{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:23:36Z","timestamp":1787016216992,"version":"build-2736575974"},"reference-count":85,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2018,3,5]],"date-time":"2018-03-05T00:00:00Z","timestamp":1520208000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000145","name":"Alberta Innovates - Health Solutions","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000145","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<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>\n                            In isolated resistance arteries, endothelial modulation of vasoconstrictor responses to \u03b1\n                            <jats:sub>1<\/jats:sub>\n                            \u2010adrenoceptor agonists occurs via a process termed myoendothelial feedback: localized inositol trisphosphate (InsP\n                            <jats:sub>3<\/jats:sub>\n                            )\u00addependent Ca\n                            <jats:sup>2+<\/jats:sup>\n                            transients activate intermediate conductance Ca\n                            <jats:sup>2+<\/jats:sup>\n                            \u00adactivated K\n                            <jats:sup>+<\/jats:sup>\n                            (IK\n                            <jats:sub>Ca<\/jats:sub>\n                            ) channels, hyperpolarizing the endothelial membrane potential to limit further reductions in vessel diameter.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            We demonstrate that IK\n                            <jats:sub>Ca<\/jats:sub>\n                            channel\u2010mediated myoendothelial feedback limits responses of isolated mesenteric arteries to noradrenaline and nerve stimulation, but not to the thromboxane A\n                            <jats:sub>2<\/jats:sub>\n                            mimetic U46619 or to increases in intravascular pressure.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            In contrast, in the intact mesenteric bed, although responses to exogenous noradrenaline were limited by IK\n                            <jats:sub>Ca<\/jats:sub>\n                            channel\u2010mediated myoendothelial feedback, release of NO and activation of endothelial small conductance Ca\n                            <jats:sup>2+<\/jats:sup>\n                            \u00adactivated K\n                            <jats:sup>+<\/jats:sup>\n                            (SK\n                            <jats:sub>Ca<\/jats:sub>\n                            ) channels in response to increases in shear stress appeared to be the primary mediators of endothelial modulation of vasoconstriction.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            We propose that (1) the functional contribution of myoendothelial feedback to arterial tone is determined by the nature of the vasoconstrictor stimulus, and (2) although IK\n                            <jats:sub>Ca<\/jats:sub>\n                            channel\u2010mediated myoendothelial feedback may contribute to local control of arterial diameter, in the intact vascular bed, increases in shear stress may be the major stimulus for engagement of the endothelium during vasoconstriction.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      Constriction of isolated resistance arteries in response to \u03b1\n                      <jats:sub>1<\/jats:sub>\n                      \u2010adrenoceptor agonists is limited by reciprocal engagement of inhibitory endothelial mechanisms via myoendothelial feedback. In the current model of feedback, agonist stimulation of smooth muscle cells results in localized InsP\n                      <jats:sub>3<\/jats:sub>\n                      \u00addependent Ca\n                      <jats:sup>2+<\/jats:sup>\n                      transients that activate endothelial IK\n                      <jats:sub>Ca<\/jats:sub>\n                      channels. The subsequent hyperpolarization of the endothelial membrane potential then feeds back to the smooth muscle to limit further reductions in vessel diameter. We hypothesized that the functional contribution of InsP\n                      <jats:sub>3<\/jats:sub>\n                      \u2013IK\n                      <jats:sub>Ca<\/jats:sub>\n                      channel\u2010mediated myoendothelial feedback to limiting arterial diameter may be influenced by the nature of the vasoconstrictor stimulus. To test this hypothesis, we investigated the functional role of myoendothelial feedback in modulating responses of rat mesenteric resistance arteries to the adrenoceptor agonist noradrenaline, the thromboxane A\n                      <jats:sub>2<\/jats:sub>\n                      mimetic U46619, increases in intravascular pressure and stimulation of perivascular sympathetic nerves. In isolated arteries, responses to noradrenaline and stimulation of sympathetic nerves, but not to U46619 and increases in intravascular pressure, were modulated by IK\n                      <jats:sub>Ca<\/jats:sub>\n                      channel\u2010dependent myoendothelial feedback. In the intact mesenteric bed perfused under conditions of constant flow, responses to exogenous noradrenaline were modulated by myoendothelial feedback, but shear stress\u2010induced release of NO and activation of endothelial SK\n                      <jats:sub>Ca<\/jats:sub>\n                      channels appeared to be the primary mediators of endothelial modulation of vasoconstriction to agonists and nerve stimulation. Thus, we propose that myoendothelial feedback may contribute to local control of diameter within arterial segments, but at the level of the intact vascular bed, increases in shear stress may be the major stimulus for engagement of the endothelium during vasoconstriction.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/jp274797","type":"journal-article","created":{"date-parts":[[2018,2,7]],"date-time":"2018-02-07T04:52:56Z","timestamp":1517979176000},"page":"1181-1197","source":"Crossref","is-referenced-by-count":24,"title":["Vasoconstrictor stimulus determines the functional contribution of myoendothelial feedback to mesenteric arterial tone"],"prefix":"10.1113","volume":"596","author":[{"given":"R.","family":"Wei","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine and Dentistry University of Alberta Edmonton Alberta T6G 2H7 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. 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