[Effect of ketanserin on blood pressure in rats].
Ketanserin, a selective serotonergic (5-HT2) antagonist, also has affinity for alpha 1-adrenoceptors. It is not clear whether the hypotensive mechanism of ketanserin is due to its antagonistic action to 5-HT2 receptor or to its affinity for alpha 1 adrenoceptors. The hypotensive mechanism of ketanserin was studied in both stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar Kyoto rats (WKY). Anesthetized rats were used (alpha-chloralose + urethane, i.p.). Up to 3 ml of blood was drawn from each rat for analysis. Plasma norepinephrine (NE) was determined by radioenzymatic assay. Plasma serotonin (5-HT) was determined by HPLC-ECD. Adrenal nerve discharges were counted by a digital pulse counter. Ketanserin (0.5 mg/kg, 5.0 mg/kg, i.v.) produced a dose-dependent reduction of mean arterial pressure (MAP) in both SHRSP and WKY. MAP of SHRSP decreased significantly as compared with WKY. Both plasma NE and 5-HT showed a tendency to increase during ketanserin administration (5.0 mg/kg, i.v.). Ketanserin significantly antagonized the BP response induced by exogenously injected 5-HT (30 micrograms/kg) and NE (10 micrograms/kg). Adrenal nerve activity was reduced in parallel with the decrease in BP and HR. These findings suggest that ketanserin produced a decrease in BP via both peripheral and central action in rats.
Sano
M
M
Minami
M
M
Togashi
H
H
Yoshioka
M
M
Tochihara
M
M
Hirokami
M
M
Saito
H
H
D000311:Adrenal Glands / Q000294:innervation; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006897:Hydroxyindoleacetic Acid / Q000097:blood; D007650:Ketanserin; D008297:Male; D009638:Norepinephrine / Q000097:blood; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012701:Serotonin / Q000097:blood; D013564:Sympathetic Nervous System / Q000187:drug effects
D000959:Antihypertensive Agents; D010880:Piperidines; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D007650:Ketanserin; D009638:Norepinephrine