Abstract 642: NOS-dependent Increase In Splanchnic Blood Flow Causes The Hypotensive Response To 24-hour 5-HT Infusion
Long-term serotonin (5-hydroxytryptamine, 5-HT) infusion produces a sustained reduction in mean arterial pressure (MAP) and elicits a decrease in total peripheral resistance (TPR) through a mechanism dependent on nitric oxide synthase (NOS) in rats. We sought to determine if the reduction in TPR induced by 5-HT is caused by NOS-dependent relaxation of vessels to all major organs of the body or selective action on a single vascular bed. Alzet mini-pumps containing vehicle (saline) or 5-HT (25 μg/kg/min) were implanted in male Sprague Dawley rats. One-week prior to pump implantation, rats were either: (1) switched to drinking water containing the NOS inhibitor N-nitro-L-arginine (L-NNA; 0.5 g/L), or (2) maintained on tap water. 5-HT reduced MAP after 24 hours (veh = 87±3, 5-HT = 75±2 mm Hg; p<0.05), which was prevented by L-NNA (L-NNA/5-HT= 115 ±10 mm Hg; p<0.05). After 24 hours of 5-HT infusion, yellow-green fluorescent microspheres, used to determine blood flow (300, 000 spheres; size 15μm), were introduced into the left ventricle of the heart. Microspheres were recovered in arterial reference blood sample and organs using sedimentation through centrifugation. The fluorescence intensity of the dye extracted from the microspheres was measured by spectrophotometery. 5-HT significantly decreased resistance to the spleen (48%), small intestine (35%), and adrenal (70%) compared to vehicle-treated animals, and this decrease was abolished by L-NNA. By contrast, resistance to the ear (175%) was increased by 5-HT. Resistance to other organs (brain, liver, lungs, kidneys and muscle) did not show a statistically significant reduction by 5-HT. Collectively, these findings underscore the importance of the splanchnic circulation and NOS in 5-HT-induced reduction in blood pressure.
- © 2013 by American Heart Association, Inc.