Sympathoexcitatory and pressor responses to increased brain sodium and ouabain are mediated via brain ANG II

1996 ◽  
Vol 270 (1) ◽  
pp. H275-H280 ◽  
Author(s):  
B. S. Huang ◽  
F. H. Leenen
Keyword(s):  
Pressor Response ◽  
Renin Angiotensin System ◽  
Sodium Concentration ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renal Sympathetic Nerve Activity ◽  
Fab Fragments ◽  
Pressor Responses ◽  
Before And After ◽  
The Brain

Intracerebroventricular administration of hypertonic saline, ouabain, brain ouabainlike activity (OLA), or angiotensin II (ANG II) causes sympathoexcitatory and pressor effects in rats. To clarify the possible interaction between increased brain sodium, brain OLA, and the brain renin-angiotensin system (RAS), increases in mean arterial pressure, heart rate (HR), and renal sympathetic nerve activity (RSNA) in response to intracerebroventricular 0.3 M NaCl, ouabain, and ANG II were recorded in conscious Wistar rats before and after intracerebroventricular pretreatment with the angiotensin-receptor (AT1) blocker losartan, antibody Fab fragments (Digibind), or, as control, gamma-globulins. These Fab fragments bind ouabain and brain OLA with high affinity. The arginine vasopressin (AVP) antagonist [d(CH2)5Tyr(Me)]AVP (30 micrograms/ kg) was injected intravenously before each intracerebroventricular injection. Intracerebroventricularly administered 0.3 M NaCl (3.8 mul/min for 10 min), ouabain (0.3 and 0.6 microgram), and ANG II (10 and 30 ng) caused similar pressor responses. However, the extent of HR and RSNA responses to ANG II was smaller than those to 0.3 M NaCl and ouabain. Intracerebroventricular losartan (10 and 20 micrograms) blocked responses to ANG II and 0.3 M NaCl and significantly attenuated the responses to ouabain (pressor response by 50-70%; RSNA and HR by 60-80%). In contrast, intracerebroventricular Fab fragments (66 micrograms) blocked only the responses to 0.3 M NaCl and ouabain and did not affect the responses to ANG II. These results suggest that an acute rise in brain sodium concentration increases brain OLA and the latter exerts its sympathoexcitatory and pressor effects at least partly via activation of the brain RAS.

scholarly journals Hypersensitivity to acute ANG II in female growth-restricted offspring is exacerbated by ovariectomy

2011 ◽  
Vol 301 (4) ◽  
pp. R1199-R1205 ◽  
Author(s):  
Norma B. Ojeda ◽  
Suttira Intapad ◽  
Thomas P. Royals ◽  
Joshua T. Black ◽  
John Henry Dasinger ◽  
...  
Keyword(s):  
Pressor Response ◽  
Renin Angiotensin System ◽  
Female Offspring ◽  
Ang Ii ◽  
Angiotensin System ◽  
Intact Control ◽  
Enhanced Sensitivity ◽  
Renal Hemodynamic ◽  
Pressor Responses ◽  
Before And After

Female growth-restricted offspring are normotensive in adulthood. However, ovariectomy induces a marked increase in mean arterial pressure (MAP) that is abolished by renin angiotensin system (RAS) blockade, suggesting RAS involvement in the etiology of hypertension induced by ovariectomy in adult female growth-restricted offspring. Blockade of the RAS also abolishes hypertension in adult male growth-restricted offspring. Moreover, sensitivity to acute ANG II is enhanced in male growth-restricted offspring. Thus, we hypothesized that an enhanced sensitivity to acute ANG II may contribute to hypertension induced by ovariectomy in female growth-restricted offspring. Female offspring were subjected to ovariectomy (OVX) or sham ovariectomy (intact) at 10 wk of age. Cardio-renal hemodynamic parameters were determined before and after an acute infusion of ANG II (100 ng·kg−1·min−1 for 30 min) at 16 wk of age in female offspring pretreated with enalapril (40 mg·kg−1·day−1 for 7 days). Acute ANG II induced a significant increase in MAP in intact growth-restricted offspring (155 ± 2 mmHg, P < 0.05) relative to intact control (145 ± 4 mmHg). Ovariectomy augmented the pressor response to ANG II in growth-restricted offspring (163 ± 2 mmHg, P < 0.05), with no effect in control (142 ± 2 mmHg). Acute pressor responses to phenylephrine did not differ in growth-restricted offspring relative to control, intact, or ovariectomized. Furthermore, renal hemodynamic responses to acute ANG II were significantly enhanced only in ovariectomized female growth-restricted offspring. Thus, these data suggest that enhanced responsiveness to acute ANG II is programmed by intrauterine growth restriction and that sensitivity to acute ANG II is modulated by ovarian hormones in female growth-restricted offspring.

