5-Hydroxytryptamine lowers blood pressure in normotensive and hypertensive rats

Arterial hyper-responsiveness to 5-hydroxytryptamine (5-HT) is a hallmark of hypertension, and plasma levels of free 5-HT are elevated in hypertension. We hypothesized that chronic admin-istration of 5-HT would cause blood pressure to 1) rise in normotensive rats and 2) rise significantly more in hypertensive rats. The deoxycorticosterone acetate (DOCA)-salt hyperten-sive and sham normotensive rat were used. Animals were im-planted with minipumps that delivered 5-HT (or vehicle) at a rate of 25 g/kg/min for 7 days. Free plasma 5-HT was elevated significantly by this protocol. Within 48 h, mean arterial blood pressure measured telemetrically decreased in sham (106 2 to 83 2 mm Hg) and in DOCA-salt hypertensive (166 9 to 112 3 mm Hg) rats; vehicle did not change blood pressure in either group. Ganglionic blockade (hexamethonium) reduced blood pressure to a greater magnitude in DOCA vehicle-admin-istered rats (peak fall arterial pressure, 91 14 mm Hg) com-pared with DOCA 5-HT-administered rats (40 6 mm Hg). Maximal acetylcholine-induced (NO-dependent) relaxation in phenylephrine-contracted aortic strips was greater in 5-HT-administered (69.2 9.1 % relaxation) versus vehicle-adminis-tered (39.7 14.2%) DOCA rats; aortic endothelial cell nitric oxide synthase expression was higher in the 5-HT- versus vehicle-administered DOCA-salt rats. In normotensive andDOCA-salt hypertensive rats, the nitric oxide synthase (NOS) inhibitor N-nitro-L-arginine (0.5 g/l in water) prevented the fall in blood pressure to 5-HT. We conclude that chronic exogenous 5-HT reduces blood pressure in normotensive and hypertensive rats through mechanisms critically dependent on NOS. Serotonin [5-hydroxytryptamine (5-HT)] was discovered and characterized over 60 years ago by the Italian scientis