title: 5-hydroxytryptamine (5-HT) reduces total peripheral resistance during chronic infusion: direct arterial mesenteric relaxation is not involved.
abstract: Serotonin (5-hydroxytryptamine; 5-HT) delivered over 1 week results in a sustained fall in blood pressure in the sham and deoxycorticosterone acetate (DOCA)-salt rat. We hypothesized 5-HT lowers blood pressure through direct receptor-mediated vascular relaxation. In vivo, 5-HT reduced mean arterial pressure (MAP), increased heart rate, stroke volume, cardiac index, and reduced total peripheral resistance during a 1 week infusion of 5-HT (25 µg/kg/min) in the normotensive Sprague Dawley rat. The mesenteric vasculature was chosen as an ideal candidate for the site of 5-HT receptor mediated vascular relaxation given the high percentage of cardiac output the site receives. Real-time RT-PCR demonstrated that mRNA transcripts for the 5-HT2B, 5-HT1B, and 5-HT7 receptors are present in sham and DOCA-salt superior mesenteric arteries. Immunohistochemistry and Western blot validated the presence of the 5-HT2B, 5- HT1B and 5-HT7 receptor protein in sham and DOCA-salt superior mesenteric artery. Isometric contractile force was measured in endothelium-intact superior mesenteric artery and mesenteric resistance arteries in which the contractile 5- HT2A receptor was antagonized. Maximum concentrations of BW-723C86 (5- HT2B agonist), CP 93129 (5-HT1B agonist) or LP-44 (5-HT7 agonist) did not relax the superior mesenteric artery from DOCA-salt rats vs. vehicle. Additionally, 5-HT (10-9 M to 10-5 M) did not cause relaxation in either contracted mesenteric resistance arteries or superior mesenteric arteries from normotensive Sprague- Dawley rats. Thus, although 5-HT receptors known to mediate vascular relaxation are present in the superior mesenteric artery, they are not functional, and are therefore not likely involved in a 5-HT-induced fall in total peripheral resistance and MAP.
authors.affiliation: Department of Pharmacology and Toxicology, Michigan State University, East, Lansing, MI 48824-1317, USA.
authors.forename: Robert Patrick
authors.initials: RP
authors.lastname: Davis
authors.forename: Jill
authors.initials: J
authors.lastname: Pattison
authors.forename: Janice M
authors.initials: JM
authors.lastname: Thompson
authors.forename: Ruslan
authors.initials: R
authors.lastname: Tiniakov
authors.forename: Karie E
authors.initials: KE
authors.lastname: Scrogin
authors.forename: Stephanie W
authors.initials: SW
authors.lastname: Watts
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003900:Desoxycorticosterone; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D008901:Mineralocorticoids; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects*; D014664:Vasodilation
chemical_list: D008901:Mineralocorticoids; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D003900:Desoxycorticosterone