Effect of N(G)-nitro-L-arginine methyl ester on the hypotensive and hypertensive responses to 5-hydroxytryptamine in pithed rats.
The potential ability of the nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME; 1 to 10 mg/kg), to modulate blood pressure responses to 5-hydroxytryptamine (5-HT), 5-carboxamidotryptamine (5-CT) and (1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane) (DOI) was studied in pithed rats. The hypotensive responses to 5-HT in the presence of ketanserin were augmented by L-NAME as well as by phenylephrine infusion, both of which themselves increased blood pressure. L-NAME also tended to prolong the duration of the response of 5-HT. Likewise, the hypotensive responses to 5-CT were potentiated. The magnitude of the hypertensive responses to 5-HT was unaffected by L-NAME or phenylephrine. However, in contrast to phenylephrine, L-NAME prolonged the duration of these responses. The magnitude and duration (middle dose only) of the hypertensive responses to DOI were augmented by L-NAME, but phenylephrine was ineffective. These results suggest that L-NAME increases blood pressure, probably by inhibiting the basal release of NO in animals with a low vascular tone. However, the hypotensive responses to 5-HT and 5-CT seem to be largely independent of NO release by the endothelium, but the hypertensive responses to 5-HT and DOI appear to be limited by the release of NO in the pithed rat.
Van Gelderen
E M
EM
Department of Pharmacology, Faculty of Medicine and Health Sciences, Erasmus University Rotterdam, Netherlands.
Saxena
P R
PR
D000818:Animals; D001067:Appetite Depressants / Q000494:pharmacology*; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced; D007022:Hypotension / Q000139:chemically induced; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D001067:Appetite Depressants; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D001120:Arginine; D007650:Ketanserin; D019331:NG-Nitroarginine Methyl Ester