Hypertensive mice that express the human renin and
angiotensinogen genes are used as a model for human hypertension
because they develop hypertension secondary to increased
renin-angiotensin system activity. Our study investigated the cellular
localization and distribution of COX-1, COX-2, mPGES-1, and
mPGES-2 in organ tissues from a mouse model of human
hypertension.
Male (n=15) and female (n=15) double transgenic mice (h-Ang 204/1 h-Ren 9)
were used in the study. Lung, kidney, and heart tissues were obtained from mice
at necropsy and fixed in 10% neutral buffered formalin followed by embedding in paraffin wax. Cut
sections were stained immunohistochemically with antibodies to COX-1, COX-2,
mPGES-1, and mPGES-2 and analyzed by light microscopy. Renal expression of
COX-1 was the highest in the distal convoluted tubules, cortical collecting ducts, and
medullary collecting ducts; while proximal convoluted tubules lacked COX-1
expression. Bronchial and bronchiolar epithelial cells, alveolar macrophages, and cardiac
vascular endothelial cells also had strong COX-1 expression, with other renal, pulmonary,
or cardiac microanatomic locations having mild-to-moderate expression. mPGES-2
expression was strong in the bronchial and bronchiolar epithelial cells, mild to moderate
in various renal microanatomic locations, and absent in cardiac tissues. COX-2 expression
was strong in the proximal and distal convoluted tubules, alveolar macrophages, and
bronchial and bronchiolar epithelial cells. Marked mPGES-1 was present only in
bronchial and bronchiolar epithelial cells; while mild-to-moderate expression was
present in other pulmonary, renal, or cardiac microanatomic locations. Expression
of these molecules was similar between males and females.
Our work suggests that in hypertensive mice, there are (a) significant microanatomic
variations in the pulmonary, renal, and cardiac distribution and cellular localization
of COX-1, COX-2, mPGES-1, and mPGES-2, and (b) no differences in expression
between genders.