{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T13:25:08Z","timestamp":1778246708337,"version":"3.51.4"},"reference-count":62,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2024,4,24]],"date-time":"2024-04-24T00:00:00Z","timestamp":1713916800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:sec><jats:title>Abstract<\/jats:title><jats:p>During the urine storage phase, tonically contracting urethral musculature would have a higher energy consumption than bladder muscle that develops phasic contractions. However, ischaemic dysfunction is less prevalent in the urethra than in the bladder, suggesting that urethral vasculature has intrinsic properties ensuring an adequate blood supply. Diameter changes in rat or mouse urethral arterioles were measured using a video\u2010tracking system. Intercellular Ca<jats:sup>2+<\/jats:sup> dynamics in arteriolar smooth muscle (SMCs) and endothelial cells were visualised using NG2\u2010 and parvalbumin\u2010GCaMP6 mice, respectively. Fluorescence immunohistochemistry was used to visualise the perivascular innervation. In rat urethral arterioles, sympathetic vasoconstrictions were predominantly suppressed by \u03b1,\u03b2\u2010methylene ATP (10\u00a0\u03bcM) but not prazosin (1\u00a0\u03bcM). Tadalafil (100\u00a0n<jats:sc>M<\/jats:sc>), a PDE5 inhibitor, diminished the vasoconstrictions in a manner reversed by <jats:italic>N<\/jats:italic>\u2010\u03c9\u2010propyl\u2010<jats:sc>l<\/jats:sc>\u2010arginine hydrochloride (<jats:sc>l<\/jats:sc>\u2010NPA, 1\u00a0\u03bcM), a neuronal NO synthesis (nNOS) inhibitor. Vesicular acetylcholine transporter immunoreactive perivascular nerve fibres co\u2010expressing nNOS were intertwined with tyrosine hydroxylase immunoreactive sympathetic nerve fibres. In phenylephrine (1\u00a0\u03bcM) pre\u2010constricted rat or mouse urethral arterioles, nerve\u2010evoked vasodilatations or transient SMC Ca<jats:sup>2+<\/jats:sup> reductions were largely diminished by <jats:sc>l<\/jats:sc>\u2010nitroarginine (<jats:sc>l<\/jats:sc>\u2010NA, 10\u00a0\u03bcM), a broad\u2010spectrum NOS inhibitor, but not by <jats:sc>l<\/jats:sc>\u2010NPA. The CGRP receptor antagonist BIBN\u20104096 (1\u00a0\u03bcM) shortened the vasodilatory responses, while atropine (1\u00a0\u03bcM) abolished the <jats:sc>l<\/jats:sc>\u2010NA\u2010resistant transient vasodilatory responses. Nerve\u2010evoked endothelial Ca<jats:sup>2+<\/jats:sup> transients were abolished by atropine plus guanethidine (10\u00a0\u03bcM), indicating its neurotransmitter origin and absence of non\u2010adrenergic non\u2010cholinergic endothelial NO release. In urethral arterioles, NO released from parasympathetic nerves counteracts sympathetic vasoconstrictions pre\u2010 and post\u2010synaptically to restrict arteriolar contractility.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp16057-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Despite a higher energy consumption of the urethral musculature than the bladder detrusor muscle, ischaemic dysfunction of the urethra is less prevalent than that of the bladder.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In the urethral arterioles, sympathetic vasoconstrictions are predominately mediated by ATP, not noradrenaline.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>NO released from parasympathetic nerves counteracts sympathetic vasoconstrictions by its pre\u2010synaptic inhibition of sympathetic transmission as well as post\u2010synaptic arteriolar smooth muscle relaxation.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Acetylcholine released from parasympathetic nerves contributes to endothelium\u2010dependent, transient vasodilatations, while CGRP released from sensory nerves prolongs NO\u2010mediated vasodilatations.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>PDE5 inhibitors could be beneficial to maintain and\/or improve urethral blood supply and in turn the volume and contractility of urethral musculature.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp285583","type":"journal-article","created":{"date-parts":[[2024,4,24]],"date-time":"2024-04-24T15:04:44Z","timestamp":1713971084000},"page":"2199-2226","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Nitrergic inhibition of sympathetic arteriolar constrictions in the female rodent urethra"],"prefix":"10.1113","volume":"602","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3877-4349","authenticated-orcid":false,"given":"Hikaru","family":"Hashitani","sequence":"first","affiliation":[{"name":"Department of Cell Physiology Graduate School of Medical Sciences Nagoya City University  Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2932-4693","authenticated-orcid":false,"given":"Retsu","family":"Mitsui","sequence":"additional","affiliation":[{"name":"Department of Cell Physiology Graduate School of Medical Sciences Nagoya City University  Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuuna","family":"Hirai","sequence":"additional","affiliation":[{"name":"Department of Cell Physiology Graduate School of Medical Sciences Nagoya City University  Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hidekazu","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Cell Physiology Graduate School of Medical Sciences Nagoya City University  Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyoko","family":"Miwa\u2010Nishimura","sequence":"additional","affiliation":[{"name":"Department of Cell Physiology Graduate School of Medical Sciences Nagoya City University  Nagoya 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