scholarly journals EXPRESSION OF COMPONENTS OF THE RENIN‐ANGIOTENSIN SYSTEM IN THE BRAIN OF 2K1C HYPERTENSIVE RATS AFTER EXERCISE TRAINING

2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
Luiza Michelle Cangussu ◽  
Robson AS Santos ◽  
Almir Martins ◽  
Andreia Carvalho Alzamora ◽  
Maria Jose Campagnole‐Santos
Keyword(s):  
Exercise Training ◽  
Renin Angiotensin System ◽  
Hypertensive Rats ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
The Brain

A new strategy for treating hypertension by blocking the activity of the brain renin–angiotensin system with aminopeptidase A inhibitors

2014 ◽  
Vol 127 (3) ◽  
pp. 135-148 ◽  
Author(s):  
Ji Gao ◽  
Yannick Marc ◽  
Xavier Iturrioz ◽  
Vincent Leroux ◽  
Fabrice Balavoine ◽  
...  
Keyword(s):  
Antihypertensive Agents ◽  
Renin Angiotensin System ◽  
Site Directed Mutagenesis ◽  
Hypertensive Rats ◽  
Vasopressin Release ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Obesity And Diabetes ◽  
Aminopeptidase A ◽  
The Brain

Hypertension affects one-third of the adult population and is a growing problem due to the increasing incidence of obesity and diabetes. Brain RAS (renin–angiotensin system) hyperactivity has been implicated in the development and maintenance of hypertension in several types of experimental and genetic hypertension animal models. We have identified in the brain RAS that APA (aminopeptidase A) and APN (aminopeptidase N), two membrane-bound zinc metalloproteases, are involved in the metabolism of AngII (angiotensin II) and AngIII (angiotensin III) respectively. The present review summarizes the main findings suggesting that AngIII plays a predominant role in the brain RAS in the control of BP (blood pressure). We first explored the organization of the APA active site by site-directed mutagenesis and molecular modelling. The development and the use in vivo of specific and selective APA and APN inhibitors EC33 and PC18 respectively, has allowed the demonstration that brain AngIII generated by APA is one of the main effector peptides of the brain RAS, exerting a tonic stimulatory control over BP in conscious hypertensive rats. This identified brain APA as a potential therapeutic target for the treatment of hypertension, which has led to the development of potent orally active APA inhibitors, such as RB150. RB150 administered orally in hypertensive DOCA (deoxycorticosteroneacetate)-salt rats or SHRs (spontaneously hypertensive rats) crosses the intestinal, hepatic and blood–brain barriers, enters the brain, generates two active molecules of EC33 which inhibit brain APA activity, block the formation of brain AngIII and normalize BP for several hours. The decrease in BP involves two different mechanisms: a decrease in vasopressin release into the bloodstream, which in turn increases diuresis resulting in a blood volume reduction that participates in the decrease in BP and/or a decrease in sympathetic tone, decreasing vascular resistance. RB150 constitutes the prototype of a new class of centrally acting antihypertensive agents and is currently being evaluated in a Phase Ib clinical trial.

scholarly journals Regulation of brain renin-angiotensin system by benzamil-blockable sodium channels

1999 ◽  
Vol 276 (5) ◽  
pp. R1416-R1424 ◽  
Author(s):  
Masato Nishimura ◽  
Ken Ohtsuka ◽  
Naoharu Iwai ◽  
Hakuo Takahashi ◽  
Manabu Yoshimura
Keyword(s):  
Sodium Channels ◽  
Renin Angiotensin System ◽  
Hypertensive Rats ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Intracerebroventricular Infusion ◽  
Pcr Method ◽  
The Brain ◽  
Renal Hypertensive Rats

Changes in the renin-angiotensin system (RAS) mRNAs in the brain and the kidney of rats after administration of DOCA and/or sodium chloride were assessed by use of a competitive PCR method. Benzamil, a blocker of amiloride-sensitive sodium channels, was infused intracerebroventricularly or intravenously for 7 days in DOCA-salt or renal hypertensive rats, and the effects of benzamil on the brain RAS mRNAs were determined. Renin and ANG I-converting enzyme (ACE) mRNAs were not downregulated in the brain of rats administered DOCA and/or salt; however, these mRNAs were decreased in the kidney. Intracerebroventricular infusion of benzamil decreased renin, ACE, and ANG II type 1 receptor mRNAs in the brain of DOCA-salt hypertensive rats but not in the brain of renal hypertensive rats. The gene expression of the brain RAS, particularly renin and ACE, is regulated differently between the brain and the kidney in DOCA-salt hypertensive rats, and benzamil-blockable brain sodium channels may participate in the regulation of the brain RAS mRNAs.

