SENSITIVE SITES IN THE BRAIN FOR THE BLOOD PRESSURE AND DRINKING RESPONSES TO ANGIOTENSIN II

1977 ◽  
pp. 325-356 ◽  
Author(s):  
M. Ian Phillips ◽  
W.E. Hoffman
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
The Brain

Central angiotensin II-induced responses in spontaneously hypertensive rats

1977 ◽  
Vol 232 (4) ◽  
pp. H426-H433 ◽  
Author(s):  
W. E. Hoffman ◽  
M. I. Phillips ◽  
P. G. Schmid
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Pressure Effects ◽  
Spontaneous Hypertension ◽  
Angiotensin System ◽  
Spontaneously Hypertensive ◽  
Vascular Responsiveness ◽  
Vascular Sensitivity ◽  
Wistar Kyoto ◽  
The Brain

The brain isorenin angiotensin system has been implicated in the development of spontaneous hypertension by several investigators. The experiments reported here were designed to test the responsiveness of unanesthetized spontaneous hypertensive (SH) rats to intracerebroventricular angiotensin II injections compared to Wistar-Kyoto (WK) normotensive controls. The results indicate that there is no difference between SH and WK animals in drinking responses or antidiuretic hormone release to central angiotensin II injections; however, an increased pressor responsiveness to intraventricular angiotensin II in SH as compared to WK was observed. The results of intravenous infusions of pressor substances in these experiments and reports by other investigators suggest that the increased blood pressure effects to central angiotensin are due to three possible factors: 1) increased vascular responsiveness of SH to vasoconstrictor substances in general, 2) increased vascular sensitivity of SH rats to sympathetic outflow, and 3) decreased baroreceptor reflexes to acute increases in blood pressure. We suggest that the brain isorenin-angiotensin system may be involved in spontaneous hypertension by increased production of angiotensin II or by activation of a potentiated sympathetic system, but not by a generalized increased sensitivity of brain receptors to central angiotensin.

Two Sites of Cardiovascular Action of Angiotensin II in the Brain of the Dog

1973 ◽  
Vol 44 (4) ◽  
pp. 417-420 ◽  
Author(s):  
P. L. Gildenberg ◽  
C. M. Ferrario ◽  
J. W. McCubbin
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Lateral Ventricle ◽  
Area Postrema ◽  
Pressor Response ◽  
Cerebral Ventricle ◽  
Vertebral Arteries ◽  
Adjacent Structures ◽  
The Brain ◽  
Lateral Cerebral Ventricle

1. Infusion of angiotensin into both vertebral arteries or into a lateral cerebral ventricle of dogs anaesthetized with morphine-chloralose elicited a centrally mediated rise in blood pressure. 2. Heat coagulation of the area postrema and immediately adjacent structures abolished the pressor response to infusion of angiotensin into the circulation of the vertebral arteries, but did not alter the pressor response when the peptide was delivered into a cerebral lateral ventricle; transection of the midbrain eliminated the latter response but not the former. 3. It is concluded that there are at least two areas in the dog's brain that respond to angiotensin by inducing a raised blood pressure.

Abstract P231: Offspring of Captopril Treated Spontaneously Hypertensive Rats Have Lower Angiotensin II Type 1 Receptor Expression Which is Associated With Lower Blood Pressure

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
J X Masjoan-Juncos ◽  
Tang-Dong Liao ◽  
Ginette Bordcoch ◽  
Cesar A Romero ◽  
Oscar A Carretero
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Posterior Wall ◽  
Receptor Expression ◽  
Shr Rats ◽  
Spontaneously Hypertensive ◽  
Intracerebroventricular Infusion ◽  
Lower Blood ◽  
The Brain

It has been reported that SHR rats receiving angiotensin converting enzyme (ACE) inhibitor Captopril decrease blood pressure (BP) in at least two generation after the treatment was stopped. A decreased response to an intracerebroventricular infusion angiotensin I and angiotensin II in treated animals and their offspring was reported; however there is no reported mechanism that explains the changes observed in the untreated offspring of the Captopril treated animals. We hypothesize that captopril reduces angiotensin II type 1 receptor (AT1R) expression in CNS of the offspring of SHR rats treated with captopril. Animal groups are as follows: control animals, captopril treated animals, offspring of the control animals, offspring of the treated animals where the mother was removed from the treatment immediately after giving birth and Offspring of treated animals where the mother was removed from the treatment at weaning. BP was measured by intra-arterial method and Tail cuff. AT1R expression was measured in brain tissue using the posterior wall of the forth ventricle, as well as the top half of the brain stem. BP was different between treated groups and their offspring vs. control (Table 1). AT1R expression was significantly reduced in both offspring groups of the treated animals, when compared to control (Table 1). Therefore we conclude that captopril reduces blood pressure in the offspring of captopril treated SHR rats and that associates with a decrease in AT1R expression in CNS. Further research is necessary to determine the possible epigenetic mechanisms involved in AT1R reduction.

