Pathophysiological analysis for tissue renin-angiotensin-system using Cre-loxP system

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Generation of loxP-franked (floxed) angiotensinogen mice.The conditional angiotensinogen knockout construct was used to generate floxed angiotensinogen mice. Heterozygous mice were bred to generate homozygous mice.Pathophysiological analysis of tissue renin-angiotensin-systemWe examined the role of the renin-angiotensin system (RAS) in the regulation of macula densa cyclooxygenase-2 (COX-2) during altered dietary salt intake using Atg-/- mice. This study demonstrated that COX-2 activity in the macula densa can be regulated by salt intake through a mechanism independent of the RAS, and COX-2 expression is functionally linked to renal cortical N-NOS activity in Atg-/- mice (Nephron Physiol.2006).The effects of altered dietary salt intake on renal endothelial nitric oxide synthase (eNOS) expression were determined in angiotensin type-1a receptor gene knockout (AT1a-/-) mice and Atg-/- mice. This study demonstrated that AT1a receptor-mediated inputs play critical roles in maintaining renal vascular eNOS expression and activity during changes in salt-water balance and systemic BP (J Am Soc Nephrol, 2004, Cell Tissue Res, 2006).We examined the distribution of AT1 receptor-associated protein in nephron segments (Kidney Int,2006).We evaluated the effect of angiotensin II on the pathogenesis of immune mediated colitis using Atg-/-. This study revealed that RAS is involved in the immune system in the colon (Gut,2005).These results demonstrated that an antagonism of the RAS is a potential prophylactic strategy for the treatment of tissue damage.