Species-Specific Kinetics of Mouse Renin Contribute to Maintenance of Normal Blood Pressure in Transgenic Mice with Overexpressed Human Angiotensinogen

Abstract

Angiotensinogen, the precursor of a vasoactive octapeptide angiotensin II, is the only known natural substrate of renin, and its reaction exhibits strict species specificity and is the rate-limiting step in the renin-angiotensin system that controls the blood pressure. We measured blood pressure and heart rate of the transgenic mice with overproduced human angiotensinogen, and showed no significant difference in these parameters between transgenic and nontransgenic mice. We also provided evidence that mouse renin could not cleave human angiotensinogen, indicating a lack of angiotensin production from the human substrate. These results suggested that the blood pressure of transgenic mice is normally maintained, probably due to the inability of mouse renin to release angiotensin from the transgene products.