Influence of sex on cardiovascular drug responses: role of estrogen

Abdel‐Rahman, Abdel A.

doi:10.1016/j.coph.2017.02.002

Cited by 12 publications

(9 citation statements)

References 42 publications

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“…Despite the increased HR, we did not identify changes in MAP of female controls. It has been extensively explained in studies that an estrogen protective effect upon MAP occurs due to its actions in the kidney (e.g., females have higher levels of the vasodilator angiotensin compared to males) (Bhatia et al., ; Brosnihan et al., ; Brown et al., ; Shenoy et al., ; Xue et al., ) and on nitric oxide (NO) production in the heart and vasculature (Abdel‐rahman, ; Caulin‐Glaser et al., ; Chen et al., ; El‐Mas and Abdel‐Rahman, ; Mendelsohn and Karas, ; Wang and Abdel‐Rahman, ). It has also been proposed that although female rats show an increase in HR, the MAP would not be altered because of the sex differences in control of baroreflex responses by the nucleus of the solitary tract (NTS), nucleus ambiguous (NA), parabrachial nucleus (PBN), and caudal and rostral ventrolateral medulla (Abdel‐rahman, ; Mohamed et al., ; Wyss and Carlson, ; Xue et al., ).…”

Section: Discussionmentioning

confidence: 99%

Prolonged Exposure to Alcohol Vapor Causes Change in Cardiovascular Function in Female but not in Male Rats

Costa-Ferreira

Engi

et al. 2019

Alcoholism Clin & Exp Res

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Background: Alcohol abuse is a health concern worldwide. Studies have associated alcohol abuse with cardiovascular impairments. In this study, we investigated differences in the effects of chronic alcohol vapor exposure on cardiovascular function between male and female rats by using the alcohol vapor chamber method to induce alcohol addiction-like behaviors in rats.Methods: We exposed male and female Long-Evans rats to alcohol vapor for 14 hours, followed by ethanol withdrawal for 10 hours, for 30 consecutive days or room air (control groups). The animals underwent preparation for the surgical implantation of cannulas into femoral vessels, for allowing the assessment of the basal arterial pressure and heart rate values, baroreflex function, and autonomic activity.Results: Female control rats showed higher basal heart rate compared to male control rats. Chronic alcohol vapor inhalation reduced basal heart rate in females, but not in males; this effect was followed by an increase in the parasympathetic tone of the heart. Further, female rats subjected to alcohol vapor showed an increase in the baroreflex activity.Conclusions: These findings suggest that females are more sensitive to chronic alcohol vapor exposure than males because they had a reduction in basal heart rate and changes in the baroreflex activity.

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Section: Discussionmentioning

confidence: 99%

Prolonged Exposure to Alcohol Vapor Causes Change in Cardiovascular Function in Female but not in Male Rats

Costa-Ferreira

Engi

et al. 2019

Alcoholism Clin & Exp Res

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“…The anticoagulant drug lepirudin is excreted by the kidney with systemic clearance in women about 25% lower than in men (NDA 020807 [31]). But PK variables do not translate linearly into phenotypes; thus, in women lepirudin is detectible in the circulation for up to 48 h, compared to just 2 h in men, which greatly increases the potential for undesired bleeding [32]; indeed, in this example, low molecular weight heparin-induced thrombocytopenia is a clinically important ADR which occurs more frequently in women than men [33], a difference that corresponded to much higher drug exposure as indicated by female-bias in multiple PK measures.…”

