{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T06:56:46Z","timestamp":1774940206361,"version":"3.50.1"},"reference-count":29,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2020,10,22]],"date-time":"2020-10-22T00:00:00Z","timestamp":1603324800000},"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":["Experimental Physiology"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:sec><jats:title>New Findings<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p><jats:bold>What is the central question of this study?<\/jats:bold><\/jats:p><jats:p>What mechanisms account for the hypotension observed during chronic elevations in circulating 5\u2010hydroxytryptamine in rats?<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p><jats:bold>What is the main finding and its importance?<\/jats:bold><\/jats:p><jats:p>Chronic 5\u2010hydroxytryptamine\u2010induced hypotension requires continued activation of the 5\u2010HT<jats:sub>7<\/jats:sub> receptor subtype but does <jats:italic>not<\/jats:italic> require NO, an outcome that resolves previous conflicting results. Therapeutic interruption of the hypotensive actions of 5\u2010HT under pathophysiological conditions can only be achieved through blockade of the 5\u2010HT<jats:sub>7<\/jats:sub> receptor.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Low dose infusion of 5\u2010hydroxytryptamine (5\u2010HT) to rats causes both an acute and a chronic fall in arterial blood pressure. The 5\u2010HT<jats:sub>7<\/jats:sub> receptor subtype plays a critical part in the observed hypotension. Acute (minutes to hours) 5\u2010HT infusion shows no depressor role for nitric oxide (NO), but 5\u2010HT depressor responses under chronic conditions suggest that NO production may be critical. We test the hypothesis that NO contributes to the chronic, but not the acute, depressor response to 5\u2010HT. We compared the role of NO and 5\u2010HT<jats:sub>7<\/jats:sub> receptors in 5\u2010HT\u2010induced hypotension under acute and chronic conditions in the same animal. Mean arterial pressure and heart rate were measured by radiotelemetry in conscious rats during 5\u00a0days of saline or 5\u2010HT (25\u00a0\u03bcg\u00a0kg<jats:sup>\u22121<\/jats:sup>\u00a0min<jats:sup>\u22121<\/jats:sup>; osmotic pump) infusion and for 2\u00a0days after infusion was stopped. To quantify the contributions of NO and the 5\u2010HT<jats:sub>7<\/jats:sub> receptor to 5\u2010HT\u2010induced hypotension, the nitric oxide synthase (NOS) inhibitor <jats:sc>l<\/jats:sc>\u2010NAME or the selective 5\u2010HT<jats:sub>7<\/jats:sub> receptor antagonist SB\u2010267790 were given at 1, 3 and 5\u00a0days of chronic infusion, and 1 day after 5\u2010HT infusion pumps were removed. <jats:italic>N<\/jats:italic><jats:sup>\u03c9<\/jats:sup>\u2010Nitro\u2010<jats:sc>l<\/jats:sc>\u2010arginine methyl ester <jats:sc>(l\u2010NAME)<\/jats:sc> caused a pressor response of the same magnitude in the absence or presence of 5\u2010HT infusion. Conversely, SB\u2010269970 did not affect mean arterial pressure in the absence of 5\u2010HT infusion and reversed the 5\u2010HT\u2010induced depressor response at each time point. Our findings demonstrate that acute and chronic 5\u2010HT\u2010induced hypotension does not require NOS activation but does require continued activation of the 5\u2010HT<jats:sub>7<\/jats:sub> receptor.<\/jats:p><\/jats:sec>","DOI":"10.1113\/ep088919","type":"journal-article","created":{"date-parts":[[2020,10,14]],"date-time":"2020-10-14T13:33:10Z","timestamp":1602682390000},"page":"2025-2032","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Activation of the 5\u2010HT<sub>7<\/sub> receptor but not nitric oxide synthase is necessary for chronic 5\u2010hydroxytryptamine\u2010induced hypotension"],"prefix":"10.1113","volume":"105","author":[{"given":"Bridget M.","family":"Seitz","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology Michigan State University  East Lansing MI USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory D.","family":"Fink","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Michigan State University  East Lansing MI USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9653-6357","authenticated-orcid":false,"given":"Stephanie W.","family":"Watts","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Michigan State University  East Lansing MI USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,10,22]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2013.05.010"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(92)90544-E"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.acvd.2016.08.002"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.60.042307.110802"},{"key":"e_1_2_8_6_1","first-page":"S39","article-title":"Serotonin levels in hypertension","volume":"4","author":"Biondi M. 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