Angiotensin II attenuates baroreflexes at nucleus tractus solitarius of rats

1986 ◽  
Vol 250 (2) ◽  
pp. R193-R198 ◽  
Author(s):  
R. Casto ◽  
M. I. Phillips
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Baroreflex Sensitivity ◽  
Nucleus Tractus Solitarius ◽  
Ang Ii ◽  
Spontaneously Hypertensive ◽  
Baroreceptor Reflexes ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
The Brain

Microinjection of angiotensin II (ANG II) into the nucleus tractus solitarius (NTS) has been shown to produce a dose-dependent increase in blood pressure and heart rate. We have tested the effect of subpressor infusions of ANG II (10 ng . kg-1 . min-1) in the NTS on reflex bradycardia after intravenous administration of the vasoconstrictor phenylephrine (1-12 micrograms) in normotensive urethan-anesthetized rats. ANG II within the brain is thought to contribute to the decreased baroreflex sensitivity in spontaneously hypertensive rats (SHR). The sensitivity of the baroreflex was significantly decreased by the infusion of ANG II (1.01 +/- 0.08) compared with control (2.41 +/- 0.51) in the normotensive animals. Baroreflex sensitivity was significantly decreased in SHR (0.40 +/- 0.21) compared with normotensive animals. We conclude that ANG II within the NTS can inhibit the function of baroreceptor reflexes in normotensive animals, suggesting that the endogenous peptide may perform an inhibitory role in the baroreflex arc, and this is further evidence that central ANG II is involved in blood pressure of SHR.

scholarly journals β-Arrestin–Biased Agonist Targeting the Brain AT 1 R (Angiotensin II Type 1 Receptor) Increases Aversion to Saline and Lowers Blood Pressure in Deoxycorticosterone Acetate–Salt Hypertension

Hypertension ◽  
2020 ◽  
Author(s):  
Mario Zanaty ◽  
Fernando A.C. Seara ◽  
Pablo Nakagawa ◽  
Guorui Deng ◽  
Natalia M. Mathieu ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Central Administration ◽  
Deoxycorticosterone Acetate ◽  
Intracerebroventricular Infusion ◽  
Salt Hypertension ◽  
Saline Solutions ◽  
The Brain ◽  
Biased Agonist

Activation of central AT 1 Rs (angiotensin type 1 receptors) is required for the increased blood pressure, polydipsia, and salt intake in deoxycorticosterone acetate (DOCA)–salt hypertension. TRV120027 (TRV027) is an AT 1 R-biased agonist that selectively acts through β-arrestin. We hypothesized that intracerebroventricular administration of TRV027 would ameliorate the effects of DOCA-salt. In a neuronal cell line, TRV027 induced AT 1a R internalization through dynamin and clathrin-mediated endocytosis. We next evaluated the effect of chronic intracerebroventricular infusion of TRV027 on fluid intake. We measured the relative intake of water versus various saline solutions using a 2-bottle choice paradigm in mice subjected to DOCA with a concomitant intracerebroventricular infusion of either vehicle, TRV027, or losartan. Sham mice received intracerebroventricular vehicle without DOCA. TRV027 potentiated DOCA-induced water intake in the presence or absence of saline. TRV027 and losartan both increased the aversion for saline—an effect particularly pronounced for highly aversive saline solutions. Intracerebroventricular Ang (angiotensin) II, but not TRV027, increased water and saline intake in the absence of DOCA. In a separate cohort, blood pressure responses to acute intracerebroventricular injection of vehicle, TRV, or losartan were measured by radiotelemetry in mice with established DOCA-salt hypertension. Central administration of intracerebroventricular TRV027 or losartan each caused a significant and similar reduction of blood pressure and heart rate. We conclude that administration of TRV027 a selective β-arrestin biased agonist directly into the brain increases aversion to saline and lowers blood pressure in a model of salt-sensitive hypertension. These data suggest that selective activation of AT 1 R β-arrestin pathways may be exploitable therapeutically.

