scholarly journals Chronic immunoneutralization of brain angiotensin-(1-12) lowers blood pressure in transgenic (mRen2)27 hypertensive rats

2009 ◽  
Vol 297 (1) ◽  
pp. R111-R115 ◽  
Author(s):  
Katsunori Isa ◽  
Maria Antonia García-Espinosa ◽  
Amy C. Arnold ◽  
Nancy T. Pirro ◽  
Ellen N. Tommasi ◽  
...  

Angiotensin-(1-12) [ANG-(1-12)] is a newly identified peptide detected in a variety of rat tissues, including the brain. To determine whether brain ANG-(1-12) participates in blood pressure regulation, we treated male adult (mRen2)27 hypertensive rats (24–28 wk of age) with Anti-ANG-(1-12) IgG or Preimmune IgG via an intracerebroventricular cannula for 14 days. Immunoneutralization of brain ANG-(1-12) lowered systolic blood pressure (−43 ± 8 mmHg on day 3 and −26 ± 7 mmHg on day 10 from baseline, P < 0.05). Water intake was lower on intracereroventricular day 6 in the Anti-ANG-(1-12) IgG group, accompanied by higher plasma osmolality on day 13, but there were no differences in urine volume, food intake, or body weight during the 2-wk treatment. In Preimmune IgG-treated animals, there were no significant changes in these variables over the 2-wk period. The antihypertensive effects produced by endogenous neutralization of brain ANG-(1-12) suggest that ANG-(1-12) is functionally active in brain pathways regulating blood pressure.

1982 ◽  
Vol 242 (4) ◽  
pp. H496-H499 ◽  
Author(s):  
W. Rascher ◽  
R. E. Lang ◽  
T. Unger ◽  
D. Ganten ◽  
F. Gross

In stroke-prone spontaneously hypertensive rats (SHRSP) and in normotensive Wistar-Kyoto rats (WKY), arginine vasopressin (AVP) was measured by means of a radioimmunoassay in the plasma, the pituitary gland, the hypothalamus, and the brain stem. In 6- and 14-wk-old SHRSP, the plasma concentration of AVP was lower than in age-matched WKY (P less than 0.01), whereas it was elevated at 28 wk of age (P less than 0.01). In the pituitary of 6-wk-old SHRSP, AVP was higher than in WKY (P less than 0.05), but no such difference was found in older rats. In the hypothalamus and the brain stem, AVP content was reduced in all age groups of SHRSP. Plasma osmolality was diminished in 28-wk-old SHRSP only (P less than 0.01), whereas hematocrit in all age groups was higher in SHRSP than in WKY. It is concluded that the secretion of AVP and possibly its synthesis in the hypothalamus are reduced in SHRSP. Whether the reduced AVP content in the brain stem is related to the sustained elevation of blood pressure has to be studied further.


1978 ◽  
Vol 234 (5) ◽  
pp. H629-H637 ◽  
Author(s):  
J. F. Mann ◽  
M. I. Phillips ◽  
R. Dietz ◽  
H. Haebara ◽  
D. Ganten

The angiotensin II (AII) antagonist [Sar1-Ala8]AII (Saralasin) was injected into the brain ventricles (IVT) and intravenously (IV) in five different types of hypertensive unanesthetized rats. Renal hypertension was studied 16-22 days after kidney clipping. Intravenous infusions of cumulative doses (0.1-100 microgram/kg per min) and IVT injections (5-40 microgram) of Saralasin did not change mean arterial pressure (MAP) in controls and in one-clip, one-kidney Goldblatt hypertension, whereas MAP decreased in one-clip, two-kidney Goldblatt hypertension following IV and IVT Saralasin. In two-clip, two kidney hypertensive rats, IVT Saralasin decreased MAP but was ineffective when infused IV. Both IV and IVT Saralasin increased MAP in DOC hypertension. In spontaneously hypertensive (SH) rats, IV Saralasin increased MAP; IVT injection decreased MAP. The effect of IVT Saralasin in SH rats persisted 15-20 h after nephrectomy. We conclude that plasma AII may contribute to peripheral and central mechanisms of blood pressure regulation. The dissociation of the effects of IV and IVT Saralasin and the persistance of blood pressure decrease in nephrectomized SH rats following IVT Saralasin further support a role for locally formed brain angiotensin.


Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Gertrude Arthur ◽  
Audrey Poupeau ◽  
Kellea Nichols ◽  
Jacqueline Leachman ◽  
Analia S Loria ◽  
...  

