Sex: A change in our guidelines to authors to ensure that this is no longer an ignored experimental variable

Docherty, James R.; Stanford, S Clare; Panattieri, Reynold A; Alexander, Steve P.H.; Cirino, Giuseppe; George, Christopher H.; Hoyer, Daniel; Izzo, Angelo A.; Ji, Yong; Lilley, Elliot; Sobey, Christopher G.; Stanley, Phil; Stefańska, Barbara; Stephens, Gary J.; Teixeira, Mauro Martins; Ahluwalia, Amrita

doi:10.1111/bph.14761

Cited by 60 publications

(64 citation statements)

References 31 publications

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“…This is not the case with non-diabetic subjects (Peters et al, 2014). However, with few exceptions, most of the studies in animal models have been conducted in males (Docherty et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Endothelial Dysfunction and Passive Changes in the Aorta and Coronary Arteries of Diabetic db/db Mice

Beck

Comerma-Steffensen

et al. 2020

Front. Physiol.

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Endothelial cell dysfunction and vessel stiffening are associated with a worsened prognosis in diabetic patients with cardiovascular diseases. The present study hypothesized that sex impacts endothelial dysfunction and structural changes in arteries from diabetic mice. In diabetic (db/db) and normoglycaemic (db/db+) mice, the mechanical properties were investigated in pressurized isolated left anterior descending coronary arteries and aorta segments that were subjected to tensile testing. Functional studies were performed on wire-mounted vascular segments. The male and female db/db mice were hyperglycaemic and had markedly increased body weight. In isolated aorta segments without the contribution of smooth muscle cells, load to rupture, viscoelasticity, and collagen content were decreased suggesting larger distensibility of the arterial wall in both male and female db/db mice. In male db/db aorta segments with smooth muscle cell contribution, lumen diameter was smaller and the passive stretch-tension curve was leftward-shifted, while they were unaltered in female db/db aorta segments versus control db/db+ mice. In contrast to female db/db mice, coronary arteries from male db/db mice had altered stress-strain relationships and increased distensibility. Transthoracic echocardiography revealed a dilated left ventricle with unaltered cardiac output, while aortic flow velocity was decreased in male db/db mice. Impairment of acetylcholine relaxation was aggravated in aorta from female db/db compared to control and male db/db mice, while impairment of sodium nitroprusside relaxations was only observed in aorta from male db/db mice. The remodeling in the coronary arteries and aorta suggests an adaptation of the arterial wall to the reduced flow velocity with sex-specific differences in the passive properties of aorta and coronary arteries. The findings of less distensible arteries and more pronounced endothelial dysfunction in female compared to male diabetic mice may have implications for the observed higher incidence of macrovascular complications in diabetic women.

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Section: Introductionmentioning

confidence: 99%

Endothelial Dysfunction and Passive Changes in the Aorta and Coronary Arteries of Diabetic db/db Mice

Beck

Comerma-Steffensen

et al. 2020

Front. Physiol.

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“…BJP guidelines must be adhered to, using editorials as a reference Curtis et al, 2018;Docherty et al, 2019;George et al, 2017;George et al, 2019). Checklists are available on BJP website.…”

Section: Has a Positive Control Been Used?mentioning

confidence: 99%

A practical guide for transparent reporting of research on natural products in the British Journal of Pharmacology: Reproducibility of natural product research

Izzo

Teixeira

Alexander

et al. 2020

British J Pharmacology

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190

181

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“…However, our study explored the mechanism of morphine tolerance only in male animals. Because sex differences may affect the pharmacokinetics and pharmacodynamics of drugs (Docherty et al, 2019), our findings may not be applicable to female rats. The roles of PDGFRβ and HSP27 in the mechanism of morphine tolerance in female animals need to be further explored.…”

Section: Discussionmentioning

confidence: 98%

Spinal heat shock protein 27 participates in PDGFRβ‐mediated morphine tolerance through PI3K/Akt and p38 MAPK signalling pathways

Peng

Jia

et al. 2020

British J Pharmacology

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Background and Purpose: The development of antinociceptive morphine tolerance is a clinically intractable problem. Earlier work has demonstrated the pivotal roles of PDGF and its receptor PDGFRβ in morphine tolerance. Here, we have investigated the role of spinal heat shock protein 27 (HSP27) in morphine tolerance and its relationship with PDGFRβ activation. Experimental Approach: Rats were treated with morphine for 9 days, and its antinociceptive effect against thermal pain was evaluated by a tail-flick latency test. Western blot, real-time PCR, immunofluorescent staining, and various antagonists, agonists, and siRNA lentiviral vectors elucidated the roles of HSP27, PDGFRβ, and related signalling pathways in morphine tolerance. Key Results: Chronic morphine administration increased expression and phosphorylation of HSP27 in the spinal cord. Down-regulating HSP27 attenuated the development of morphine tolerance. PDGFRβ antagonism inhibited HSP27 activation and attenuated and reversed morphine tolerance. PDGFRβ induction increased HSP27 expression and activation and partly decreased morphine analgesia. PDGFRβ inhibition reduced Akt and p38 MAPK activity in morphine tolerance. PI3K and p38 inhibitors reversed morphine tolerance and suppressed morphine-induced HSP27 phosphorylation. Conclusion and Implications: This study demonstrated for the first time that spinal HSP27 participates in PDGFRβ-mediated morphine tolerance via the PI3K/Akt and p38 MAPK signalling pathways. These findings suggest a potential clinical strategy for prolonging the antinociceptive effects of opioids during long-term pain control.

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Sex: A change in our guidelines to authors to ensure that this is no longer an ignored experimental variable

Cited by 60 publications

References 31 publications

Endothelial Dysfunction and Passive Changes in the Aorta and Coronary Arteries of Diabetic db/db Mice

Endothelial Dysfunction and Passive Changes in the Aorta and Coronary Arteries of Diabetic db/db Mice

A practical guide for transparent reporting of research on natural products in the British Journal of Pharmacology: Reproducibility of natural product research

Spinal heat shock protein 27 participates in PDGFRβ‐mediated morphine tolerance through PI3K/Akt and p38 MAPK signalling pathways

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