Abstract
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.
Highlights
The renin-angiotensin-aldosterone system (RAAS) plays an important role in the control of cardiovascular and renal homeostasis by regulating vascular tone, blood pressure (BP), and fluid volume [1, 2]
Angiotensin II (Ang II) is a physiologically active component of the RAAS, produced via an enzymatic cascade that begins with angiotensinogen (AGT) cleaving renin (REN) to form angiotensin I (Ang I), which is cleaved by the angiotensin converting enzyme (ACE) to form Ang II [3]
Strong diffuse cytoplasmic COX-1 expression occurred in the distal convoluted tubules (DCT), cortical collecting ducts, and medullary collecting ducts, while proximal convoluted tubules (PCT) lacked COX-1 expression (see Figure 1(a) and Table 1)
Summary
The renin-angiotensin-aldosterone system (RAAS) plays an important role in the control of cardiovascular and renal homeostasis by regulating vascular tone, blood pressure (BP), and fluid volume [1, 2]. Mediators of Inflammation double transgenic line (Ang 204/1 Ren 9), which produces a mean arterial BP 40mmHg higher than background mice (C57Bl/6J) that lack the human genes [2]. There is increasing evidence that suggests a RAAS may reside within several organs or tissues, including kidney, lung, heart, and vascular smoothmuscle cells (SMC), where it is believed to act in a functionally independent paracrine/autocrine fashion [6]. Using immunohistochemistry, we investigated the microanatomic location and cellular expression of COX-1, COX-2, mPGES-1, mPGES-2 in kidney, lung, and heart tissues obtained from renin-angiotensingen transgenic mice. This study is the first to report on the pulmonary and Cardiorenal microanatomic expression of these molecules in this animal model for human hypertension
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