Influence of brain renin-angiotensin system on renal sympathetic and cardiac baroreflexes in conscious rabbits

1991 ◽  
Vol 260 (3) ◽  
pp. H770-H778 ◽  
Author(s):  
P. K. Dorward ◽  
C. D. Rudd
Keyword(s):  
Enzyme Inhibitor ◽  
Renin Angiotensin System ◽  
Ang Ii ◽  
Transient Pressure ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Before And After ◽  
Conscious Rabbits ◽  
The Brain ◽  
Renal Sympathetic

The role of the brain renin-angiotensin system (RAS) in the baroreflex regulation of renal sympathetic nerve activity (RSNA) and heart rate (HR) was studied in conscious rabbits. RSNA and HR were recorded during slow ramp changes in mean arterial pressure (MAP) before and after intraventricular infusion of 1) angiotensin II (ANG II), 2) ANG II receptor antagonist, [Sar1,Ile8]ANG II, or 3) converting enzyme inhibitor (CEI, enalaprilat). Central ANG II increased resting MAP and RSNA by 10.6 +/- 0.9 mmHg and 21 +/- 7%, respectively, but did not alter HR. There was a marked increase of 107 +/- 15% in the maximum RSNA evoked by slowly lowering MAP. In contrast, maximum reflex tachycardia was only modestly elevated, and baroreflex inhibition of RSNA and HR during MAP rises was unaffected. Central [Sar1,Ile8]ANG II had no effect on RSNA or HR, either at rest or during baroreflex responses, while CEI slightly enhanced maximal reflex responses. Thus exogenous ANG II causes a powerful excitation of renal sympathetic motoneurons, the magnitude of which is revealed when tonic baroreceptor inhibition is removed during transient pressure falls. However, in quietly resting conscious rabbits, we found no evidence for a tonic influence of endogenous ANG II on these neurons, and the physiological stimuli required for their activation by the brain RAS remain to be found.

Regulation of blood pressure in pregnancy: pressor system blockade and stimulation

1990 ◽  
Vol 258 (5) ◽  
pp. H1559-H1572 ◽  
Author(s):  
Z. R. Pan ◽  
M. D. Lindheimer ◽  
J. Bailin ◽  
W. M. Barron
Keyword(s):  
Vascular Reactivity ◽  
Renin Angiotensin System ◽  
Ang Ii ◽  
Angiotensin System ◽  
Pressor Responses ◽  
Before And After ◽  
Alpha Blockade ◽  
Near Term ◽  
Regulation Of Blood Pressure ◽  
In Pregnancy

Contributions of the autonomic nervous system (ANS), renin-angiotensin system (RAS), and arginine vasopressin (AVP) to basal mean arterial pressure (MAP) were evaluated in near-term pregnant and virgin rats as follows. MAP and heart rate (HR) were measured before and after ganglionic, alpha-adrenoreceptor, RAS, and/or AVP blockade. In addition, pressor responses to angiotensin II (ANG II), norepinephrine, phenylephrine, or AVP were determined in ganglionic-blocked animals. In both groups decrements in MAP were greatest after ganglionic or alpha-blockade, intermediate after RAS blockade, and negligible after AVP-V1 antagonism ([d(CH2)5Tyr(Me)]AVP). Recovery of MAP was also similar in the two groups except after phentolamine when MAP and HR remained lower in gravid rats. Superimposition of RAS or AVP blockade during phentolamine infusion suggested that ANG II and AVP were less effective in supporting MAP during alpha-blockade in pregnancy. Pressor responses to ANG II and norepinephrine during ganglionic blockade were markedly blunted during pregnancy; however, those to phenylephrine and AVP were unchanged. We conclude that contributions of ANS, RAS, and AVP to basal MAP are similar in pregnant and virgin rats; neural mechanisms dominating in both groups. However, recovery during alpha-blockade is impaired during gestation, apparently due to blunted HR responses and decreased pressor contributions of ANG II and AVP. This may be explained, in part, by decreased vascular reactivity to ANG II, although a similar mechanism cannot be invoked for AVP.

