U-46619 INDUCES DIFFERENT BLOOD-PRESSURE EFFECTS IN MALE AND FEMALE SPONTANEOUSLY HYPERTENSIVE RATS (SHR)

The effect of U 46619 (5 mug/kg i.v.) alone or in combination with ace tylsalicylic acid (ASA)(100 mg/kg po.) on mean arterial blood pressure (MABP) was investigated in male and female spontaneously hypertensive rats (SHR). In male SHR, a significant increase of MABP was observed 1 min after administration of U 46619. Pretreatment of male SHR with A SA delayed the increase of MABP after intravenous injection of U 46619 compared to U 46619 alone. Whereas in control animals the elevated MA BP returned to baseline values 5 min after intravenous application of U 46619, the MABP of ASA-pretreated male SHR remained significantly in creased by about 30 mmHg. In contrast, the MABP of female SHR did not respond to U 46619 alone or to the combination of U 46619 and ASA. Sex differences were further shown by the vascular formation of thromboxa ne B2 (TXB2). Whereas in male SHR the vascular formation of TXB2 was i ncreased by U 46619, the TXB2 formation of female SHR was decreased. T he vascular formation of 6-keto-PGF1alpha of male and female SHR was n ot influenced by U 46619 alone or a combination of U 46619 and ASA. In conclusion, our results demonstrate that the blood pressure of SHR re spond differently to the TXA2 mimetic U 46619 in the two sexes. Furthe rmore, by modulating blood pressure response to TXA2, vasoactive prost anoids may be significantly involved in the maintenance of hypertensio n with male SHR.