Dataset Information

Serelaxin improves cardiac and renal function in DOCA-salt hypertensive rats.

ABSTRACT: Serelaxin, a recombinant form of the naturally occurring peptide hormone relaxin-2, is a pleiotropic vasodilating hormone that has been studied in patients with acute heart failure. In this study, the effects of serelaxin on cardiac and renal function, fibrosis, inflammation and lipid accumulation were studied in DOCA-salt treated rats. Uninephrectomized rats were assigned to two groups: controls provided with normal drinking water and DOCA provided with DOCA pellets and sodium chloride drinking water. After 4 weeks, the DOCA-salt rats were randomly selected and implanted with osmotic minipumps delivering vehicle or serelaxin for another 4 weeks. Treatment with serelaxin prevented cardiac and renal dysfunction in DOCA-salt rats. Serelaxin prevented cardiac and renal fibrosis, as determined by Picrosirius Red staining and Second Harmonic Generation (SHG) Microscopy. Treatment of DOCA-salt rats with serelaxin decreased renal inflammation, including the expression of TGF-?, NF?B, MCP-1, IL-1, IL-6, ICAM-1, VCAM-1 and CD68 macrophages. Serelaxin also decreased lipid accumulation in kidney in part by decreasing SREBP-1c, SREBP-2, ChREBP, FATP1, HMGCoAR, and LDL receptor, and increasing Acox1 and ABCA1. In summary, serelaxin reversed DOCA-salt induced cardiac and renal dysfunction.

SUBMITTER: Wang D

PROVIDER: S-EPMC5574886 | biostudies-other | 2017 Aug

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Serelaxin improves cardiac and renal function in DOCA-salt hypertensive rats.

Wang Dong D Luo Yuhuan Y Myakala Komuraiah K Orlicky David J DJ Dobrinskikh Evgenia E Wang Xiaoxin X Levi Moshe M

Scientific reports 20170829 1

Serelaxin, a recombinant form of the naturally occurring peptide hormone relaxin-2, is a pleiotropic vasodilating hormone that has been studied in patients with acute heart failure. In this study, the effects of serelaxin on cardiac and renal function, fibrosis, inflammation and lipid accumulation were studied in DOCA-salt treated rats. Uninephrectomized rats were assigned to two groups: controls provided with normal drinking water and DOCA provided with DOCA pellets and sodium chloride drinking ...[more]

PMID: 28851937

Similar Datasets

Project description:BackgroundDa-Chuan-Xiong Decoction (DCXD) is an aqueous extract from a classic Chinese herbal formula composed of dried rhizomes of Ligusticum chuanxiong Hort and Gastrodia elata Bl. in the mass ratio of 4 : 1. It has been long used to treat chronic cardiovascular disease caused by blood stasis and wind pathogen in the clinic. This experimental study aimed to investigate the blood pressure (BP)-lowering effect of DCXD treatment on hypertension and underlying mechanisms.MethodsMale Sprague-Dawley rats were used in the experiment, and the hypertensive models were created by administering deoxycorticosterone acetate (DOCA) in conjunction with a high salt intake in uninephrectomized rats. DCXD was administered to hypertensive rats by oral gavage daily at a dose of 5 g/kg or 2.5 g/kg bodyweight for 28 days. The brain sodium sensitivity, ENaC function, superoxide anion level, NADPH oxidase activity, and expression of ENaC, p67phox, p47phox, and Rac1 in the paraventricular nucleus were assessed by using the appropriate methods.ResultsThe 28 days of DCXD (5 g/kg) treatment significantly reduced the increased BP effectively, inhibited the enhanced heart index, kidney index, and 24 h urinary protein, and improved the progressive pathological changes of heart and kidney, which was comparable to that of the positive control amlodipine. DCXD treatment also caused a marked reduction in plasma norepinephrine and induced a significant improvement in brain sodium sensitivity and ENaC function in DOCA-salt hypertensive rats. Rats in DCXD-treated groups also exhibited decreased superoxide anion levels and NADPH oxidase activity in the paraventricular nucleus. The level of ENaC, p67phox, and Rac1 protein expression in the paraventricular nucleus was significantly downregulated by DCXD treatment in DOCA-salt hypertensive rats.ConclusionsThese findings indicate that the depressor action and sympathetic inhibition of DCXD on salt-sensitive hypertension may be by ameliorating brain sodium sensitivity, modulating ENaC function, and inhibiting the expression of ENaC and NADPH oxidase in the hypothalamic paraventricular nucleus.

Project description:1. The roles of nitric oxide (NO), superoxide anion (O(2)(-)), and hydrogen peroxide (H(2)O(2)) in the modulation of spontaneous tone were investigated in isolated aorta from deoxycorticosterone acetate (DOCA)-salt hypertensive rats. 2. Increases in preload from 1 to 5 g were accompanied by increases in spontaneous tone in aortic rings from DOCA-salt hypertensive rats but not from SHAM-normotensive rats. 3. Tone was higher in endothelium-denuded aortic rings than in endothelium-intact vessels. Inhibition of nitric oxide synthase (NOS) with 300 microM N(G)-nitro-L-arginine methyl ester (l-NAME) increased spontaneous tone. 4. Basal O(2)(-) generation was higher in aortic rings from DOCA-salt hypertensive rats than in those from SHAM-normotensive rats. Stretch increased O(2)(-) levels even further in the DOCA-salt group. In rings isolated from DOCA-salt hypertensive rats, administration of the O(2)(-) scavenger, superoxide dismutase (SOD, 150 U ml(-1)), or the nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase inhibitor, apocynin (100 microM), completely abolished the development of spontaneous tone in endothelium-intact aortic rings but not in endothelium-denuded or in L-NAME-treated rings. SOD and apocynin decreased the generation of O(2)(-) in endothelium-intact, endothelium-denuded, and L-NAME-treated aortic rings. 5. Oral treatment of DOCA-salt hypertensive rats with the O(2)(-) scavengers, tempol or tiron, or with apocynin for 3 weeks prevented the development of hypertension and abolished the increases in O(2)(-) generation and spontaneous tone. 6. Administration of catalase (1000 U ml(-1)) to aortic rings increased spontaneous tone in vessels from DOCA-salt hypertensive rats. 7. Administration of the cyclooxygenase (COX) inhibitor, valeroyl salicylate, or the thromboxane/prostaglandin antagonist, SQ 29548, to aortic rings abolished tone. 8. The results suggest that NO plays a major role in preventing the generation of spontaneous tone in isolated aortic rings from DOCA-salt hypertensive rats. NADPH-oxidase-derived O(2)(-) enhanced spontaneous tone by inactivating NO. Endogenous H(2)O(2) appears to mitigate the increase in tone. In addition, a COX component may also contribute to spontaneous tone.

Dataset Information

Serelaxin improves cardiac and renal function in DOCA-salt hypertensive rats.

Publications

Serelaxin improves cardiac and renal function in DOCA-salt hypertensive rats.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets