Cellular expression of renal, cardiac and pulmonary inducible nitric oxide synthase in double-transgenic mice expressing human renin and angiotensinogen genes.
1. Hypertensive mice expressing the human renin (REN) and angiotensinogen (AGT) genes are used as a model for human hypertension. 2. The aim of the present study was to investigate the cellular expression and distribution of inducible nitric oxide synthase (iNOS) using immunohistochemistry in lung, heart and kidney tissues from a model of human hypertension using male and female double-transgenic (h-Ang 204/1h-Ren6) mice and wild-type C57/BI6J mice as controls. 3. In the kidney, the pattern of iNOS expression in various renal microanatomical regions during hypertension was similar to that of age-matched controls, except in the medullary ascending limb (MAL). In hypertension, iNOS expression was downregulated in the MAL. No significant differences in iNOS expression were seen between control or hypertensive mice in various cardiac microanatomical locations. In the lungs of hypertensive mice, iNOS expression was upregulated in bronchial airway epithelium and bronchial and vascular smooth muscle cells, but downregulated in alveolar macrophages, alveolar septa and pulmonary vascular endothelial cells. Expression of iNOS was similar between male and female mice in the kidney, heart and lungs. 4. In conclusion, iNOS regulation in hypertension is complex and depends on the cell type in which it is expressed and the localization of the cell type in the cardiorenal and pulmonary systems.
Radi
Zaher A
ZA
Drug Safety Research and Development, Pfizer Global Research and Development, St Louis, Misouri 63017, USA. zaher.radi@pfizer.com
Murad
Yahya
Y
D000808:Angiotensinogen / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D006973:Hypertension / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007668:Kidney / Q000201:enzymology / Q000378:metabolism*; D008168:Lung / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology; D052247:Nitric Oxide Synthase Type II / Q000235:genetics* / Q000378:metabolism; D012083:Renin / Q000235:genetics* / Q000378:metabolism
D000808:Angiotensinogen; D052247:Nitric Oxide Synthase Type II; D012083:Renin