Abstract P617: Actions on the Splanchnic Venous System Contribute to 5-HT-induced Hypotension

Abstract

Infusion of serotonin (5-hydroxytryptamine, 5-HT) into conscious normotensive and hypertensive rats causes a sustained reduction in systemic blood pressure. Imaging studies reveal that the blood pressure fall is closely associated with dilation of the large splanchnic veins (mesenteric, portal and abdominal vena cava), suggesting that active venodilation contributes to the fall in blood pressure. In fact, isolated splanchnic veins dilate directly to 5-HT via activation of the 5-HT 7 receptor, and a 5-HT 7 receptor antagonist prevents the 5-HT induced fall in blood pressure. To determine if the splanchnic venodilation caused by 5-HT is active or passive, anesthetized male Sprague Dawley rats were instrumented with arterial and venous lines for pressure measurements and 5-HT administration, respectively, while splanchnic veins were imaged using the Vevo® 2100 Ultrasound system. Measures were made relative to baselines measures. Within 5 minutes of infusion, 5-HT (25 ug/kg/min) caused an initial fall in portal vein pressure (~8-10% reduction) accompanied by dilation of the portal vein (~40% increase). No changes were seen in the dimensions or pressure of the abdominal vena cava at this time. Mean arterial blood pressure was reduced (>40% reduction). All of these changes were prevented by pretreatment with the 5-HT 7 receptor antagonist SB269970. SB269970 during 5-HT infusion also caused an immediate reversal of changes in blood pressure and venous dimensions. Thus, active dilation of the pre-hepatic splanchnic venous system may be an early cause of 5-HT-induced hypotension. A more chronic experiment was performed in rats that were instrumented with a new dual channel radiotelemeter for concomitant measure of systemic and portal pressure in the conscious state. Within one hour after initiation of 5-HT infusion, portal venous pressure was elevated 38±0.2% above baseline (n=3) versus vehicle infused animals (4±0.3% above baseline; n=3), suggesting an action of 5-HT on intrahepatic venous resistance. Within 24 hours, portal pressure elevation resolved but blood pressure remained reduced. Collectively these data highlight the portal venous circulation as an important site of action for 5-HT in causing acute and chronic falls in systemic blood pressure.