scholarly journals Oral administration of L-arginine decreases blood pressure and increases renal excretion of sodium and water in renovascular hypertensive rats

2003 ◽  
Vol 36 (7) ◽  
pp. 943-949 ◽  
Author(s):  
S.A. Gouvêa ◽  
M.R. Moysés ◽  
N.S. Bissoli ◽  
J.G.P. Pires ◽  
A.M. Cabral ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Oral Administration ◽  
Renal Excretion ◽  
Hypertensive Rats

P4481NI956/QGC006, a potent orally active, brain-penetrating aminopeptidase A inhibitor prodrug for treating hypertension

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Keck ◽  
H De Almeida ◽  
D Compere ◽  
N Inguimbert ◽  
A Flahault ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Oral Administration ◽  
Sulfonic Acid ◽  
Plasma Sodium ◽  
High Dose ◽  
Hypertensive Rats ◽  
Arterial Blood ◽  
Angiotensin Iii ◽  
Aminopeptidase A ◽  
Orally Active

Abstract Background Brain renin-angiotensin system hyperactivity has been implicated in the development and maintenance of hypertension. We previously showed that aminopeptidase A (APA) generates in the brain, angiotensin III, which exerts a tonic stimulatory control over blood pressure in hypertensive rats. Thus, the central injection of the specific and selective APA inhibitor, EC33 ((3S)-3-amino-4-sulfanyl-butane-1-sulfonic acid), by blocking the formation of brain angiotensin III, normalizes blood pressure in experimental models of hypertension. Therefore, brain APA appears as a potential new therapeutic target for the treatment of hypertension. We then developed RB150/firibastat, a prodrug of EC33, able of inhibiting brain APA activity and decreasing blood pressure in hypertensive rats after oral administration. Purpose However, considering the high dose of orally active RB150/firibastat required to decrease BP in spontaneously hypertensive rats (SHR) (150 mg/kg) and deoxycorticosterone acetate-salt (DOCA-salt) (50 mg/kg) rats, the aim of our work was to develop new more potent APA inhibitor prodrugs with greater bioavailability for inhibiting brain APA activity. Methods We used a salt- and volume-dependent model of hypertension, the DOCA-salt rat. For in vivo assessments of brain APA activity, brains were collected 4 hours after the oral administration. A catheter was inserted into the right femoral artery to monitor mean arterial blood pressure in alert rats. We evaluated plasma arginine-vasopressin (AVP) levels by radioimmunoassay. Rats were individually housed in metabolic cages for urine and electrolyte output measurements. Results We report here the development of a new APA inhibitor prodrug, NI956/QGC006, obtained by the disulfide bridge-mediated dimerization of NI929 ((3S,4S)-3-amino-4-mercapto-6-phenyl-hexane-1-sulfonic acid). NI929 is 10 more efficient than EC33 at inhibiting recombinant mouse APA activity in vitro. Following oral administration at a dose of 4 mg/kg in conscious DOCA-salt rats, NI956/QGC006 normalized brain APA activity and induced a marked decrease in blood pressure of −44±13 mmHg four hours after treatment (p<0.001), sustained over ten hours (−21±12 mmHg, p<0.05). Moreover, NI956/QGC006 decreased plasma AVP levels, and increased diuresis and natriuresis, that may decrease blood pressure by reducing the size of the fluid compartment. Finally, NI956/QGC006 did not affect plasma sodium and potassium concentrations. Conclusions This study shows that NI956/QGC006 is a “best-in-class” central-acting APA inhibitor prodrug, belonging to the same drug class as RB150/firibastat, supporting the strategy of brain APA inhibition for hypertension treatment. Acknowledgement/Funding ANR (Agence Nationale de la Recherche) grant to Catherine Llorens-Cortes (LabCom CARDIOBAPAI) and Quantum Genomics financial support.

scholarly journals Evidence that Nitric Oxide is Involved in the Blood Pressure Lowering Effect of the Peptide AVFQHNCQE in Spontaneously Hypertensive Rats

Nutrients ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 225 ◽  
Author(s):  
Anna Mas-Capdevila ◽  
Lisard Iglesias-Carres ◽  
Anna Arola-Arnal ◽  
Gerard Aragonès ◽  
Amaya Aleixandre ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Oral Administration ◽  
Spontaneously Hypertensive Rats ◽  
Protein Hydrolysate ◽  
Antioxidant Properties ◽  
Hypertensive Rats ◽  
Blood Pressure Lowering Effect ◽  
Spontaneously Hypertensive ◽  
Lowering Effect

