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The ((P)RR) is expressed throughout the body, including the vasculature, however, the direct effect of prorenin on arterial contractility is yet to be determined. Within rat mesenteric arteries, immunostaining and proximity ligation assays were used to determine the interacting partners of (P)RR in freshly isolated vascular smooth muscle cells (VSMCs). Wire myography examined the functional effect of prorenin. Simultaneous changes in [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>\n                      <jats:italic>i<\/jats:italic>\n                    <\/jats:sub>\n                    and force were recorded in arteries loaded with Fura\u20102AM. Spontaneously transient outward currents were recorded via perforated whole\u2010cell patch\u2010clamp configuration in freshly isolated VSMCs. We found that the (P)RR is located within a distance of less than 40\u2009nm from the V\u2010ATPase, caveolin\u20101, ryanodine receptors, and large conductance Ca\n                    <jats:sup>2+<\/jats:sup>\n                    \u2010activated K\n                    <jats:sup>+<\/jats:sup>\n                    channels (BK\n                    <jats:sub>Ca<\/jats:sub>\n                    ) in VSMCs. [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>\n                      <jats:italic>i<\/jats:italic>\n                    <\/jats:sub>\n                    imaging and isometric tension recordings indicate that 1\u2009nM prorenin enhanced \u03b11\u2010adrenoreceptor\u2010mediated contraction, associated with an increased number of Ca\n                    <jats:sup>2+<\/jats:sup>\n                    waves, independent of voltage\u2010gated Ca\n                    <jats:sup>2+<\/jats:sup>\n                    channels activation. Incubation of VSMCs with 1\u2009nM prorenin decreased the amplitude and frequency of spontaneously transient outward currents and attenuated BK\n                    <jats:sub>Ca<\/jats:sub>\n                    \u2010mediated relaxation. Inhibition of the V\u2010ATPase with 100\u2009nM bafilomycin prevented prorenin\u2010mediated inhibition of BK\n                    <jats:sub>Ca<\/jats:sub>\n                    \u2010derived relaxation. Renin (1\u2009nM) had no effect on BK\n                    <jats:sub>Ca<\/jats:sub>\n                    \u2010mediated relaxation. In conclusion, prorenin enhances arterial contractility by inhibition of BK\n                    <jats:sub>Ca<\/jats:sub>\n                    and increasing intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    release. It is likely that this effect is mediated through a local shift in pH upon activation of the (P)RR and stimulation of the V\u2010ATPase.\n                  <\/jats:p>","DOI":"10.1096\/fj.202301480","type":"journal-article","created":{"date-parts":[[2023,11,24]],"date-time":"2023-11-24T19:41:40Z","timestamp":1700854900000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Acute, pro\u2010contractile effects of prorenin on rat mesenteric arteries"],"prefix":"10.1096","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3276-5887","authenticated-orcid":false,"given":"Salom\u00e9","family":"Rognant","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences University of Copenhagen  Copenhagen N Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3796-6090","authenticated-orcid":false,"given":"Samuel N.","family":"Baldwin","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences University of Copenhagen  Copenhagen N Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2408-0909","authenticated-orcid":false,"given":"Harry A. T.","family":"Pritchard","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health Manchester University Teaching Hospitals NHS Foundation Trust, University of Manchester  Manchester UK"},{"name":"Geoffrey Jefferson Brain Research Centre, The Manchester Academic Health Science Centre, Northern Care Alliance NHS Foundation Trust University of Manchester  Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5274-4189","authenticated-orcid":false,"given":"Adam","family":"Greenstein","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health Manchester University Teaching Hospitals NHS Foundation Trust, University of Manchester  Manchester UK"},{"name":"Geoffrey Jefferson Brain Research Centre, The Manchester Academic Health Science Centre, Northern Care Alliance NHS Foundation Trust University of Manchester  Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1777-7938","authenticated-orcid":false,"given":"Kirstine","family":"Calloe","sequence":"additional","affiliation":[{"name":"Section for Pathobiological Sciences, Department of Veterinary and Animal Sciences University of Copenhagen  Frederiksberg C Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2618-4015","authenticated-orcid":false,"given":"Christian","family":"Aalkjaer","sequence":"additional","affiliation":[{"name":"Department of Biomedicine Aarhus University  Aarhus C Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9903-714X","authenticated-orcid":false,"given":"Thomas A.","family":"Jepps","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences University of Copenhagen  Copenhagen N 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