Indirect hypertensive actions of long-term intracarotid angiotensin II infusion during ovine pregnancy

1994 ◽  
Vol 72 (4) ◽  
pp. 311-316 ◽  
Author(s):  
S. C. Mukaddam-Daher ◽  
G. W. Aberdeen ◽  
S. C. Cha ◽  
J. Gutkowska ◽  
B. S. Nuwayhid ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Urine Volume ◽  
Plasma Renin ◽  
Sodium Balance ◽  
Angiotensin System ◽  
The Central Nervous System ◽  
The Brain ◽  
Internal Carotid Arteries

Angiotensin II (AngII) influences the regulation of mean arterial pressure (MAP) through numerous mechanisms, including an action of circulating AngII on the brain to alter autonomic activity. We have obtained evidence that the relative importance of this effect is increased during pregnancy. Consequently, these studies were undertaken to assess the effects of bilateral infusion of AngII (0.35 ng∙kg−1∙min−1∙artery−1) into the internal carotid arteries (ica) of sheep for 13 days. Six nonpregnant (NP) and six 105- to 125-day pregnant (PG) ewes were maintained in large metabolism cages, where MAP was continuously monitored. By day 10 of ica AngII infusion in NP ewes, MAP was increased from 83.9 ± 1.6 to 92.9 ± 2.8 mmHg (1 mmHg = 133.3 Pa) (p = 0.001). Twenty-four hour urine volume (UV, 2664 ± 341 to 1583 ± 228 mL; p = 0.005) and sodium excretion (UNaV, 190 ± 5 to 113 ± 19 mmol/day; p = 0.005) were decreased. 51Cr-tagged blood volume (BV) was increased on day 13 (3643 ± 187 to 4379 ± 446 mL; p = 0.05). In contrast, by only day 6 of ica AngII infusion in PG ewes, MAP increased from 79.1 ± 1.9 to 84.1 ± 1.4 mmHg (p = 0.03) in association with a BV expansion from 3999 ± 274 to 4207 ± 275 mL. These changes were preceded by decreases in UV (2813 ± 413 to 2198 ± 362 mL; p = 0.01) and UNaV (190 ± 15 to 118 ± 26 mmol/day; p = 0.01). By day 13, MAP had plateaued at 93.0 ± 1.2 mmHg. There were no changes in plasma AngII, plasma renin activity, arginine vasopressin, and atrial natriuretic factor during ica AngII infusion in either NP or PG ewes, suggesting that these effects are mediated via the central nervous system. Moreover, the data suggest that MAP is increased secondary to volume expansion associated with sodium and water retention. This effect appears to be more readily exhibited during pregnancy. Furthermore, this study demonstrates the importance of the rennin–angiotensin system in blood pressure homeostasis by actions other than direct vasoconstriction.Key words: angiotensin II, blood pressure, hypertension, sheep, pregnancy, sodium balance.

Abstract WP309: Hypertensive Stimuli Promote Brain Inflammation and Cognitive Impairment in a Pressure-Dependent Manner

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Christopher G Sobey ◽  
Quynh Nhu Dinh ◽  
Antony Vinh ◽  
Grant R Drummond ◽  
Michael De Silva
Keyword(s):  
Blood Pressure ◽  
Cognitive Impairment ◽  
Angiotensin Ii ◽  
Recognition Memory ◽  
Immune Cell ◽  
Brain Inflammation ◽  
Dependent Manner ◽  
Ang Ii ◽  
Cell Numbers ◽  
The Brain

Background: Hypertension increases the risk for stroke and cognitive impairment, and is strongly associated with inflammation of the vasculature and kidneys. However, it is unclear whether there is inflammation and immune cell infiltration in the brain during hypertension. Aims: To test whether chronic infusion of angiotensin II causes brain inflammation and cognitive dysfunction, and whether its effects are blood pressure-dependent. Methods: Male C57Bl/6 mice were administered vehicle or angiotensin II (Ang II, 0.7 mg/kg/d s.c. ) via osmotic minipumps. A subset of mice also received hydralazine (50 mg/kg) in their drinking water after minipump implantation. We measured systolic blood pressure by tail cuff plethysmography, immune cell numbers using flow cytometry and recognition memory using the novel object recognition test. Results: Ang II infusion increased blood pressure and promoted accumulation of leukocytes in the brain, including neutrophils, monocytes, T cells and B cells, all of which were elevated by ~2.5-fold compared to vehicle-treated mice (n=6-8, P<0.05). Co-administration of hydralazine prevented the pressor response to Ang II and reduced neutrophil and monocyte infiltration (n=7-8, P<0.05), however, hydralazine had no effect on T or B cell numbers (n=7-8). Ang II impaired recognition memory and this was prevented by administration of hydralazine (n=11-12, P<0.05). Conclusions: Our data indicate that inflammation occurs in the brain during Ang II-dependent hypertension and this is associated with impaired recognition memory. Reducing blood pressure reversed these effects. Chronic brain inflammation may be a contributing factor to the increased stroke risk and cognitive impairment during hypertension and may be mitigated by blood pressure reduction.

