Transgenic mice expressing the human angiotensinogen gene had normal baseline blood pressure, but infusion of purified human renin caused a transient increase in blood pressure of approximately 30 mm Hg.
Does infusion of human renin increase blood pressure in transgenic mice overexpressing the human angiotensinogen gene?
Transgenic mice overexpressing human angiotensinogen maintain normal baseline blood pressure but exhibit a significant transient hypertensive response to human renin, providing an animal model for studying the pathogenesis of essential hypertension.
The renin-angiotensin system is a major determinant of arterial pressure and volume homeostasis in mammals through the actions of angiotensin II, the proteolytic digestion product of angiotensinogen. Molecular genetic studies in several human populations have revealed genetic linkage between the angiotensinogen gene and both hypertension and increased plasma angiotensinogen. Transgenic mice were generated with a human angiotensinogen genomic clone to develop an animal model to examine tissue- and cell-specific expression of the gene and to determine if overexpression of angiotensinogen results in hypertension. Human angiotensinogen mRNA was expressed in transgenic mouse liver, kidney, heart, adrenal gland, ovary, brain, and white and brown adipose tissue and, in kidney, was exclusively localized to epithelial cells of the proximal convoluted tubules. Plasma levels of human angiotensinogen were approximately 150-fold higher in transgenic mice than that found normally in human plasma. The blood pressure of mice bearing the human angiotensinogen gene was normal but infusion of a single bolus dose of purified human renin resulted in a transient increase in blood pressure of approximately 30 mm Hg within 2 min. These results suggest that abnormalities in the angiotensinogen gene resulting in increased circulating levels of angiotensinogen could potentially contribute in part to the pathogenesis of essential hypertension.
Yang et al. (Thu,) conducted a other in Hypertension. Human angiotensinogen genomic clone was evaluated on Blood pressure response to purified human renin infusion. Transgenic mice expressing the human angiotensinogen gene had normal baseline blood pressure, but infusion of purified human renin caused a transient increase in blood pressure of approximately 30 mm Hg.