Antihypertensive effect of chronic i.v. administration of 5-carboxamidotryptamine in spontaneously hypertensive rats.
The effects of chronic i.v. administration of the serotonin 5-HT1 receptor agonist, 5-carboxamidotryptamine (5-CT), on blood pressure (BP), heart rate (HR) and baroreflex sensitivity were studied in Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Acute i.v. injection of increasing doses of 5-CT resulted in a dose-dependent reduction in mean arterial pressure (MAP) in SHR and WKY with concomitant tachycardia. In chronic experiments, 5-CT (15.0 micrograms/kg per day) or vehicle (24.0 microliters/day) was infused i.v. for 7 days, using osmotic minipumps. Systolic blood pressure (SBP) and HR were monitored daily before and during infusions. In SHR (n = 8) and WKY rats (n = 9) receiving 5-CT, a significant reduction in SBP was observed during the infusion period. HR was slightly increased in WKY rats on days 1 and 2. There were no HR changes in the SHR group. The fall in SBP was significantly larger in the SHR than in the WKY rats. Baroreflex sensitivity on day 7 was significantly greater in 5-CT-treated SHR than in control rats. There was no change in baroreflex sensitivity in WKY rats. Administration of a single dose of 5-CT (0.5 microgram/kg i.v.) on day 7 of infusion resulted in attenuated responses in WKY rats while SHR responded as their respective controls. Our data suggest that chronic administration of 5-CT results in a sustained antihypertensive effect. This is associated with an improved BRS in the SHR either as a consequence of a resetting of the baroreflex due to sustained lowering of BP or a direct action of 5-CT on baroreflex sensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)
Balasubramaniam
G
G
Department of Pharmacology, Faculty of Medicine, National University of Singapore, Kent Ridge.
Lee
H S
HS
Mah
S C
SC
D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D015918:Infusion Pumps, Implantable; D007275:Injections, Intravenous; D008297:Male; D011311:Pressoreceptors / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects; D012701:Serotonin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*
D000959:Antihypertensive Agents; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D012701:Serotonin; C047087:5-carboxamidotryptamine