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Chronic ingestion of H1-antihistamines increase progression of atherosclerosis in apolipoprotein E-/- mice.

ABSTRACT: Although increased serum histamine levels and H1R expression in the plaque are seen in atherosclerosis, it is not known whether H1R activation is a causative factor in the development of the disease, or is a host defense response to atherogenic signals. In order to elucidate how pharmacological inhibition of histamine receptor 1 (H1R) signaling affects atherogenesis, we administered either cetirizine (1 and 4 mg/kg. b.w) or fexofenadine (10 and 40 mg/kg. b.w) to ApoE-/- mice maintained on a high fat diet for three months. Mice ingesting a low dose of cetirizine or fexofenadine had significantly higher plaque coverage in the aorta and cross-sectional lesion area at the aortic root. Surprisingly, the higher doses of cetirizine or fexofenadine did not enhance atherosclerotic lesion coverage over the controls. The low dose of fexofenadine, but not cetirizine, increased serum LDL cholesterol. Interestingly, the expression of iNOS and eNOS mRNA was increased in aortas of mice on high doses of cetirizine or fexofenadine. This may be a compensatory nitric oxide (NO)-mediated vasodilatory mechanism that accounts for the lack of increase in the progression of atherosclerosis. Although the administration of cetirizine did not alter blood pressure between the groups, there was a positive correlation between blood pressure and lesion/media ratio at the aortic root in mice receiving the low dose of cetirizine. However, this association was not observed in mice treated with the high dose of cetirizine or either doses of fexofenadine. The macrophages or T lymphocytes densities were not altered by low doses of H1-antihistamines, whereas, high doses decreased the number of macrophages but not T lymphocytes. The number of mast cells was decreased only in mice treated with low dose of fexofenadine. These results demonstrate that chronic ingestion of low therapeutic doses of cetirizine or fexofenadine enhance progression of atherosclerosis.

SUBMITTER: Raveendran VV

PROVIDER: S-EPMC4096593 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Chronic ingestion of H1-antihistamines increase progression of atherosclerosis in apolipoprotein E-/- mice.

Raveendran Vineesh V VV Smith Donald D DD Tan Xiaoyu X Sweeney Matthew E ME Reed Gregory A GA Flynn Colleen A CA Tawfik Ossama W OW Milne Ginger G Dileepan Kottarappat N KN

PloS one 20140714 7

Although increased serum histamine levels and H1R expression in the plaque are seen in atherosclerosis, it is not known whether H1R activation is a causative factor in the development of the disease, or is a host defense response to atherogenic signals. In order to elucidate how pharmacological inhibition of histamine receptor 1 (H1R) signaling affects atherogenesis, we administered either cetirizine (1 and 4 mg/kg. b.w) or fexofenadine (10 and 40 mg/kg. b.w) to ApoE-/- mice maintained on a high ...[more]

PMID: 25020133

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Project description:BackgroundNasal symptoms frequently coexist in patients with chronic cough, and non-sedating H1-receptor antihistamines (nsH1RAs) are often prescribed for cough management in several countries. However, recommendations on the use of nsH1RAs vary among chronic cough guidelines. This study aimed to examine the efficacy of nsH1RAs over placebos in adolescents or adults with chronic cough or allergic respiratory conditions that may present as chronic cough.MethodsElectronic databases were searched for studies published until November 2020. Randomized placebo-controlled trials of nsH1RAs reporting cough endpoints in adolescents or adults with chronic cough or cough-associated allergic respiratory conditions (allergic rhinitis, allergic asthma, or atopic cough) were included.ResultsA total of 10 placebo-controlled trials were identified. Three studies (one study each involving allergic rhinitis, allergic rhinitis with comorbid asthma, and atopic cough) described baseline and post-treatment cough scores, and all reported significant improvements in subjective cough scores; however, the magnitude of improvement was greater in the 2 studies of patients with atopic cough (relative improvement in cough frequency score: -36.6 ± 8.4%) or seasonal allergic rhinitis-associated cough (cough frequency score: -44.0 ± 7.3% and cough intensity score: -65.7 ± 8.3%) than in the 1 study of allergic rhinitis patients with comorbid asthma (-4.0 ± 1.3%). Meanwhile, the other 7 trials found conflicting results but lacked information on the baseline cough score and did not use validated cough measurement tools; thus, their clinical relevance could not be determined.ConclusionDespite the widespread use of nsH1RAs in patients with chronic cough, only a few clinical trials examining their benefits on cough outcomes have been conducted. There may be a subgroup of patients, particularly those with seasonal allergic rhinitis-associated cough or atopic cough, whose cough may improve with nsH1RA treatment. However, adequately powered trials with validated cough measurement tools are warranted to confirm the role of nsH1RAs in the management of patients with allergic phenotypes of chronic cough.

Project description:Electronic cigarettes (e-cigarettes), also known as electronic nicotine delivery systems, are a popular alternative to conventional nicotine cigarettes, both among smokers and those who have never smoked. In spite of the widespread use of e-cigarettes and the proposed detrimental cardiac and atherosclerotic effects of nicotine, the effects of e-cigarettes on these systems are not known. In this study, we investigated the cardiovascular and cardiac effects of e-cigarettes with and without nicotine in apolipoprotein-E knockout (ApoE-/-) mice. We developed an e-cigarette exposure model that delivers nicotine in a manner similar to that of human e-cigarettes users. Using commercially available e-cigarettes, bluCig PLUS, ApoE-/- mice were exposed to saline, e-cigarette without nicotine [e-cigarette (0%)], and e-cigarette with 2.4% nicotine [e-cigarette (2.4%)] aerosol for 12 wk. Echocardiographic data show that mice treated with e-cigarette (2.4%) had decreased left ventricular fractional shortening and ejection fraction compared with e-cigarette (0%) and saline. Ventricular transcriptomic analysis revealed changes in genes associated with metabolism, circadian rhythm, and inflammation in e-cigarette (2.4%)-treated ApoE-/- mice. Transmission electron microscopy revealed that cardiomyocytes of mice treated with e-cigarette (2.4%) exhibited ultrastructural abnormalities indicative of cardiomyopathy. Additionally, we observed increased oxidative stress and mitochondrial DNA mutations in mice treated with e-cigarette (2.4%). ApoE-/- mice on e-cigarette (2.4%) had also increased atherosclerotic lesions compared with saline aerosol-treated mice. These results demonstrate adverse effects of e-cigarettes on cardiac function in mice.NEW & NOTEWORTHY The present study is the first to show that mice exposed to nicotine electronic cigarettes (e-cigarettes) have decreased cardiac fractional shortening and ejection fraction in comparison with controls. RNA-seq analysis reveals a proinflammatory phenotype induced by e-cigarettes with nicotine. We also found increased atherosclerosis in the aortic root of mice treated with e-cigarettes with nicotine. Our results show that e-cigarettes with nicotine lead to detrimental effects on the heart that should serve as a warning to e-cigarette users and agencies that regulate them.

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Dataset Information

Chronic ingestion of H1-antihistamines increase progression of atherosclerosis in apolipoprotein E-/- mice.

Publications

Chronic ingestion of H1-antihistamines increase progression of atherosclerosis in apolipoprotein E-/- mice.

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