AVFQHNCQE is an antihypertensive nonapeptide obtained from a chicken foot protein hydrolysate. The present study aims to investigate the mechanisms involved in its blood pressure (BP)-lowering effect. Male (17–20 weeks old) spontaneously hypertensive rats (SHR) were used in this study. Rats were divided into two groups and orally administered water or 10 mg/kg body weight (bw) AVFQHNCQE. One hour post-administration, animals of both groups were intra-peritoneally treated with 1 mL of saline or with 1 mL of saline containing 30 mg/kg bw Nω-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthesis, or with 1 mL of saline containing 5 mg/kg bw indomethacin, which is an inhibitor of prostacyclin synthesis (n = 6 per group). Systolic BP was recorded before oral administration and six hours after oral administration. In an additional experiment, SHR were administered water or 10 mg/kg bw AVFQHNCQE (n = 6 per group) and sacrificed six hours post-administration to study the mechanisms underlying the peptide anti-hypertensive effect. Moreover, the relaxation caused by AVFQHNCQE in isolated aortic rings from Sprague-Dawley rats was evaluated. The BP-lowering effect of the peptide was not changed after indomethacin administration but was completely abolished by L-NAME, which demonstrates that its anti-hypertensive effect is mediated by changes in endothelium-derived NO availability. In addition, AVFQHNCQE administration downregulated aortic gene expression of the vasoconstrictor factor endothelin-1 and the endothelial major free radical producer NADPH. Moreover, while no changes in plasma ACE activity were observed after its administration, liver GSH levels were higher in the peptide-treated group than in the water group, which demonstrates that AVFQHNCQE presents antioxidant properties.

Fermented rice bran extract improves blood pressure and glucose in stroke-prone spontaneously hypertensive rats

2019 ◽  
Vol 49 (5) ◽  
pp. 844-853 ◽  
Author(s):  
Ardiansyah ◽  
Wahyudi David ◽  
Dody Dwi Handoko ◽  
Bram Kusbiantoro ◽  
Slamet Budijanto ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Oral Administration ◽  
Rice Bran ◽  
Spontaneously Hypertensive Rats ◽  
Radical Scavenging ◽  
Total Phenolic ◽  
Hypertensive Rats ◽  
Content Type ◽  
Spontaneously Hypertensive

PurposeThe purpose of this study was to evaluate thein vitroandin vivoeffects of three varieties of Indonesian fermented rice bran (RB) (Inpari 6, Inpari 30 and Inpara 1).Design/methodology/approachThree types of RB were fermented usingRhizopus oligosporus. The total phenolic content (TPC) was determined using the Folin–Ciocalteau method, and antioxidant activity was analyzed by measuring the 2,2-diphenyl-1-picrylhydrazyl free radical scavenging activity (RSA). Forin vivoanalyses, one week after acclimatization, stroke-prone spontaneously hypertensive rats (n= 4, 12 weeks of age) were divided into two groups and orally administered fermented RB (40 mg/kg body weight) or distilled water as a control after 16 h of fasting. Blood pressure (BP) was measured before and 2, 4 and 6 h after administration with a BP monitor without warming. Six days later, the rats were subject to the same procedure and sacrificed after 6 h of oral administration. Blood was collected and the plasma was separated to measure nitric oxide, glucose and insulin levels.FindingsThe highest TPC and RSA of fermented RB were obtained from Inpari 30 after incubation for 72 h (260.33 ± 0.39 mg GAE/100 g dry basis and 83.71 ± 0.61 per cent), respectively. Furthermore, single oral administration of fermented RB improved BP (p< 0.05) and glucose metabolism after 6 h of administration (p< 0.05).Originality/valueThis is the first study to evaluate the effects of fermented RB on improving high BP and glucose profiles by using a spontaneously hypertensive animal model.

Antibiotics attenuate experimental hypertension in rats

1985 ◽  
Vol 105 (3) ◽  
pp. 347-350 ◽  
Author(s):  
J. W. Honour ◽  
S. P. Borriello ◽  
U. Ganten ◽  
P. Honour
Keyword(s):  
Blood Pressure ◽  
Oral Administration ◽  
High Blood Pressure ◽  
Spontaneously Hypertensive Rats ◽  
Experimental Hypertension ◽  
Sprague Dawley ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Intramuscular Injections ◽  
Sprague Dawley Rats

ABSTRACT Hypertension was produced in Sprague–Dawley rats by intramuscular injections of either corticosterone or ACTH. Lower increases in blood pressure to these challenges were observed in Sprague–Dawley rats pretreated with neomycin or vancomycin which alone had no effect on blood pressure or growth. The development of high blood pressure in spontaneously hypertensive rats of a stroke-prone substrain was also attenuated by oral administration of neomycin. These results suggest that experimental hypertension can be modulated by the administration of antibiotics. J. Endocr. (1985) 105, 347–350

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