Lack of interaction between a hypertonic NaCl stimulus and the brain renin-angiotensin system

1983 ◽  
Vol 244 (4) ◽  
pp. H471-H478 ◽  
Author(s):  
S. Takishita ◽  
C. M. Ferrario
Keyword(s):  
Renin Angiotensin System ◽  
Ang Ii ◽  
Central Administration ◽  
Nerve Activity ◽  
Renal Nerve ◽  
Vasopressin Release ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Before And After ◽  
The Brain

Sodium and the renin-angiotensin system (RAS) participate in the regulation of cardiovascular function, in part via activation of central nervous system (CNS) mechanisms. Because intraventricular (IVT) administration of either hypertonic sodium chloride (NaCl) or angiotensin II (ANG II) elicits similar effects (i.e., natriuresis, hypertension, increased drinking, and enhanced vasopressin release) a common and final pathway may be involved. With this in mind, we measured the effect of an IVT injection (third or lateral ventricle) of 0.6 M NaCl on postganglionic renal nerve activity (RNA) and blood pressure in morphine-pentobarbital-anesthetized dogs before and after blockade of the brain RAS with either captopril or [Sar1,Ile8]ANG II. Both vagus and carotid sinus nerves were cut to avoid impingement of the baroreceptor reflex on the measured variables. IVT injection of 0.6 M NaCl produced a prominent hypertensive response and tachycardia associated with a 59 +/- 9% increase in RNA. These changes were statistically significant (P less than 0.001), correlated with each other, and were abolished by administration of hexamethonium chloride (10 mg/kg iv). Blockade of central ANG II receptors with [Sar1,Ile8]ANG II was without effect. However, in dogs given IVT SQ 14,225, there was a slight increase in baseline RNA before injection of 0.6 M NaCl; in addition, both the pressor and heart rate responses to the stimulus of hypertonic NaCl were further augmented. These results demonstrate that central administration of hypertonic NaCl in baroreceptor-denervated dogs produces marked activation of sympathetic nerve activity via mechanisms other than activation of the brain RAS.

Abstract 421: The Subfornical Organ (SFO) Mediates CSF Na+ -induced Pressor Response via Activation of AT1 Receptors

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Missale A Tiruneh ◽  
Bing S Huang ◽  
Frans H Leenen
Keyword(s):  
Crucial Role ◽  
Major Part ◽  
Wistar Rats ◽  
Pressor Response ◽  
Electrolytic Lesion ◽  
Induced Responses ◽  
Ang Ii ◽  
At1 Receptors ◽  
Pressor Responses ◽  
The Brain

In salt-sensitive rats on high salt or rats with icv infusion of Na + , the increase in CSF [Na + ] leads to activation of the brain renin-angiotensin-aldosterone system and thereby to sympatho-excitation and hypertension. We tested whether the SFO and AT 1 receptors in the SFO play a crucial role in mediating the Na + -induced responses. In conscious Wistar rats, intra-SFO infusion of Na + -rich aCSF increased BP in a dose-related manner, whereas mannitol with the same osmolarity had no effects. Intra-SFO infusion of the AT 1 receptor blocker candesartan (cand.,10 μg) abolished pressor responses to intra-SFO infusion of Ang II (80 ng) or Na + -rich aCSF (0.45-0.6 M NaCl), and prevented 50% of the BP increase induced by icv infusion of Na + -rich aCSF (0.3 M NaCl, 4 μl/min for 6 min). In another set of Wistar rats, electrolytic lesion of the SFO prevented 50-65% of BP increases induced by icv infusion of Na + -rich aCSF or Ang II (5 ng/min). These data suggest that the SFO neurons are Na + -sensitive and via AT 1 receptors mediate a major part of the pressor response to CSF Na + . Data=means±SE (n=5-7). *p<.05 vs vehicle or sham lesion.

Brain “ouabain” and angiotensin II contribute to cardiac dysfunction after myocardial infarction

1999 ◽  
Vol 277 (5) ◽  
pp. H1786-H1792 ◽  
Author(s):  
Frans H. H. Leenen ◽  
Baoxue Yuan ◽  
Bing S. Huang
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Renin Angiotensin System ◽  
Volume Overload ◽  
Angiotensin System ◽  
Sympathetic Hyperactivity ◽  
Renin Angiotensin ◽  
Fab Fragments ◽  
The Brain