Section: Reasons Why Men and Women Respond Differently To Drugsmentioning

confidence: 99%

Sex differences in pharmacokinetics predict adverse drug reactions in women

2020

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Background: Women experience adverse drug reactions, ADRs, nearly twice as often as men, yet the role of sex as a biological factor in the generation of ADRs is poorly understood. Most drugs currently in use were approved based on clinical trials conducted on men, so women may be overmedicated. We determined whether sex differences in drug pharmacokinetics, PKs, predict sex differences in ADRs. Methods: Searches of the ISI Web of Science and PubMed databases were conducted with combinations of the terms: drugs, sex or gender, pharmacokinetics, pharmacodynamics, drug safety, drug dose, and adverse drug reaction, which yielded over 5000 articles with considerable overlap. We obtained information from each relevant article on significant sex differences in PK measures, predominantly area under the curve, peak/maximum concentrations, and clearance/elimination rates. ADRs were identified from every relevant article and recorded categorically as female-biased, male-biased, or not sex-biased. Results: For most of the FDA-approved drugs examined, elevated blood concentrations and longer elimination times were manifested by women, and these PKs were strongly linked to sex differences in ADRs. Of the 86 drugs evaluated, 76 had higher PK values in women; for 59 drugs with clinically identifiable ADRs, sex-biased PKs predicted the direction of sex-biased ADRs in 88% of cases. Ninety-six percent of drugs with female-biased PK values were associated with a higher incidence of ADRs in women than men, but only 29% of male-biased PKs predicted male-biased ADRs. Accessible PK information is available for only a small fraction of all drugs Conclusions: Sex differences in pharmacokinetics strongly predict sex-specific ADRs for women but not men. This sex difference was not explained by sex differences in body weight. The absence of sex-stratified PK information in public records for hundreds of drugs raises the concern that sex differences in PK values are widespread and of clinical significance. The common practice of prescribing equal drug doses to women and men neglects sex differences in pharmacokinetics and dimorphisms in body weight, risks overmedication of women, and contributes to female-biased adverse drug reactions. We recommend evidence-based dose reductions for women to counteract this sex bias.

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“…Despite the fact that females are known to have specific cardiovascular characteristics, the treatments that are specifically directed toward this gender are nonexistent [27]. Additionally, there is a dearth of animal models of atherosclerotic disease for this genus.…”

Section: Discussionmentioning

confidence: 99%

Development of a Predictive Model to Induce Atherogenesis and Hepato-Renal Impairment in Female Rats

et al. 2019

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Therapeutic approaches for the treatment of dyslipidemia and atherosclerosis have radically changed in recent decades. Part of this advance undeniably stems from basic biomedical research that has provided a better understanding and identification of new therapeutic targets. The aim of this work was to develop a model to induce atherogenesis and hepato-renal impairment in female Wistar rats. The following groups received the respective treatments for 60 days: control animals, non-ovariectomized rats that received an atherogenic diet (NEAD), ovariectomized rats that received an atherogenic diet (NOAD), non-ovariectomized rats that received an atherogenic diet and oral Nω-nitro-l-arginine methyl ester hydrochloride (l-NAME; LEAD), and ovariectomized rats that received an atherogenic diet and oral l-NAME (LOAD). Animals in the NEAD, NOAD, LEAD, and LOAD groups also received methimazole and cholecalciferol daily. Urinary, biochemical, hemodynamic, and electrocardiographic parameters and renal function were assessed. Samples of the liver, heart, kidney, and arteries were collected to investigate redox status and perform histopathological analyses. All of the groups developed dyslipidemia and hepatic steatosis. Only the NEAD group developed arterial lesions that were compatible with fatty streaks. Renal function was significantly impaired in the LEAD and NOAD groups. These results indicate a viable alternative to induce atherogenesis and hepato-renal impairment in female rats.

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Influence of sex on cardiovascular drug responses: role of estrogen

Cited by 12 publications

References 42 publications

Prolonged Exposure to Alcohol Vapor Causes Change in Cardiovascular Function in Female but not in Male Rats

Prolonged Exposure to Alcohol Vapor Causes Change in Cardiovascular Function in Female but not in Male Rats

Sex differences in pharmacokinetics predict adverse drug reactions in women

Development of a Predictive Model to Induce Atherogenesis and Hepato-Renal Impairment in Female Rats

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