovascular regulation especially in the brain has not been fully understood. Our purpose of present study was to investigate a role of APA and Ang III in the brain on cardiovascular regulation in conscious state. Method: 12-13 weeks old Wistar Kyoto rat (WKY) and 12-16 weeks old spontaneously hypertensive rat (SHR) were used. i) APA distribution in the brain was evaluated by immunohistochemistry. Protein expression of APA was evaluated by Western blotting. Enzymatic activity of APA was evaluated using L-glutamic acid γ-(4-nitroanilide) as a substrate. ii) WKY received icv administration of Ang II 25ng/2μL and Ang III 25ng/2μL. We recorded change in mean arterial pressure (MAP) in conscious and unrestraied state and measured induced drinking time. iii) SHR received icv administeration of recombinant APA 400ng/4μL. We recorded change in MAP in conscious and unrestraied state and measured induced drinking time. Result: i) APA was diffusely immunostained in the cells of brain stem including cardiovascular regulatory area such as rostral ventrolateral medulla. Protein expression and APA activity in the brain were similar between WKY (n=3) and SHR (n=3).ii) Icv administration of Ang II increased MAP by 33.8±3.8 mmHg and induced drinking behavior for 405±90 seconds (n=4). Icv administration of Ang III also increased MAP by 24.7±2.4 mmHg and induced drinking behavior for 258±62 seconds (n=3). These vasopressor activity and induced drinking behavior was completely blocked by pretretment of angiotensin receptor type 1 blocker.iii) Icv administration of APA increased MAP by 10.0±1.7 mmHg (n=3). Conclusion: These results suggested that Ang III in the brain increase blood pressure by Angiotensin type 1 receptor dependent mechanism and APA in the brain may involved in blood pressure regulation as a vasopressor enzyme.

Abstract P152: Aminopeptidase A in the Brain Exerts Cardiovascular Action via Degradation of Kallidin to Bradykinin

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Takuto Nakamura ◽  
Masanobu Yamazato ◽  
Yusuke Ohya
Keyword(s):  
Blood Pressure ◽  
Pressor Response ◽  
Cardiovascular Regulation ◽  
Receptor Blocker ◽  
Ang Ii ◽  
Aminopeptidase A ◽  
Hoe 140 ◽  
Wistar Kyoto ◽  
The Brain

Objective: Aminopeptidase A (APA) degrades of various sympathomodulatory peptides such as angiotensin (Ang) II, cholecystkinin-8, neurokinin B and kallidin. APA activity is increased in the brain of hypertensive rats. A centrally acting APA inhibitor prodrug is currently under investigation in clinical trial for treatment of hypertension. In previous reports, a role of APA in the brain on cardiovascular regulation was researched focus on only renin-angiotensin system. We previously reported that intracerebroventricular(icv) administration of APA increased blood pressure and that this pressor response was partially blocked by angiotensin receptor blocker. In this study, we evaluated a role of APA on cardiovascular regulation focusing on peptides other than Ang II. Method: Eleven weeks old Wistar Kyoto rats were used. We icv administrated 800 ng/8 μL of APA after pretreatment of following drugs, i) 8μL of artificial cerebrospinal fluid (aCSF) as a control, ii) 80 nmol/8 μL of amastatin which is a non-specific aminopeptidase inhibitor, iii) 1 nmol/8 μL of HOE-140 which is a bradykinin receptor blocker to evaluate the involvement of degradation of kallidin to bradykinin by APA. Result: i) Icv administration of APA after pretreatment of aCSF increased blood pressure rapidly. Blood pressure reached a peak within 1 minute. The elevated blood pressure decreased gradually and reached baseline blood pressure in 10 minutes. A peak pressor response is 25.5±1.4 mmHg (n=5). ii) Icv pretreatment of amastatin or HOE-140 did not change the blood pressure. A peak pressor response induced by APA is 13.1±4.1 mmHg (n=6, p<0.05 vs aCSF). iii) Icv pretreatment of HOE-140 did not change the blood pressure. A peak pressor response induced by APA is 21.2±1.8 mmHg (n=4, p<0.05 vs aCSF). Conclusion: 1) Icv administration of APA increased blood pressure by APA enzymatic activity. 2) Cardiovascular regulation of APA in the brain is due to not only degradation of Ang II to Ang III but also degradation of kallidin to bradykinin. Clinical implication: We think inhibition of APA in the brain may be a unique therapeutic target which affects several cardiovascular peptides in the brain.