scholarly journals EXERCISE TRAINING INDUCES CHANGES IN THE RENIN‐ANGIOTENSIN SYSTEM TOWARDS ANG‐(1–7)/ACE2/MAS AXIS IN THE HYPOTHALAMUS OF RENOVASCULAR HYPERTENSIVE RATS

2012 ◽  
Vol 26 (S1) ◽  
Author(s):  
Luiza Michelle Cangussu ◽  
Luzia M Oliveira ◽  
Jose R Silva ◽  
Andreia C Alzamora ◽  
Robson AS Santos ◽  
...  
Keyword(s):  
Exercise Training ◽  
Renin Angiotensin System ◽  
Hypertensive Rats ◽  
Angiotensin System ◽  
Renin Angiotensin

Role of the Brain Iso-Renin-Angiotensin System in Experimental Hypertension in Rats

1981 ◽  
Vol 61 (2) ◽  
pp. 175-180 ◽  
Author(s):  
Hiromichi Suzuki ◽  
Kazuoki Kondo ◽  
Michiko Handa ◽  
Takao Saruta
Keyword(s):  
Blood Pressure ◽  
Plasma Renin Activity ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Renin Activity ◽  
Cerebral Ventricles ◽  
Hypertensive Rats ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
The Brain

1. To examine the possible participation of the brain iso-renin-angiotensin system in the control of blood pressure, as well as in the regulation of plasma renin activity, saralasin and captopril were injected into the cerebral ventricles of three types of experimental hypertensive rats with different plasma renin profiles. 2. Injection of saralasin and captopril into the cerebral ventricles resulted in a significant decrease in blood pressure of two-kidney, one-clip Goldblatt hypertensive rats (11 ± 2 and 9 ± 3 mmHg respectively) and that of spontaneously hypertensive rats (13 ± 2 and 12 ± 2 mmHg respectively), but in deoxycorticosterone (DOC)-salt hypertensive rats injection of these two agents showed a significant increase in blood pressure (13 ± 2 and 12 ± 3 mmHg respectively). 3. The plasma renin activity was markedly decreased after injection of saralasin and captopril into the cerebral ventricles of two-kidney, one-clip Goldblatt hypertensive rats. Conversely, in DOC-salt hypertensive rats, the plasma renin activity was markedly increased after injection of these two agents. In spontaneously hypertensive rats these agents caused no significant change in plasma renin activity. 4. These findings suggest that the brain iso-renin-angiotensin system participates in the central regulation of blood pressure and may be responsible for modulation of the peripheral renin-angiotensin system.

Significance of the Brain Renin—Angiotensin System in Spontaneously Hypertensive Rats

1982 ◽  
Vol 63 (s8) ◽  
pp. 159s-161s ◽  
Author(s):  
Jeroen A. D. M. Tonnaer ◽  
Joke J. van Put ◽  
Victor M. Wiegant ◽  
Wybren de Jong
Keyword(s):  
Spontaneously Hypertensive Rats ◽  
Spontaneously Hypertensive Rat ◽  
Renin Angiotensin System ◽  
Hypotensive Effect ◽  
Sympathetic Outflow ◽  
Hypertensive Rats ◽  
Angiotensin System ◽  
Spontaneously Hypertensive ◽  
Renin Angiotensin ◽  
The Brain

1. The renin inhibitor N-acetyl-pepstatin was infused for 14 days or 5 days into the cerebral ventricular system of young and adult spontaneously hypertensive rats respectively. 2. The blood pressure and heart rate of the young animals was significantly lower as a result of this treatment, whereas the pressure of the adult animals tended to decrease. 3. The mechanism involved in the hypotensive effect of N-acetyl-pepstatin appeared to be independent of the peripheral renin-angiotensin system. The possible involvement of a decreased sympathetic outflow is suggested. 4. The present data indicate that the brain renin-angiotensin system contributes to the development of hypertension in the spontaneously hypertensive rat.

scholarly journals Exercise Training Improves the Altered Renin-Angiotensin System in the Rostral Ventrolateral Medulla of Hypertensive Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Chang-zhen Ren ◽  
Ya-Hong Yang ◽  
Jia-cen Sun ◽  
Zhao-Tang Wu ◽  
Ru-Wen Zhang ◽  
...  
Keyword(s):  
Exercise Training ◽  
Renin Angiotensin System ◽  
Cardiovascular Responses ◽  
Rostral Ventrolateral Medulla ◽  
Ventrolateral Medulla ◽  
Ang Ii ◽  
Hypertensive Rats ◽  
Blood Pressure Elevation ◽  
Angiotensin System ◽  
Renin Angiotensin

The imbalance between angiotensin II (Ang II) and angiotensin 1–7 (Ang 1–7) in the brain has been reported to contribute to cardiovascular dysfunction in hypertension. Exercise training (ExT) is beneficial to hypertension and the mechanism is unclear. This study was aimed to determine if ExT improves hypertension via adjusting renin angiotensin system in cardiovascular centers including the rostral ventrolateral medulla (RVLM). Spontaneously hypertensive rats (SHR, 8 weeks old) were subjected to low-intensity ExT or kept sedentary (Sed) for 12 weeks. Blood pressure elevation coupled with increase in age was significantly decreased in SHR received ExT compared with Sed. The results in vivo showed that ExT significantly reduced or increased the cardiovascular responses to central application of sarthran (antagonist of Ang II) or A779 (antagonist of Ang 1–7), respectively. The protein expression of the Ang II acting receptor AT1R and the Ang 1–7 acting receptor Mas in the RVLM was significantly reduced and elevated in SHR following ExT, respectively. Moreover, production of reactive oxygen species in the RVLM was significantly decreased in SHR following ExT. The current data suggest that ExT improves hypertension via improving the balance of Ang II and Ang 1–7 and antioxidative stress at the level of RVLM.

scholarly journals Sympathoexcitation Associated with Renin-Angiotensin System in Metabolic Syndrome

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Takuya Kishi ◽  
Yoshitaka Hirooka
Keyword(s):  
Metabolic Syndrome ◽  
Animal Studies ◽  
Renin Angiotensin System ◽  
Hypertensive Rats ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Ras Activation ◽  
Sympathetic Nervous ◽  
The Brain

Renin-angiotensin system (RAS) is activated in metabolic syndrome (MetS), and RAS inhibitors are preferred for the treatments of hypertension with MetS. Although RAS activation is important for the therapeutic target, underlying sympathetic nervous system (SNS) activation is critically involved and should not be neglected in the pathogenesis of hypertension with MetS. In fact, previous studies have suggested that SNS activation has the interaction with RAS activation and/or insulin resistance. As a novel aspect connecting the importance of SNS and RAS activation, we and other investigators have recently demonstrated that angiotensin II type 1 receptor (AT1R) blockers (ARBs) improve SNS activation in patients with MetS. In the animal studies, SNS activation is regulated by the AT1R-induced oxidative stress in the brain. We have also demonstrated that orally administered ARBs cause sympathoinhibition independent of the depressor effects in dietary-induced hypertensive rats. Interestingly, these benefits on SNS activation of ARBs in clinical and animal studies are not class effects of ARBs. In conclusion, SNS activation associated with RAS activation in the brain should be the target of the treatment, and ARBs could have the potential benefit on SNS activation in patients with MetS.

Central renin-angiotensin system and the pathogenesis of DOCA-salt hypertension in rats

1986 ◽  
Vol 251 (2) ◽  
pp. H261-H268 ◽  
Author(s):  
Y. Itaya ◽  
H. Suzuki ◽  
S. Matsukawa ◽  
K. Kondo ◽  
T. Saruta
Keyword(s):  
Blood Pressure ◽  
Fluid Intake ◽  
Renin Angiotensin System ◽  
Hypertensive Rats ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Plasma Vasopressin ◽  
Baroreceptor Reflexes ◽  
Salt Hypertension ◽  
The Brain

The antihypertensive effect of blockade of the brain renin-angiotensin system (brain RAS) was investigated in DOCA (deoxycorticosterone acetate)-salt hypertensive rats. Continuous intracerebroventricular (ICV) administration of SQ14225 (SQ; 1.25 micrograms X 0.5 microliter-1 X h-1) for 7 days attenuated the increase in blood pressure (99 +/- 5 vs. 116 +/- 4 mmHg on the 7th day) and also reduced the elevation of blood pressure (157 +/- 7 vs. 138 +/- 6 mmHg) in these hypertensive rats. Attenuation of increasing blood pressure in the developing phase following ICV SQ treatment was accompanied by decrease of fluid intake and prevention of elevation of the plasma vasopressin. In the established phase, in addition to reduction of the plasma vasopressin and decrease of fluid intake, restoration of the impaired baroreceptor reflexes was brought about by ICV SQ treatment. These results indicate that the brain RAS strongly influences the regulation of blood pressure in DOCA-salt hypertensive rats and that its mechanism of action is closely related to changes in sodium excretion, vasopressin, and the baroreceptor reflexes.

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