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CARDIOVASCULAR

5-Hydroxytryptamine Lowers Blood Pressure in Normotensive and Hypertensive Rats

Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan

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 administration 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 hypertensive and sham normotensive rat were used. Animals were implanted with minipumps that delivered 5-HT (or vehicle) at a rate of 25 µg/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-administered rats (peak fall arterial pressure, 91 ± 14 mm Hg) compared 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-administered (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 and DOCA-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.

Address correspondence to: Dr. Stephanie W. Watts, Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824-1317. E-mail: wattss{at}msu.edu

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				S. W. Watts The beginning of a fantastic, unanswered question: is 5-HT involved in systemic hypertension? Am J Physiol Heart Circ Physiol, September 1, 2008; 295(3): H915 - H916. [Abstract] [Full Text] [PDF]