Vasoconstrictor reaction to prostaglandins E1 and E2 in the isolated rat hindlimb mediated through serotonin release

The vasoconstrictor effects of prostaglandins E (PGEs) were studied in the isolated perfused hindlimbs of the rat. Doses of PGE1 in the range of 0.01-10 micrograms caused dose-dependent increases in perfusion pressure with rapid development of tachyphylaxis. The pressure increases were inversely temperature-dependent, being 4.8 +/- 1.2 mm Hg at 37 degrees C and 22.2 +/- 1.8 mm Hg at 27 degrees C. The vasoconstriction was limited to PGE1 and PGE2. Other prostaglandins tested, PGF2 alpha, PGD2, PGA1, 7-oxo-PGI2 and arachidonic acid, were without any effect at 27 degrees C. Increased serotonin concentrations were found in the effluent after the administration of 1 microgram of PGE1. The pressor response to PGE1 was blocked by 5-HT2 antagonists, ketanserin (2 micrograms) and naftidrofuryl (100 micrograms), while the alpha-adrenoceptor antagonist phentolamine (6.7 micrograms) was without effect. Rapid tachyphylaxis of the development of vasoconstriction was observed after the repeated administration of PGE1 and PGE2. PGE1 (1 microgram) induced desensitization with more than 60 min duration. All the findings suggest that serotonin was liberated in the rat hindlimbs by PGEs.