title: One-month serotonin infusion results in a prolonged fall in blood pressure in the deoxycorticosterone acetate (DOCA) salt hypertensive rat.
abstract: A 7-day infusion of serotonin (5-hydroxytryptamine, 5-HT) causes a sustained fall in elevated blood pressure in the male deoxycorticosterone acetate (DOCA)-salt rat. As hypertension is a long-term disease, we presently test the hypothesis that a longer (30 day) 5-HT infusion could cause a sustained fall in blood pressure in the established hypertensive DOCA-salt rat. This time period (∼4 weeks) was also sufficient to test whether 5-HT could attenuate the development of DOCA-salt hypertension. 5-HT (25 μg/kg/min; sc) or vehicle (Veh) was delivered via osmotic pump to (1) established DOCA-salt rats for one month, (2) Sprague-Dawley rats prior to DOCA-salt administration for one month, and blood pressure and heart rate measured telemetrically. On the final day of 5-HT infusion, free platelet poor plasma 5-HT concentrations were significantly higher in 5-HT versus Veh-infused rats, and mean arterial pressure was significantly lower in 5-HT-infused (135 ± 4 mmHg vs Veh-infused 151 ± 7 mmHg) established DOCA-salt rats. By contrast, 5-HT-infusion did not prevent the development of DOCA-salt hypertension (144 ± 7 mmHg vs Veh = 156 ± 6 mmHg). Isometric contraction of aortic strips was measured, and neither the potency nor maximum contraction to the alpha adrenergic receptor agonist phenylephrine (PE) or 5-HT were modified by infusion of 5-HT (established or preventative infusion), and maximum aortic relaxation to acetylcholine (ACh) was modestly but not significantly enhanced (∼15% improvement). This study demonstrates 5-HT is capable of lowering blood pressure in established DOCA-salt hypertensive rats over the course of one month in a mechanism that does not significantly modify or is dependent on modified vascular responsiveness. This finding opens the possibility that elevation of 5-HT levels could be useful in the treatment of hypertension.
authors: Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan, United States.
authors: Robert Patrick
authors: RP
authors: Davis
authors: Theodora
authors: T
authors: Szasz
authors: Hannah
authors: H
authors: Garver
authors: Robert
authors: R
authors: Burnett
authors: Nathan R
authors: NR
authors: Tykocki
authors: Stephanie W
authors: SW
authors: Watts
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D062186:Arterial Pressure / Q000187:drug effects; D003900:Desoxycorticosterone / Q000633:toxicity; D006973:Hypertension / Q000188:drug therapy*; D007262:Infusions, Intravenous; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D008901:Mineralocorticoids / Q000633:toxicity; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000959:Antihypertensive Agents; D008901:Mineralocorticoids; D012701:Serotonin; D003900:Desoxycorticosterone