Dissociation in plasma renin and adrenal ANG II and aldosterone responses to sodium restriction in rats

1991 ◽  
Vol 261 (4) ◽  
pp. E487-E494 ◽  
Author(s):  
A. Menachery ◽  
L. M. Braley ◽  
I. Kifor ◽  
R. Gleason ◽  
G. H. Williams
Keyword(s):  
Plasma Renin ◽  
Fold Increase ◽  
Plasma Aldosterone ◽  
Delayed Response ◽  
Ang Ii ◽  
Sodium Restriction ◽  
Sodium Depletion ◽  
Pathway Activity

In rats, plasma renin activity (PRA) increases sharply, reaching a plateau within hours of sodium restriction. Plasma aldosterone increases gradually, not reaching a plateau for 1-2 days. To determine whether this dissociation is secondary to the time needed to modify adrenal sensitivity to angiotensin II (ANG II) and to assess the role of locally produced ANG II in this process, rats were salt restricted for 0-120 h. Plasma hormone levels were assessed, adrenal ANG II was measured, and basal and ANG II (1 x 10(-8) M)-stimulated steroidogenesis were determined in vitro. Although PRA attained an elevated plateau within 8 h, plasma aldosterone did not peak until after 48 h of sodium depletion. The in vitro aldosterone sensitivity to exogenous ANG II was not apparent until rats had been salt restricted for 16 h. A plateau (4-fold increase above the ANG II response on high salt) was achieved between 24 and 48 h. Adrenal ANG II also exhibited a similar delayed response that correlates significantly with changes in aldosterone biosynthesis and late pathway activity. Thus the dissociation between PRA and plasma aldosterone may be secondary to a lag in the zona glomerulosa's (ZG) steroidogenic response to ANG II as well as a parallel lag in tissue ANG II production, suggesting that changes in tissue ANG II may mediate ZG sensitivity to ANG II during sodium deprivation.

Effects of sodium depletion and angiotensin II on osmotic regulation of vasopressin

1986 ◽  
Vol 250 (2) ◽  
pp. R287-R291
Author(s):  
C. E. Wade ◽  
L. C. Keil ◽  
D. J. Ramsay
Keyword(s):  
Angiotensin Ii ◽  
Hypertonic Saline ◽  
Intravenous Infusion ◽  
Plasma Osmolality ◽  
Sodium Balance ◽  
Plasma Sodium ◽  
Ang Ii ◽  
Sodium Depletion ◽  
Relationship Of ◽  
The Relationship

After alterations in sodium balance, osmotic reactivity of vasopressin (AVP) release was evaluated in seven conscious dogs during bilateral intracarotid infusions of hypertonic saline. A low-sodium diet reduced plasma sodium concentration by 3%; deoxycorticosterone acetate (30 mg/day for 2 days) elevated the concentration by 1%. Neither treatment altered resting plasma AVP. Hypertonic intracarotid infusions increased jugular plasma osmolality by 20 +/- 2 mosmol/kg independent of manipulations. Plasma AVP values were significantly increased (P less than 0.05) in sodium-depleted dogs compared with values of the control animals. In addition, the osmotic reactivity of AVP release was evaluated during exogenous administration of angiotensin II (ANG II). Intravenous infusion of ANG II (5 ng . kg-1 . min-1) increased plasma concentration of ANG II but did not alter concentration of plasma AVP. The slope for the relationship of jugular plasma osmolality to plasma AVP during hypertonic intracarotid infusions was significantly increased with intravenous infusion of ANG II. Sodium depletion and intravenous ANG II potentiate the relationship of plasma osmolality and plasma AVP when evaluated with intracarotid hypertonic saline infusions in dogs.

Role of 20-hydroxyeicosatetraenoic acid in the renal and vasoconstrictor actions of angiotensin II

2002 ◽  
Vol 283 (1) ◽  
pp. R60-R68 ◽  
Author(s):  
Magdalena Alonso-Galicia ◽  
Kristopher G. Maier ◽  
Andrew S. Greene ◽  
Allen W. Cowley ◽  
Richard J. Roman
Keyword(s):  
Urinary Excretion ◽  
Intravenous Infusion ◽  
Pressor Response ◽  
Maximal Response ◽  
Epoxyeicosatrienoic Acids ◽  
Ang Ii ◽  
Hydroxyeicosatetraenoic Acid ◽  
Peripheral Vasculature ◽  
Oxide Synthase

