Reciprocal potentiation of a vasoconstrictor response between 5-hydroxytryptamine and clonidine in the perfused mesenteric vascular bed of the rat.
The interaction between 5-hydroxytryptamine (5-HT) and clonidine, an alpha 2-adrenoceptor agonist, was investigated in the isolated perfused mesenteric vascular bed of the rat. Clonidine itself did not cause vasoconstriction even at 300 micrograms. However, clonidine in the presence of 5-HT (10 and 100 nM) caused a marked vasoconstriction in a dose range of 0.1 micrograms to 300 micrograms. Prazosin inhibited the clonidine response, whereas yohimbine did not. The potency of prazosin against clonidine was less than that against an alpha 1-adrenoceptor agonist phenylephrine. Therefore, it is suggested that clonidine activated alpha 1-like adrenoceptors. 5-HT also potentiated the vasoconstrictor response to perivascular nerve stimulation, exogenous norepinephrine (NE) and phenylephrine. Calcium entry blockade by nicardipine (0.1 microM) reduced the response to clonidine in the presence of 5-HT, whereas that to phenylephrine in the presence or absence of 5-HT was not reduced. On the other hand, clonidine (0.01-1 microM) potentiated the vasoconstrictor effect of 5-HT more than NE did. Ouabain (1 microgram/ml) enabled clonidine to exhibit an agonistic action, and also enhanced the contractile response to 5-HT. In conclusion, 5-HT modulated the vasoconstrictor effect of clonidine, and the vasoconstriction with 5-HT was also facilitated by clonidine reciprocally. It is possible that a partial depolarization of the cell membrane is the common mechanism for their reciprocal potentiation.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology*; D015237:Dinoprost; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010042:Ouabain / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011460:Prostaglandins F / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000494:pharmacology*; D013152:Splanchnic Circulation / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects*; D015016:Yohimbine / Q000494:pharmacology
D011460:Prostaglandins F; D010656:Phenylephrine; D015016:Yohimbine; D012701:Serotonin; D010042:Ouabain; D015237:Dinoprost; D003000:Clonidine