Alterations in serotonergic receptor expression in experimental vein grafts.
Rabbit external jugular veins, normally unresponsive to serotonin (5-HT), develop a constrictive response when grafted into the arterial circulation. The mechanisms responsible for this alteration were examined in this study. The right external jugular vein was grafted into the right carotid artery in 37 New Zealand white rabbits. The vein grafts were harvested at 3, 7, 9, 14, and 28 days after operation; contralateral external jugular veins were harvested at 9 days in six animals. Rings of these vessels were mounted under isometric tension, and dose-response curves to 5-HT were obtained. None of the grafts harvested at day 3 responded to 5-HT. All the grafts harvested from day 7 through day 28 constricted to 5-HT. The maximal response increased from 258 +/- 30 mg at 7 days to 734 +/- 108 mg at 28 days. No change occurred in the sensitivity to 5-HT with time. The increase in maximal response was paralleled by a linear increase in percent intimal area (intimal area/intimal + media areas) from 11.6% +/- 2.1% at 3 days to 48.7% +/- 1.9% at 28 days. Preincubation with ketanserin, a 5-HT2 and alpha 1-adrenergic antagonist, produced a concentration-dependent rightward shift in the 5-HT dose-response curve. The median effective dose for 5-HT increased progressively from 1.9 +/- 0.3 x 10(-6) mol/L (in the absence of ketanserin) to 6.1 +/- 1.7 x 10(-5) mol/L (ketanserin 8 x 10(-7) mol/L; p less than 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)
Radic, ZS; O'Donohoe, MK; Schwartz, LB; Stein, AD; Mikat, EM; McCann, RL; Hagen, PO
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