In chronic heart failure (CHF), sympathetic activity increases in parallel with the impairment of left ventricle (LV) function, and sympathetic hyperactivity has been postulated to contribute to the progression of heart failure. In the brain, compounds with ouabain-like activity (“ouabain,” for brevity) and the renin-angiotensin system contribute to sympathetic hyperactivity in rats with CHF after myocardial infarction (MI). In the present studies, we assessed whether, in rats, chronic blockade of brain “ouabain” or the brain renin-angiotensin system inhibits the post-MI LV dysfunction. In rats, an MI was induced by acute coronary artery ligation. At either 0.5 or 4 wk post-MI, chronic treatment with Fab fragments for blocking brain “ouabain” or with losartan for blocking brain AT1 receptors was started and continued until 8 wk post-MI using osmotic minipumps connected to intracerebroventricular cannulas. At 8 wk post-MI, in conscious rats, LV pressures were measured at rest and in response to volume and pressure overload, followed by LV passive pressure-volume curves in vitro. At 8 wk post-MI, control MI rats exhibited clear increases in LV end-diastolic pressure (LVEDP) at rest and in response to pressure and volume overload. LV pressure-volume curves in vitro showed a marked shift to the right. Intravenous administration of the Fab fragments or losartan at rates used for central blockade did not affect these parameters. In contrast, chronic central blockade with either Fab fragments or losartan significantly lowered LVEDP at rest (only in 0.5- to 8-wk groups) and particularly in response to pressure or volume overload. LV dilation, as assessed from LV pressure-volume curves, was also significantly inhibited. These results indicate that chronic blockade of brain “ouabain” or brain AT1 receptors substantially inhibits development of LV dilation and dysfunction in rats post-MI.

Natriuretic response to renal interstitial hydrostatic pressure during angiotensin II blockade

1994 ◽  
Vol 266 (1) ◽  
pp. F117-F119 ◽  
Author(s):  
J. A. Haas ◽  
J. C. Lockhart ◽  
T. S. Larson ◽  
T. Henrikson ◽  
F. G. Knox
Keyword(s):  
Angiotensin Ii ◽  
Hydrostatic Pressure ◽  
Sodium Excretion ◽  
Renin Angiotensin System ◽  
Urinary Sodium Excretion ◽  
Treated Group ◽  
Sodium Reabsorption ◽  
Ang Ii ◽  
Angiotensin System ◽  
Before And After

Increases in renal interstitial hydrostatic pressure (RIHP) increase urinary sodium excretion (UNaV). Experimentally increasing RIHP by direct renal interstitial volume expansion (DRIVE) has been shown to decrease proximal tubule sodium reabsorption. The purpose of the present study was to investigate whether the renin-angiotensin system modulates the natriuretic response to DRIVE. Unilateral nephrectomy and implantation of two polyethylene matrices were performed 3 wk before the acute experiment. Fractional sodium excretion (FENa), RIHP, and glomerular filtration rate (GFR) were measured before and after DRIVE in control rats (n = 9) and in rats receiving the angiotensin II (ANG II) receptor antagonist, losartan potassium (10 mg/kg i.v.; n = 10). DRIVE was achieved by infusing 100 microliters of 2.5% albumin solution directly into the renal interstitium. GFR remained unchanged by DRIVE in both groups. In control animals, DRIVE significantly increased both RIHP (delta 3.8 +/- 0.5 mmHg) and FENa (delta 0.92 +/- 0.19%). In the losartan-treated group, RIHP (delta 2.8 +/- 0.4 mmHg) and FENa (delta 1.93 +/- 0.41%) also significantly increased. The natriuretic response to DRIVE was significantly enhanced during ANG II receptor blockade compared with control animals (delta UNaV/delta RIHP = 2.01 +/- 0.67 vs. 0.44 +/- 0.17 mu eq.min-1 x mmHg-1, respectively; P < 0.05). These results suggest that the blockade of angiotensin enhances the natriuretic response to increased RIHP during DRIVE.

Characterization of the renin-angiotensin system in the turtle Pseudemys scripta

1984 ◽  
Vol 247 (1) ◽  
pp. R15-R23 ◽  
Author(s):  
M. D. Cipolle ◽  
J. E. Zehr
Keyword(s):  
Pressor Response ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Ang Ii ◽  
Freshwater Turtles ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Fourfold Increase ◽  
Inactive Form ◽  
Pseudemys Scripta