The present study examined the effects of ANG II on the renal synthesis of 20-hydroxyeicosatetraenoic acid (20-HETE) and its contribution to the renal vasoconstrictor and the acute and chronic pressor effects of ANG II in rats. ANG II (10−11 to 10−7mol/l) reduced the diameter of renal interlobular arteries treated with inhibitors of nitric oxide synthase and cyclooxygenase, lipoxygenase, and epoxygenase by 81 ± 8%. Subsequent blockade of the synthesis of 20-HETE with 17-octadecynoic acid (1 μmol/l) increased the ED50 for ANG II-induced constriction by a factor of 15 and diminished the maximal response by 61%. Graded intravenous infusion of ANG II (5–200 ng/min) dose dependently increased mean arterial pressure (MAP) in thiobutylbarbitol-anesthetized rats by 35 mmHg. Acute blockade of the formation of 20-HETE with dibromododecenyl methylsulfimide (DDMS; 10 mg/kg) attenuated the pressor response to ANG II by 40%. An intravenous infusion of ANG II (50 ng · kg−1 · min−1) in rats for 5 days increased the formation of 20-HETE and epoxyeicosatrienoic acids (EETs) in renal cortical microsomes by 60 and 400%, respectively, and increased MAP by 78 mmHg. Chronic blockade of the synthesis of 20-HETE with intravenous infusion of DDMS (1 mg · kg−1 · h−1) or EETs and 20-HETE with 1-aminobenzotriazole (ABT; 2.2 mg · kg−1 · h−1) attenuated the ANG II-induced rise in MAP by 40%. Control urinary excretion of 20-HETE averaged 350 ± 23 ng/day and increased to 1,020 ± 105 ng/day in rats infused with ANG II (50 ng · kg−1 · min−1) for 5 days. In contrast, urinary excretion of 20-HETE only rose to 400 ± 40 and 600 ± 25 ng/day in rats chronically treated with ANG II and ABT or DDMS respectively. These results suggest that acute and chronic elevations in circulating ANG II levels increase the formation of 20-HETE in the kidney and peripheral vasculature and that 20-HETE contributes to the acute and chronic pressor effects of ANG II.

scholarly journals Role of ANG II in mediating somatosensory-induced renal nerve-dependent antinatriuresis in the rat

1998 ◽  
Vol 275 (1) ◽  
pp. R194-R202 ◽  
Author(s):  
Chunlong Huang ◽  
Edward J. Johns
Keyword(s):  
Sodium Excretion ◽  
Renal Perfusion ◽  
Urine Flow ◽  
Renal Nerves ◽  
Ang Ii ◽  
Renal Nerve ◽  
Somatosensory Stimulation ◽  
Two Stages ◽  
The Brain

This study examined the renal nerve-dependent renal hemodynamic and tubular responses to somatosensory stimulation in the anesthetized rat by use of subcutaneously applied capsaicin when the action of ANG II was blocked peripherally or selectively within the brain. Activation of skin somatosensory receptors caused a transient reversible 10–15% increase in blood pressure, and while renal perfusion pressure was regulated at control levels, there was a transient fall in urine flow and sodium excretion even though both renal blood flow and glomerular filtration rate were unchanged. These reflexly induced excretory responses were abolished when the renal nerves were sectioned. Administration of the ANG II AT1-receptor antagonist, losartan, either intravenously at 3 or 10 mg/kg or locally into the lateral cerebroventricles at 15 μg plus 7.5 μg/h, had no effect on capsaicin-induced vasopressor responses but blocked the reductions in urine flow and sodium excretion. These findings are consistent with ANG II being involved in at least two stages in the reflex, one centrally and one at the periphery.

Alterations in Cerebrospinal Fluid Angiotensin II by Sodium Intake in Patients with Essential Hypertension

1989 ◽  
Vol 77 (4) ◽  
pp. 389-394 ◽  
Author(s):  
Minoru Kawamura ◽  
Yuhei Kawano ◽  
Kaoru Yoshida ◽  
Masahito Imanishi ◽  
Satoshi Akabane ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Essential Hypertension ◽  
Sodium Intake ◽  
Ang Ii ◽  
Sodium Depletion ◽  
High Sodium ◽  
Sodium Diet ◽  
Low Sodium Diet ◽  
Low Sodium

1. Angiotensin (ANG) levels were measured in the cerebrospinal fluid of 15 patients with essential hypertension on a high sodium diet for 1 week and on a low sodium diet for a further week. ANGs were determined using a system of extraction by Sep-Pak cartridges followed by h.p.l.c. combined with radioimmunoassay. 2. Sodium depletion resulted in increases of ANG II in the cerebrospinal fluid from 1.16 ± 0.38 (sem) to 1.83 ± 0.43 fmol/ml (P < 0.01) and of ANG III from 0.65 ± 0.11 to 0.86 ± 0.15 fmol/ml (P < 0.01). 3. The ANG II level in the cerebrospinal fluid was found to be unchanged and recovery of added ANG II was approximately 90%, even after incubation for 3 h, on both diets. Thus, it is unlikely that ANG II is produced or degraded in the cerebrospinal fluid in vitro. 4. There was no significant correlation between the cerebrospinal fluid and the plasma ANG II concentration on the low sodium diet. 5. These results suggest that the cerebrospinal fluid ANG II level increases with sodium depletion, and that the effect of the level of ANG II on the activity of the angiotensin-forming system in the central nervous system may be assessed by determination of ANG II in the cerebrospinal fluid in patients with essential hypertension.

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