The vasodepressor function of the kidney: prostaglandin E2 is not the principal vasodepressor lipid of the renal medulla.

摘要

Aim: Whereas prostaglandin E2 has been characterized as the principal vasodepressor lipid, medullipin remains a hypothetical vasodepressor principle of the renal medulla. Representing the first step towards the isolation of medullipin as a pure compound, the aim of the present study was to determine whether or not the known vasodilator and antihypertensive action of prostaglandins play a role in the antihypertensive activity of renal medulla. Methods: A chloroform extract of porcine kidney medulla was fractionated by gradient vacuum liquid chromatography (VLC) and analysed by capillary GC-MS for the presence of prostaglandins (detection limit: 2.2 ppm). The biological activity was determined in spontaneously hypertensive Wistar rats. The particle size of injectable colloids prepared from extract and fractions was controlled by photon correlation spectroscopy. Results: The extract caused a pronounced blood pressure decline (29.6 +/- 6.3/24.9+/- 5.5 mmHg; P = 0.0078; 10 mg kg(-1) body weight; particle size of 143 +/- 18 nm; n = 7) lasting for more than 1 h. The heart rate remained stable, showing only a slightly decrease. All fractions were shown to be devoid of vasodilator prostanoid substances. The VLC procedure allowed the successful separation of endogenous emulsifiers from the active principle. An extract from the renal cortex did not exhibit a similar vasodepressor effect. Conclusion: Prostaglandins are excluded as the blood pressure-lowering active principle of a total lipid kidney medulla extract. The vasodepressor principle is contained in the kidney medulla, but not in the cortex. It can be separated from endogenous emulsifying substances, is chromatographically stable, and is amenable to purification and chemical characterization.