Smith R D, Edgren R A
Contraception. 1982 Apr;25(4):395-403. doi: 10.1016/0010-7824(82)90096-8.
LHRH and three potent antagonistic analogs: z-[Gln1, des-His2,D-Pse6,des-Gly10]-LHRH ethylamide, where D-Pse = threo-D-phenylserine; z-[Gln1,des-His2,D-Phe6,des-Gly10]-LHRH ethylamide; and Boc-[Ser(Bzl)1,des-His2,D-Trp6]-LHRH; were studied for their effects on blood pressure and heart rate in chronically catheterized conscious normotensive and hypertensive rats. All three analogs caused acute increases in blood pressure in normotensive male Sprague-Dawley rats; the z-Gln-Phenylalanine derivative also raised blood pressure in spontaneously hypertensive rats of Kyoto-Wistar origin. LHRH itself had no effect in either normotensive or hypertensive animals. The antagonistic analogs were also associated with acute toxicity. It is concluded that the antagonist analogs of LHRH, unlike LHRH itself, have significant acute cardiovascular effects in rats. Although the mechanism of these effects is not known nor is it known whether they occur in other species, the present data emphasize the need to define further the pharmacological profiles of these potent, biologically active materials.
研究了促性腺激素释放激素（LHRH）及其三种强效拮抗类似物：z-[谷氨酰胺1，去组氨酸2，D-苯基丝氨酸6，去甘氨酸10]-LHRH乙酰胺（其中D-苯基丝氨酸=苏式-D-苯丙氨酸）；z-[谷氨酰胺1，去组氨酸2，D-苯丙氨酸6，去甘氨酸10]-LHRH乙酰胺；以及Boc-[丝氨酸（苄酯）1，去组氨酸2，D-色氨酸6]-LHRH对慢性插管清醒正常血压和高血压大鼠血压和心率的影响。所有这三种类似物均使正常血压的雄性斯普拉格-道利大鼠血压急性升高；z-谷氨酰胺-苯丙氨酸衍生物也使京都-威斯塔自发性高血压大鼠血压升高。LHRH本身对正常血压或高血压动物均无影响。这些拮抗类似物还具有急性毒性。得出的结论是，与LHRH本身不同，LHRH的拮抗类似物在大鼠中具有显著的急性心血管作用。尽管这些作用的机制尚不清楚，也不知道它们是否在其他物种中发生，但目前的数据强调需要进一步明确这些强效生物活性物质的药理学特征。