scholarly journals Angiotensin II-Induced Hypertension Is Attenuated by Overexpressing Copper/Zinc Superoxide Dismutase in the Brain Organum Vasculosum of the Lamina Terminalis

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
John P. Collister ◽  
Heather Taylor-Smith ◽  
Donna Drebes ◽  
David Nahey ◽  
Jun Tian ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Superoxide Dismutase ◽  
Angiotensin Ii ◽  
Intracellular Signaling ◽  
Lamina Terminalis ◽  
Copper Zinc Superoxide Dismutase ◽  
Zinc Superoxide Dismutase ◽  
Copper Zinc ◽  
Organum Vasculosum ◽  
The Brain

Angiotensin II (AngII) can access the brain via circumventricular organs (CVOs), including the subfornical organ (SFO) and organum vasculosum of the lamina terminalis (OVLT), to modulate blood pressure. Previous studies have demonstrated a role for both the SFO and OVLT in the hypertensive response to chronic AngII, yet it is unclear which intracellular signaling pathways are involved in this response. Overexpression of copper/zinc superoxide dismutase (CuZnSOD) in the SFO has been shown to attenuate the chronic hypertensive effects of AngII. Presently, we tested the hypothesis that elevated levels of superoxide (O2∙-) in the OVLT contribute to the hypertensive effects of AngII. To facilitate overexpression of superoxide dismutase, adenoviral vectors encoding human CuZnSOD or control adenovirus (AdEmpty) were injected directly into the OVLT of rats. Following 3 days of control saline infusion, rats were intravenously infused with AngII (10 ng/kg/min) for ten days. Blood pressure increased33±8 mmHg in AdEmpty rats (n=6), while rats overexpressing CuZnSOD (n=8) in the OVLT demonstrated a blood pressure increase of only18±5 mmHg after 10 days of AngII infusion. These results support the hypothesis that overproduction ofO2∙-in the OVLT plays an important role in the development of chronic AngII-dependent hypertension.

Angiotensin II and bradykinin: interactions between two centrally active peptides

1983 ◽  
Vol 244 (2) ◽  
pp. R285-R291 ◽  
Author(s):  
R. E. Lewis ◽  
W. E. Hoffman ◽  
M. I. Phillips
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Pressor Response ◽  
Common Mechanism ◽  
Ang Ii ◽  
Active Peptides ◽  
Central Actions ◽  
Prostaglandin A2 ◽  
The Brain ◽  
Peptide Interaction

Two neuropeptides, bradykinin (BK) and angiotensin II (ANG II), produce an increase in blood pressure when injected into the brain ventricles. This study is an example of central peptide-peptide interaction and was carried out to determine if BK and ANG II share a common mechanism in the brain to control blood pressure and drinking in rats. Prior injection of saralasin [10 micrograms intraventricularly (ivt)] was found to enhance the pressor response to ivt BK (5 micrograms) by 44%. The same dose of saralasin attenuated the pressor response to ivt ANG II (200 ng) by 55%. 50 ng ANG II and 5 micrograms BK given together ivt did not significantly alter blood pressure or urine conductance compared to 50 ng ANG II alone. Drinking to ivt infusions of ANG II (14 ng/min) was significantly attenuated when combined with BK (0.7 micrograms or 2.8 micrograms/min). Pretreatment with 10 micrograms indomethacin ivt diminished the pressor response to 5 micrograms ivt BK. Prostaglandin E2 (1.4 micrograms/min), but not prostaglandin A2, inhibited drinking to 14 ng/min ivt infusions of ANG II. The results suggest that ANG II and BK share an interrelationship with respect to their central actions: ANG II inhibits the BK pressor response and BK acts to inhibit drinking induced by ANG II. Prostaglandins of the E series may mediate these central actions of bradykinins.

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