Recent studies showed that soluble prorenin receptor (sPRR) plays an important role in blood pressure regulation and in water balance. In rodent models, sPRR contributes to AngII production by increasing renin activity, systolic blood pressure (SBP) and aquaporin2 (AQP2)-dependent antidiuretic action. However, there is a gap of knowledge concerning the functional role of locally produced sPRR from the kidney. Therefore, we evaluated the kidney-derived human sPRR role in SBP control and fluid homeostasis. Human sPRR-Myc-tag transgenic mice were bred with mice expressing Hoxb7/Cre to selectively express human sPRR in the collecting duct (RHsPRR). RHsPRR and control (CTL) male mice were fed a standard diet for 10 months (n=8-11/group). Body weight and urine volume were examined and SBP measured by radiotelemetry. Western blot analysis depicted the presence of human sPRR-Myc-tag (28 KDa) in the cortex and medulla of RHsPRR male mice validating the humanized mouse model. Body weight did not change and 24hr-SBP was similar between CLT and RHsPRR mice (128±2 and 122±5 mmHg, respectively). However, the chronic response to losartan treatment was reduced in RHsPRR compared to CTL (ΔSBP: CTL: -9±3; RHsPRR: -5±1 mmHg, P<0.05). Kidney-derived human sPRR did not change GFR (838±75 vs 1088±163 μl/min/100g BW) and urinary vasopressin (0.62±0.21; 0.72±0.20 ng/mg creatinine), while modestly decreasing urine excretion rate by ~40% (CTL: 1.04±0.20; RHsPRR: 0.57±0.25 ml/day). Furthermore, RHsPRR mice had higher AQP2 protein expression in renal cortex (CTL: 0.24±0.07; RHsPRR: 4.11±0.70 AU, P<0.05) and medulla (CTL: 0.11±0.04; RHsPRR: 4.03±1.74 AU, P<0.05) than CTL mice. Kidney-derived human sPRR significantly increased phosphorylation of ERK 1/2 in the cortex compared to CTL (CTL: 5.4±1.0; RHsPRR: 9.2±1.4 AU, P<0.05), an MAPK involved in the regulation of water balance. In addition, RHsPRR mice showed increased plasma osmolality compared to CTL mice (CTL: 349±2; RHsPRR: 357±2 mOsm/kg, P<0.05). Overall, our data suggest that renal human sPRR could contribute to the increase in plasma tonicity by promoting the activation of ERK1/2-AQP2 pathway. Whether this signaling is associated with impaired antihypertensive effects of AT1R blockage remains under investigation.


1987 ◽  
Vol 72 (3) ◽  
pp. 321-327 ◽  
Author(s):  
A. Louise Sugden ◽  
Barbara L. Bean ◽  
James A. Straw

1. These studies were designed to investigate the effects of high dietary K+ on electrolyte and water balance in young spontaneously hypertensive rats (SHR) and to relate these effects to changes in blood pressure. 2. The high K+ diet reduced blood pressure by approximately 10 mmHg during the development of hypertension. Blood pressure, however, plateaued at the same maximum level as control by age 13 weeks. 3. Rats fed the high K+ diet showed a significant increase in water intake and urine volume throughout the treatment period but no change in plasma volume or extracellular fluid volume occurred. 4. A slight natriuresis was also observed in rats on the high K+ diet, but this was not of sufficient magnitude to decrease total body Na+. 5. These results confirm previous findings that K+ causes a diuresis and a natriuresis, but demonstrate that the diuretic action of K+ cannot explain its antihypertensive properties in young SHR.


Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Takuto Nakamura ◽  
Masanobu Yamazato ◽  
Akio Ishida ◽  
Yusuke Ohya

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.


1983 ◽  
Vol 245 (5) ◽  
pp. F615-F621 ◽  
Author(s):  
R. L. Woods ◽  
C. I. Johnston

Normal Long-Evans rats, when dehydrated for up to 72 h, have a progressive rise in plasma vasopressin that is associated with a fall in body weight and urine volume, a rise in plasma and urine osmolality, and the maintenance of normal systolic blood pressure. In contrast, Brattleboro diabetes insipidus rats, genetically deficient in vasopressin, when dehydrated to achieve an equivalent body weight loss, have a significant 15 mmHg fall in systolic blood pressure. Even when fluid balance is corrected in the Brattleboro rats by the continuous administration of 1-desamino-8-D-arginine vasopressin, a synthetic vasopressin analogue with potent antidiuretic properties but minimal pressor activity, blood pressure still falls when the animals are dehydrated. In contrast, Brattleboro rats infused with exogenous arginine vasopressin to produce a plasma vasopressin level of 18.9 +/- 3.5 pg X ml-1 are able to maintain normal blood pressure during 48 h of dehydration. This level of vasopressin is comparable to the level found endogenously in dehydrated Long-Evans rats and is nonpressor in normal rats. These results suggest that both the antidiuretic and vasoconstrictor properties of vasopressin are important in the cardiovascular response to dehydration.


