Renal and vascular glutathione S-transferase mu is not affected by pharmacological intervention to reduce systolic blood pressure.
BACKGROUND
Our previous studies demonstrated reduced rat glutathione S-transferase mu 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.


CONCLUSIONS
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.
Koh-Tan
Han Hui Caline
HH
Division of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow G12 8TA, UK.
Graham
Delyth
D
Hamilton
Carlene A
CA
Nicoll
Gavin
G
Fields
Laura
L
McBride
Martin W
MW
Young
Barbara
B
Dominiczak
Anna F
AF
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D005982:Glutathione Transferase / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D006801:Humans; D006852:Hydrochlorothiazide / Q000031:analogs & derivatives / Q000627:therapeutic use; D006973:Hypertension / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D007093:Imidazoles / Q000627:therapeutic use; D007668:Kidney / Q000201:enzymology*; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013481:Superoxides / Q000378:metabolism; D013599:Systole / Q000187:drug effects*; D013777:Tetrazoles / Q000627:therapeutic use
D000111:Acetylcysteine; D005982:Glutathione Transferase; D006852:Hydrochlorothiazide; D007093:Imidazoles; D013481:Superoxides; D013777:Tetrazoles; C437965:olmesartan; C412602:glutathione S-transferase Mu 2; C009732:buthiazide