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 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 microg/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(omega)-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.
Diaz
Jessica
J
Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824-1317, USA.
Ni
Wei
W
Thompson
Janice
J
King
Andrew
A
Fink
Gregory D
GD
Watts
Stephanie W
SW
D000818:Animals; D000959:Antihypertensive Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects*; D003900:Desoxycorticosterone; D006973:Hypertension / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000502:physiology; D019335:Nitroarginine; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*
D000959:Antihypertensive Agents; D019335:Nitroarginine; D012701:Serotonin; D003900:Desoxycorticosterone; D019001:Nitric Oxide Synthase