Renal and vascular glutathione S-transferase mu is not affected by pharmacological intervention to reduce systolic blood pressure

Koh-Tan, H., Graham, D. , Hamilton, C., Nicoll, G., Fields, L., McBride, M. , Young, B., Young, B. and Dominiczak, A. (2009) Renal and vascular glutathione S-transferase mu is not affected by pharmacological intervention to reduce systolic blood pressure. Journal of Hypertension, 27(8), pp. 1575-1584. (doi: 10.1097/HJH.0b013e32832cc5a1)

Abstract

Background Our previous studies demonstrated reduced rat glutathione S-transferase m type 1 (Gstm1) expression in stroke-prone spontaneously hypertensive rats (SHRSPs), when compared with the normotensive Wistar-Kyoto rat. Methods This study investigated the effects of angiotensin II type 1 receptor blocker (ARB) and a diuretic/vasodilator combination on the expression levels of rat Gstm1 and other Gstm isoforms. Results Antihypertensive treatments of young and mature SHRSPs with an ARB and a diuretic/vasodilator combination improved SBP but did not affect the expression levels of Gstm1. Although Gstm1 is a member of a family of highly homologous genes, with the exception of Gstm2, there was no evidence for compensatory increase in expression of other Gstm isoforms. In contrast, we observed reduced expression of several other Gstm isoforms in untreated SHRSPs. Untreated SHRSPs demonstrated increased renal and vascular oxidative stress, both of which were not significantly affected by the antihypertensive treatments. Untreated SHRSPs scored significantly higher when assessed for renal histopathological damage, and this was improved by antihypertensive treatments. Conclusion These results suggest that reduced Gstm1 expression in SHRSPs is due to strain-dependent genetic abnormalities, playing a causative role in the development of hypertension, probably through oxidative stress pathway. Renal changes occur as a consequence of increased blood pressure and can be improved when treated with antihypertensive drugs. In silico comparative genome analysis combined with expression studies in rat and human vascular tissue revealed that there are possible four human homologues (GSTM1, GSTM2, GSTM4 and GSTM5) for rat Gstm1.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Young, Dr Barbara and Graham, Dr Delyth and Burns, Mrs Beth and McBride, Dr Martin and Hamilton, Dr Carlene and Dominiczak, Professor Anna and Koh-Tan, Dr Caline
• Authors: Koh-Tan, H., Graham, D., Hamilton, C., Nicoll, G., Fields, L., McBride, M., Young, B., Young, B., and Dominiczak, A.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences
• Journal Name: Journal of Hypertension
• Publisher: Lippincott Williams & Wilkins
• ISSN: 0263-6352