U 46619 induces different blood pressure effects in male and female spontaneously hypertensive rats (SHR).
The effect of U 46619 (5 micrograms/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 B2 (TXB2). Whereas in male SHR the vascular formation of TXB2 was increased by U 46619, the TXB2 formation of female SHR was decreased. The vascular formation of 6-keto-PGF1 alpha 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 TXA2 mimetic U 46619 in the two sexes. Furthermore, by modulating blood pressure response to TXA2, vasoactive prostanoids may be significantly involved in the maintenance of hypertension with male SHR.
Schirner
M
M
Institute of Pharmacology, School of Medicine, University of Halle, Federal Republic of Germany.
Taube
C
C
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000284:Administration, Oral; D000818:Animals; D001011:Aorta / Q000187:drug effects; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D004357:Drug Synergism; D005260:Female; D007275:Injections, Intravenous; D008297:Male; D011450:Prostaglandin Endoperoxides, Synthetic / Q000008:administration & dosage / Q000494:pharmacology*; D011460:Prostaglandins F / Q000096:biosynthesis; D051381:Rats; D011918:Rats, Inbred SHR; D013929:Thromboxane B2 / Q000096:biosynthesis; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology*
D011450:Prostaglandin Endoperoxides, Synthetic; D011460:Prostaglandins F; D014662:Vasoconstrictor Agents; D013929:Thromboxane B2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D001241:Aspirin; C100006:prostaglandin F1