Studies were conducted in freshwater turtles Pseudemys scripta to define some characteristics of the renin-angiotensin system in this reptile. Dialyzed acid-treated kidney extract (1 g tissue per ml water) produced a prolonged pressor response in unanesthetized turtles, which was eliminated by boiling the extract or by pretreating the turtle with [Sar1, Ile8]angiotensin II. A rat pressor assay was employed because turtle angiotensin (ANG) was bound poorly by the anti-[Asp1, Ile5, His9]ANG I used in our radioimmunoassay. Kidney extract incubated with homologous plasma (pH 5.5 and 25 degrees C) produced a time-dependent pressor response in rats. The pressor activity of the product was eliminated by dialysis or by pretreating the rats with [Sar1, Ile8]ANG II. The pressor response in anesthetized turtles to ANG I was significantly reduced by captopril, whereas the ANG II response remained unchanged, thus demonstrating the presence of ANG-converting enzyme activity in these animals. We determined the velocity of turtle ANG formation at various dilutions of enzyme (kidney extract) or substrate (plasma). Turtle kidney extract incubated with homologous plasma displayed typical Michaelis-Menten kinetics. Finally we conducted experiments to determine whether a portion of turtle plasma renin exists in an inactive form. Trypsinization caused a slight increase in plasma renin activity (PRA), whereas acidification to pH 3.3 yielded a fourfold increase in PRA.

scholarly journals The Prorenin and (Pro)renin Receptor: New Players in the Brain Renin-Angiotensin System?

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Wencheng Li ◽  
Hua Peng ◽  
Dale M. Seth ◽  
Yumei Feng
Keyword(s):  
Renin Angiotensin System ◽  
Ang Ii ◽  
Future Perspectives ◽  
Vasopressin Release ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Treatment Of Hypertension ◽  
High Level ◽  
The Brain

It is well known that the brain renin-angiotensin (RAS) system plays an essential role in the development of hypertension, mainly through the modulation of autonomic activities and vasopressin release. However, how the brain synthesizes angiotensin (Ang) II has been a debate for decades, largely due to the low renin activity. This paper first describes the expression of the vasoconstrictive arm of RAS components in the brain as well as their physiological and pathophysiological significance. It then focus on the (pro)renin receptor (PRR), a newly discovered component of the RAS which has a high level in the brain. We review the role of prorenin and PRR in peripheral organs and emphasize the involvement of brain PRR in the pathogenesis of hypertension. Some future perspectives in PRR research are heighted with respect to novel therapeutic target for the treatment of hypertension and other cardiovascular diseases.

scholarly journals Controlled Hemorrhage Sensitizes Angiotensin II-Elicited Hypertension through Activation of the Brain Renin-Angiotensin System Independently of Endoplasmic Reticulum Stress

2022 ◽  
Vol 2022 ◽  
pp. 1-13
Author(s):  
Guo-Biao Wu ◽  
Hui-Bo Du ◽  
Jia-Yi Zhai ◽  
Si Sun ◽  
Jun-Ling Cui ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Protein Expression ◽  
Plasma Levels ◽  
Renin Angiotensin System ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Phenylbutyric Acid ◽  
The Brain

Hemorrhagic shock is associated with activation of renin-angiotensin system (RAS) and endoplasmic reticulum stress (ERS). Previous studies demonstrated that central RAS activation produced by various challenges sensitizes angiotensin (Ang) II-elicited hypertension and that ERS contributes to the development of neurogenic hypertension. The present study investigated whether controlled hemorrhage could sensitize Ang II-elicited hypertension and whether the brain RAS and ERS mediate this sensitization. Results showed that hemorrhaged (HEM) rats had a significantly enhanced hypertensive response to a slow-pressor infusion of Ang II when compared to sham HEM rats. Treatment with either angiotensin-converting enzyme (ACE) 1 inhibitor, captopril, or ACE2 activator, diminazene, abolished the HEM-induced sensitization of hypertension. Treatment with the ERS agonist, tunicamycin, in sham HEM rats also sensitized Ang II-elicited hypertension. However, blockade of ERS with 4-phenylbutyric acid in HEM rats did not alter HEM-elicited sensitization of hypertension. Either HEM or ERS activation produced a greater reduction in BP after ganglionic blockade, upregulated mRNA and protein expression of ACE1 in the hypothalamic paraventricular nucleus (PVN), and elevated plasma levels of Ang II but reduced mRNA expression of the Ang-(1-7) receptor, Mas-R, and did not alter plasma levels of Ang-(1-7). Treatment with captopril or diminazene, but not phenylbutyric acid, reversed these changes. No treatments had effects on PVN protein expression of the ERS marker glucose-regulated protein 78. The results indicate that controlled hemorrhage sensitizes Ang II-elicited hypertension by augmenting RAS prohypertensive actions and reducing RAS antihypertensive effects in the brain, which is independent of ERS mechanism.

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