Losartan does not inhibit cigarette smoke-induced lung inflammation in mice

Hepworth, M. L.; Passey, Samantha; Seow, Huei Jiunn; Vlahos, Ross

doi:10.1038/s41598-019-51504-2

Cited by 8 publications

(6 citation statements)

References 64 publications

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“…The lack of differences in food intake, urine output and creatinine clearance between control and losartan-treated rats observed in the current study are also in line with results of previous studies [17][18][19][20][21][22]. Interestingly, we did not observe any differences in serum concentrations and urinary excretions of the electrolytes, albumin and protein between controls and losartan-treated rats (Tables 2 and 3), in both groups.…”

Section: Discussionsupporting

confidence: 93%

Changes in the Urinary Metabolites in Losartan-Treated Spontaneously Hypertensive Rats

Azis¹,

Kamal²,

Radjeni³

et al. 2021

JCHS

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Introduction: This study examined the association of losartan induced changes in urinary metabolomic profile with the changes in blood pressure (BP) and renin-angiotensin- aldosterone system (RAAS) in spontaneously hypertensive rats (SHR). Methods: Male SHR were administered with either 0.5 mL of distilled water (control group, n=6) or 10 mg.kg -1 of losartan (group 2, n=6) daily by oral gavage for 4 weeks. Body weight, BP, food and water intake were measured weekly. At week 4, urine was collected for urinary electrolyte analysis and metabolite profiling, after which the animals were euthanised by decapitation and blood was collected for analysis of components of RAAS and electrolyte concentrations. Urine metabolite profile of SHR was determined using proton nuclear magnetic resonance ( 1 H-NMR) spectrometry combined with multivariate data analysis. Results: At week 4, losartan- treated SHR had significantly lower BP than non-treated SHR. There were no differences in water and food intake, body weight, serum and urinary electrolyte concentrations or in their urinary excretions between the two groups. No differences were evident in the components of RAAS except that the angiotensinogen level was significantly higher in losartan-treated SHR compared to non-treated SHR. Orthogonal partial least squares discriminant analysis (OPLS-DA) showed clear separation of urinary metabolites between control and losartan-treated SHR. Losartan-treated SHR group was separated from the control group by changes in the intermediates involved in glycine, serine and threonine metabolism. Conclusion: Antihypertensive effect of losartan in SHR seems to be associated with changes in urinary metabolite profile, particularly involving the metabolism of glycine, serine and threonine.

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Section: Discussionsupporting

confidence: 93%

Changes in the Urinary Metabolites in Losartan-Treated Spontaneously Hypertensive Rats

Azis¹,

Kamal²,

Radjeni³

et al. 2021

JCHS

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“…At the end of the study, the lungs were lavaged in situ using phosphate buffered saline (PBS) as previously published [ 7 , 32 , 34 ]. Bronchoalveolar lavage fluid (BALF) cytospin slides were prepared and analysed; identifying macrophages, neutrophils and lymphocytes using standard morphological criteria.…”

Section: Methodsmentioning

confidence: 99%

Ebselen prevents cigarette smoke-induced cognitive dysfunction in mice by preserving hippocampal synaptophysin expression

Luca

Brassington

Chan

et al. 2022

J Neuroinflammation

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Background Cigarette smoking (CS) is the leading cause of chronic obstructive pulmonary disease (COPD). The “spill-over” of pulmonary inflammation into the systemic circulation may damage the brain, leading to cognitive dysfunction. Cessation of CS can improve pulmonary and neurocognitive outcomes, however, its benefit on the neuroinflammatory profile remains uncertain. Here, we investigate how CS exposure impairs neurocognition and whether this can be reversed with CS cessation or an antioxidant treatment. Methods Male BALB/c mice were exposed to CS (9 cigarettes/day for 8 weeks) followed by 4 weeks of CS cessation. Another cohort of CS-exposed mice were co-administrated with a glutathione peroxidase mimetic, ebselen (10 mg/kg) or vehicle (5% CM-cellulose). We assessed pulmonary inflammation, spatial and working memory, and the hippocampal microglial, oxidative and synaptic profiles. Results CS exposure increased lung inflammation which was reduced following CS cessation. CS caused spatial and working memory impairments which were attributed to hippocampal microglial activation and suppression of synaptophysin. CS cessation did not improve memory deficits or alter microglial activation. Ebselen completely prevented the CS-induced working and spatial memory impairments, which was associated with restored synaptophysin expression without altering microglial activation. Conclusion We were able to model the CS-induced memory impairment and microglial activation seen in human COPD. The preventative effects of ebselen on memory impairment is likely to be dependent on a preserved synaptogenic profile. Cessation alone also appears to be insufficient in correcting the memory impairment, suggesting the importance of incorporating antioxidant therapy to help maximising the benefit of cessation.

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“…When administered to smokers, losartan normalized the smoking-increased levels of IL-6 [95]. Macrophages co-cultured with losartan poorly produced IL-1beta, but this drug failed to reduce IL-1beta mRNA expression [96].…”

Section: Valsartan Losartanmentioning

confidence: 99%

Immunomodulatory Activity of the Most Commonly Used Antihypertensive Drugs—Angiotensin Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers

Bryniarski

Nazimek

Marcinkiewicz

2022

IJMS

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This review article is focused on antihypertensive drugs, namely angiotensin converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB), and their immunomodulatory properties reported in hypertensive patients as well as in experimental settings involving studies on animal models and cell lines. The immune regulatory action of ACEI and ARB is mainly connected with the inhibition of proinflammatory cytokine secretion, diminished expression of adhesion molecules, and normalization of CRP concentration in the blood plasma. The topic has significant importance in future medical practice in the therapy of patients with comorbidities with underlying chronic inflammatory responses. Thus, this additional effect of immune regulatory action of ACEI and ARB may also benefit the treatment of patients with metabolic syndrome, allergies, or autoimmune disorders.

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Losartan does not inhibit cigarette smoke-induced lung inflammation in mice

Cited by 8 publications

References 64 publications

Changes in the Urinary Metabolites in Losartan-Treated Spontaneously Hypertensive Rats

Changes in the Urinary Metabolites in Losartan-Treated Spontaneously Hypertensive Rats

Ebselen prevents cigarette smoke-induced cognitive dysfunction in mice by preserving hippocampal synaptophysin expression

Immunomodulatory Activity of the Most Commonly Used Antihypertensive Drugs—Angiotensin Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers

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