Endocrinology ◽  
2007 ◽  
Vol 148 (4) ◽  
pp. 1638-1647 ◽  
Author(s):  
Hirofumi Hashimoto ◽  
Hiroaki Fujihara ◽  
Makoto Kawasaki ◽  
Takeshi Saito ◽  
Minori Shibata ◽  
...  

Ghrelin is known as a potent orexigenic hormone through its action on the brain. In this study, we examined the effects of intracerebroventricular (icv) and iv injection of ghrelin on water intake, food intake, and urine volume in rats deprived of water for 24 h. Water intake that occurred after water deprivation was significantly inhibited by icv injection of ghrelin (0.1, 1, and 10 nmol/rat) in a dose-related manner, although food intake was stimulated by the hormone. The antidipsogenic effect was as potent as the orexigenic effect. Similarly, water intake was inhibited, whereas food intake was stimulated dose dependently after iv injection of ghrelin (0.1, 1, and 10 nmol/kg). The inhibition of drinking was comparable with, or even more potent than, atrial natriuretic peptide (ANP), an established antidipsogenic hormone, when administered icv, although the antidipsogenic effect lasted longer. ANP had no effect on food intake. Urine volume decreased dose relatedly after icv injection of ghrelin but not by ANP. Intravenous injection of ghrelin had no effect on urine volume. Because drinking usually occurs with feeding, food was withdrawn to remove the prandial drinking. Then the antidipsogenic effect of ghrelin became more potent than that of ANP and continued longer than when food was available. Expression of Fos was increased in the area postrema and the nucleus of the tractus solitarius by using immunohistochemistry after icv and iv injection of ghrelin. The present study convincingly showed that ghrelin is a potent antidisogenic peptide in rats.


Endocrinology ◽  
2019 ◽  
Vol 160 (10) ◽  
pp. 2441-2452 ◽  
Author(s):  
Tomokazu Hata ◽  
Noriyuki Miyata ◽  
Shu Takakura ◽  
Kazufumi Yoshihara ◽  
Yasunari Asano ◽  
...  

Abstract Anorexia nervosa (AN) results in gut dysbiosis, but whether the dysbiosis contributes to AN-specific pathologies such as poor weight gain and neuropsychiatric abnormalities remains unclear. To address this, germ-free mice were reconstituted with the microbiota of four patients with restricting-type AN (gAN mice) and four healthy control individuals (gHC mice). The effects of gut microbes on weight gain and behavioral characteristics were examined. Fecal microbial profiles in recipient gnotobiotic mice were clustered with those of the human donors. Compared with gHC mice, gAN mice showed a decrease in body weight gain, concomitant with reduced food intake. Food efficiency ratio (body weight gain/food intake) was also significantly lower in gAN mice than in gHC mice, suggesting that decreased appetite as well as the capacity to convert ingested food to unit of body substance may contribute to poor weight gain. Both anxiety-related behavior measured by open-field tests and compulsive behavior measured by a marble-burying test were increased only in gAN mice but not in gHC mice. Serotonin levels in the brain stem of gAN mice were lower than those in the brain stem of gHC mice. Moreover, the genus Bacteroides showed the highest correlation with the number of buried marbles among all genera identified. Administration of Bacteroides vulgatus reversed compulsive behavior but failed to exert any substantial effect on body weight. Collectively, these results indicate that AN-specific dysbiosis may contribute to both poor weight gain and mental disorders in patients with AN.


Author(s):  
Siska Siska ◽  
Franciscus D. Suyatna ◽  
Abdul Mun'im ◽  
Anton Bahtiar

Based on previous reports, the combination of captopril and celery could reduce blood pressure in hypertensive patients. This study aimed to investigate the changes of blood pressure, urine volume, sodium, and potassium level, due to concomitant administration of captopril with celery extract orally in male rats induced by 4% NaCl. The blood pressure was measured using a non-invasive tail method. The urine and blood were collected, and the sodium, potassium concentration, and cumulative urine volume were measured. The combination of 5 mg/kgBW of captopril and 40 mg/kgBW of celery extract decreased the blood pressure in hypertensive rats better than 5 mg/kgBW of captopril alone. The fell in blood pressure was followed by an increase in urine volume. Urinary and serum sodium, serum potassium levels tended to increase in all treatment groups, but not significantly different from the healthy group. Urinary potassium levels tended to decrease except in the combined 5 mg/kgBW of captopril and 40 mg/kgBW of celery extract. In conclusion, oral administration of a combination of 5 mg/kgBW captopril and 40 mg/kgBW celery extract decreased the blood pressure to the standard value in NaCl-induced hypertension rats.Keywords: Apium graveolens, captopril, celery, hypertension, pharmacodynamic


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