降压系统与犬类糖皮质激素过量所致高血压有关。

Depressor systems contribute to hypertension induced by glucocorticoid excess in dogs.

作者信息

Nakamoto H, Suzuki H, Kageyama Y, Murakami M, Ohishi A, Naitoh M, Ichihara A, Saruta T

机构信息

Department of Internal Medicine, Keio University, Tokyo, Japan.

出版信息

J Hypertens. 1992 Jun;10(6):561-9. doi: 10.1097/00004872-199206000-00009.

DOI:10.1097/00004872-199206000-00009

PMID:1320077

Abstract

OBJECTIVE

The aim of this study was to investigate the role of depressor systems in glucocorticoid-induced hypertension.

METHODS

The serial changes in cardiorenal hemodynamics, urinary excretions of kallikrein and prostaglandins (PGE2 and the prostacyclin derivative 6-keto-PGF1 alpha) before, and during the administration of both low and high doses of dexamethasone (9 alpha-fluoro-16 alpha-methylprednisolone) and after the cessation of dexamethasone were examined in conscious trained dogs. In addition, pressor responses to prostaglandin, bradykinin, bradykinin antagonist and indomethacin were studied during the administration of dexamethasone.

RESULTS

High-dose dexamethasone induced a significant elevation in mean arterial pressure (MAP) that was accompanied by a significant reduction in the urinary excretion of kallikrein, PGE2 and 6-keto-PGF1 alpha. In contrast, low-dose dexamethasone treatment had no significant effect upon MAP but induced a transient elevation in the urinary excretion of kallikrein, PGE2 and 6-keto-PGF1 alpha. Furthermore, additional oral administration of indomethacin produced a significant elevation in MAP in dogs treated with low-dose dexamethasone; but did not affect the hemodynamics of animals with high-dose dexamethasone. Whilst i.v. administration of either bradykinin or prostacyclin induced a significant reduction in MAP in high-dose but not low-dose dexamethasone-treated dogs, administration of a competitive bradykinin antagonist, D-Arg-[Hyp3, Thi5,8, D-Phe7]-bradykinin induced a significant elevation in MAP in low-dose but not high-dose dexamethasone-treated dogs.

CONCLUSION

Depressor systems play an important role in regulation of blood pressure in glucocorticoid-treated dogs.

摘要

目的

本研究旨在探讨降压系统在糖皮质激素诱导的高血压中的作用。

方法

在清醒的训练犬中，检测低剂量和高剂量地塞米松（9α-氟-16α-甲基泼尼松龙）给药前、给药期间及停药后心脏和肾脏血流动力学的系列变化，以及激肽释放酶、前列腺素（PGE2和前列环素衍生物6-酮-PGF1α）的尿排泄情况。此外，研究地塞米松给药期间对前列腺素、缓激肽、缓激肽拮抗剂和吲哚美辛的升压反应。

结果

高剂量地塞米松导致平均动脉压（MAP）显著升高，同时激肽释放酶、PGE2和6-酮-PGF1α的尿排泄显著减少。相比之下，低剂量地塞米松治疗对MAP无显著影响，但导致激肽释放酶、PGE2和6-酮-PGF1α的尿排泄短暂升高。此外，额外口服吲哚美辛使低剂量地塞米松治疗的犬的MAP显著升高；但不影响高剂量地塞米松治疗动物的血流动力学。静脉注射缓激肽或前列环素可使高剂量但非低剂量地塞米松治疗的犬的MAP显著降低，而竞争性缓激肽拮抗剂D-Arg-[Hyp3, Thi5,8, D-Phe7]-缓激肽可使低剂量但非高剂量地塞米松治疗的犬的MAP显著升高。