Sirén A L, Karppanen H
Prostaglandins. 1980 Aug;20(2):285-96. doi: 10.1016/s0090-6980(80)80047-5.
The centrally acting antihypertensive drug clonidine has been found to stimulate the synthesis of PGF2 alpha in the brain. Centrally administered PGF2 alpha, in turn, induces rises of blood pressure and heart rate. We therefore studied the influence of inhibitors of prostaglandin (PG) synthesis on the cardiovascular effects of clonidine in urethane-anaesthetised rats. Pretreatment with indomethacin or paracetamol (100 micrograms/rat into the fourth cerebral ventricle) antagonised the central hypotensive effect of clonidine (0.125-16.0 micrograms/rat into the fourth cerebral ventricle). The bradycardic effect of centrally administered clonidine was, however, enhanced by pretreatment with paracetamol but not influenced by indomethacin pretreatment. Sodium meclofenamate (100 micrograms/rat into the fourth cerebral ventricle) did not significantly affect the clonidine-induced changes in blood pressure and heart rate. These results suggest that the clonidine-induced hypotension on one hand and bradycardia on the other hand may be mediated by partly different mechanisms. An interference of the formation of PGF2 alpha with the cardiovascular effects of clonidine cannot be completely excluded since paracetamol pretreatment potentiated the bradycardic effect of clonidine. However, inhibitors of PG synthesis did not enhance but antagonised the hypotensive effect of clonidine. Therefore it is likely that the synthesis of PGF2 alpha does not interfere with the hypotensive effect of clonidine. Moreover, the antagonism of the hypotensive effect by inhibitors of PG synthesis suggests that some hypotensive metabolite of arachidonic acid in the brain could be involved in the central hypotensive effect of clonidine.
中枢性抗高血压药物可乐定已被发现可刺激大脑中前列腺素F2α（PGF2α）的合成。反过来，经中枢给予PGF2α会导致血压升高和心率加快。因此，我们研究了前列腺素（PG）合成抑制剂对可乐定在乌拉坦麻醉大鼠中的心血管效应的影响。用吲哚美辛或对乙酰氨基酚（每只大鼠100微克注入第四脑室）预处理可拮抗可乐定（每只大鼠0.125 - 16.0微克注入第四脑室）的中枢降压作用。然而，对乙酰氨基酚预处理增强了经中枢给予可乐定的减慢心率作用，而吲哚美辛预处理对其无影响。甲氯芬那酸钠（每只大鼠100微克注入第四脑室）对可乐定引起的血压和心率变化无显著影响。这些结果表明，可乐定引起的低血压和减慢心率可能由部分不同的机制介导。由于对乙酰氨基酚预处理增强了可乐定的减慢心率作用，所以不能完全排除PGF2α的形成对可乐定心血管效应的干扰。然而，PG合成抑制剂并未增强而是拮抗了可乐定的降压作用。因此，PGF2α的合成可能不会干扰可乐定的降压作用。此外，PG合成抑制剂对降压作用的拮抗表明，大脑中花生四烯酸的某些降压代谢产物可能参与了可乐定的中枢降压作用。
