{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T21:57:02Z","timestamp":1789509422150,"version":"build-2803163510"},"reference-count":34,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2009,1,21]],"date-time":"2009-01-21T00:00:00Z","timestamp":1232496000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2009,4]]},"abstract":"<jats:p>\n                    <jats:bold>WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT<\/jats:bold>\n                  <\/jats:p>\n                  <jats:p>\u2022\u2003It has been recognized for about 10 years that morphine is a veno\u2010dilator in man and that this effect may be related to histamine release.<\/jats:p>\n                  <jats:p>\n                    <jats:bold>WHAT THIS PAPER ADDS<\/jats:bold>\n                  <\/jats:p>\n                  <jats:p>\u2022\u2003This effect also occurs in the arteriolar system, with vasodilatation at doses of morphine that may have clinical relevance in patients with heart failure, or who abuse opioids.<\/jats:p>\n                  <jats:p>\u2022\u2003The effect is mediated by histamine release and actions of nitric oxide.<\/jats:p>\n                  <jats:p>\u2022\u2003The mechanisms of this effect of morphine are unclear, but suggest an alternative therapeutic target in vascular disease.<\/jats:p>\n                  <jats:p>\n                    <jats:bold>AIM<\/jats:bold>\n                    The mechanisms of action of morphine on the arterial system are not well understood. The aim was to report forearm vascular responses, and their mediation, to intra\u2010arterial morphine in healthy subjects.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>METHODS<\/jats:bold>\n                    Three separate protocols were performed: (i) dose ranging; (ii) acute tolerance; (iii) randomized crossover mechanistic study on forearm blood flow (FBF) responses to intrabrachial infusion of morphine using venous occlusion plethysmography. Morphine was infused either alone (study 1 and 2), or with an antagonist: naloxone, combined histamine\u20101 and histamine\u20102 receptor blockade or during a nitric oxide clamp.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>RESULTS<\/jats:bold>\n                    Morphine caused an increase in FBF at doses of 30\u2003\u00b5g\u2003min\n                    <jats:sup>\u22121<\/jats:sup>\n                    [3.25 (0.26)\u2003ml\u2003min\n                    <jats:sup>\u22121<\/jats:sup>\n                    \u2003100\u2003ml\n                    <jats:sup>\u22121<\/jats:sup>\n                    ][mean (SEM)] doubling at 100\u2003\u00b5g\u2003min\n                    <jats:sup>\u22121<\/jats:sup>\n                    to 5.23 (0.53)\u2003ml\u2003min\n                    <jats:sup>\u22121<\/jats:sup>\n                    \u2003100\u2003ml\n                    <jats:sup>\u22121<\/jats:sup>\n                    . Acute tolerance was not seen to 50\u2003\u00b5g\u2003min\n                    <jats:sup>\u22121<\/jats:sup>\n                    morphine, with increased FBF [3.96 (0.35)\u2003ml\u2003min\n                    <jats:sup>\u22121<\/jats:sup>\n                    \u2003100\u2003ml\n                    <jats:sup>\u22121<\/jats:sup>\n                    ] (\n                    <jats:italic>P<\/jats:italic>\n                    \u2003=\u20030.003), throughout the 30\u2010min infusion period. Vasodilatation was abolished by pretreatment with antihistamines (\n                    <jats:italic>P<\/jats:italic>\n                    \u2003=\u20030.008) and the nitric oxide clamp (\n                    <jats:italic>P<\/jats:italic>\n                    \u2003&lt;\u20030.001), but not affected by naloxone. The maximum FBF with pretreatment with combined H1\/H2 blockade was 3.06 (0.48) and 2.90 (0.17)\u2003ml\u2003min\n                    <jats:sup>\u22121<\/jats:sup>\n                    \u2003100\u2003ml\n                    <jats:sup>\u22121<\/jats:sup>\n                    after 30\u2003min, whereas with morphine alone it reached 4.3 (0.89)\u2003ml\u2003min\n                    <jats:sup>\u22121<\/jats:sup>\n                    \u2003100\u2003ml\n                    <jats:sup>\u22121<\/jats:sup>\n                    .\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>CONCLUSIONS<\/jats:bold>\n                    Intra\u2010arterial infusion of morphine into the forearm circulation causes vasodilatation through local histamine\u2010modulated nitric oxide release. Opioid receptor mechanisms need further exploration.\n                  <\/jats:p>","DOI":"10.1111\/j.1365-2125.2009.03364.x","type":"journal-article","created":{"date-parts":[[2009,1,21]],"date-time":"2009-01-21T11:49:58Z","timestamp":1232538598000},"page":"386-393","source":"Crossref","is-referenced-by-count":28,"title":["Morphine is an arteriolar vasodilator in man"],"prefix":"10.1111","volume":"67","author":[{"given":"Reza","family":"Afshari","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon R. J.","family":"Maxwell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Webb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. 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