U 46619 induces different blood pressure effects in male and female spontaneously hypertensive rats (SHR).

Abstract The effect of U 46619 (5 μg/kg i.v.) alone or in combination with acetylsalicylic 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 ASA delayed the increase of MABP after intravenous injection of U 46619 compared to U 46619 alone. Whereas in control animals the elevated MABP returned to baseline values 5 min after intravenous application of U 46619, the MABP of ASA-pretreated male SHR remained significantly increased 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 thromboxane B 2 (TXB 2 ). Whereas in male SHR the vascular formation of TXB 2 was increased by U 46619, the TXB 2 formation of female SHR was decreased. The vascular formation of 6-keto-PGF 1α of male and female SHR was not influenced by U 46619 alone or a combination of U 46619 and ASA. In conclusion, our results demonstrate that the blood pressure of SHR respond differently to the TXA 2 mimetic U 46619 in the two sexes. Furthermore, by modulating blood pressure response to TXA 2 , vasoactive prostanoids may be significantly involved in the maintenance of hypertension with male SHR.