Renin-dependent cardiovascular functions and renin-independent blood-brainbarrier functions revealed by renin-deficient mice

Renin plays a key role in controlling blood pressure through its specific c leavage of angiotensinogen to generate angiotensin I (AI), Although possibl e existence of the other angiotensin forming enzymes has been discussed to date, its in vivo function remains to be elucidated. To address the contrib ution of renin, we generated renin knockout mice. Homozygous mutant mice sh ow neither detectable levels of plasma renin activity nor plasma AI, lowere d blood pressure 20-30 mm Hg less than normal, increased urine and drinking volume, and altered renal morphology as those observed in angiotensinogen- deficient mice. We recently found the decreased density in granular layer c ells of hippocampus and the impaired blood-brain barrier function in angiot ensinogen-deficient mice. Surprisingly, however, such brain phenotypes were not observed in renin-deficient mice. Our results demonstrate an indispens able role for renin in the circulating angiotensin generation and in the ma intenance of blood pressure, but suggest a dispensable role for renin in th e blood-brain barrier function.