{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T11:08:15Z","timestamp":1788433695870,"version":"build-2803163510"},"reference-count":85,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,3,2]],"date-time":"2025-03-02T00:00:00Z","timestamp":1740873600000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,3,1]],"date-time":"2025-03-01T00:00:00Z","timestamp":1740787200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      Diaphragm hyperaemia and regional blood flow distribution are impaired with ageing, potentially consequent to altered vascular structure and\/or diminished vasomotor function. Evidence from locomotory skeletal muscle suggests that age\u2010related diaphragm vasomotor dysfunction may be related to a blunted endothelium\u2010mediated vasodilatation, decreased nitric oxide (NO) bioavailability and\/or augmented reactive oxygen species (ROS) generation. We hypothesized that, in the medial costal diaphragm with old age, there would be fewer feed arteries (FAs) and impaired vasomotor function, via endothelium\u2010specific mechanisms, in first\u2010order (1A) arterioles. In young (Y) and old (O) Fischer\u2010344 rats, the number of medial costal diaphragm FAs was quantified. 1A arterioles (117\u2013220 \u00b5m) were isolated, cannulated and pressurized via hydrostatic reservoirs. Thereafter endothelium\u2010dependent (via ACh) vasodilatory responses were assessed. In a separate set of arterioles, ACh\u2010mediated dilatation was assessed before and after treatment with the superoxide dismutase mimetic Tempol (100 \u00b5\n                      <jats:sc>m<\/jats:sc>\n                      ) and Tempol plus the hydrogen peroxide (H\n                      <jats:sub>2<\/jats:sub>\n                      O\n                      <jats:sub>2<\/jats:sub>\n                      ) scavenger catalase (100 U\/ml). The average number of medial costal FAs was lower in the rat diaphragm with old age (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.001). Endothelium\u2010 and nitric oxide synthase (NOS)\u2010dependent vasodilatation was 21% lower in medial costal 1A arterioles from O rats (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.001). Tempol decreased ACh\u2010mediated vasodilatation of medial costal 1A arterioles from Y and O rats but did not eliminate age\u2010related differences. Tempol plus catalase further decreased ACh\u2010mediated vasodilatation in O but not Y vessels. In the medial costal diaphragm vasculature, ageing is associated with (1) arterial rarefaction, (2) impaired endothelium\u2010dependent vasodilatation via NOS\u2010 and ROS\u2010dependent mechanisms and (3) increased reliance on ROS\u2010mediated vasodilatation.\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp16596-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Old age blunts the hyperaemic response and alters regional blood flow distribution in the diaphragm. The effect of ageing on vascular structure and function in respiratory skeletal muscle is unknown.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>In young and old Fischer\u2010344 rats of both sexes, we quantified the number of feed arteries (FAs) and assessed the vasoreactivity of first\u2010order (1A) arterioles in the medial costal diaphragm.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The number of medial costal diaphragm FAs was lower in old rats. In 1A arterioles endothelium\u2010dependent vasodilatation was blunted, and reactive oxygen species (ROS)\u2010mediated vasodilatory signalling was greater in old rats.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>We found no evidence of sex differences in diaphragm macrovascular structure, endothelial function or ROS\u2010mediated signalling in young or old rats.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Our findings in the diaphragm vasculature with ageing provide a mechanistic basis for the age\u2010related deficits in diaphragm blood flow capacity.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Therapeutic interventions targeting the diaphragm vasculature to improve perfusion and oxygen delivery may reduce the burden of age\u2010related diaphragm dysfunction.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/jp287451","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T01:33:45Z","timestamp":1741743225000},"page":"1439-1459","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Ageing impairs endothelium\u2010dependent vasodilatation and alters redox signalling in diaphragm arterioles from male and female Fischer\u2010344 rats"],"prefix":"10.1113","volume":"603","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4435-4022","authenticated-orcid":false,"given":"Andrew G.","family":"Horn","sequence":"first","affiliation":[{"name":"Department of Kinesiology Kansas State University  Manhattan Kansas 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