Elevated blood pressure following LHRH antagonists in rats

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.