title: Renin-dependent cardiovascular functions and renin-independent blood-brain barrier functions revealed by renin-deficient mice.
abstract: Renin plays a key role in controlling blood pressure through its specific cleavage of angiotensinogen to generate angiotensin I (AI). Although possible existence of the other angiotensin forming enzymes has been discussed to date, its in vivo function remains to be elucidated. To address the contribution of renin, we generated renin knockout mice. Homozygous mutant mice show neither detectable levels of plasma renin activity nor plasma AI, lowered 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 cells of hippocampus and the impaired blood-brain barrier function in angiotensinogen-deficient mice. Surprisingly, however, such brain phenotypes were not observed in renin-deficient mice. Our results demonstrate an indispensable role for renin in the circulating angiotensin generation and in the maintenance of blood pressure, but suggest a dispensable role for renin in the blood-brain barrier function.
authors.affiliation: Center for Tsukuba Advanced Research Alliance, University of Tsukuba, Tsukuba, Ibaraki 305-8577, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Yanai
authors.forename: T
authors.initials: T
authors.lastname: Saito
authors.forename: Y
authors.initials: Y
authors.lastname: Kakinuma
authors.forename: Y
authors.initials: Y
authors.lastname: Kon
authors.forename: K
authors.initials: K
authors.lastname: Hirota
authors.forename: K
authors.initials: K
authors.lastname: Taniguchi-Yanai
authors.forename: N
authors.initials: N
authors.lastname: Nishijo
authors.forename: Y
authors.initials: Y
authors.lastname: Shigematsu
authors.forename: H
authors.initials: H
authors.lastname: Horiguchi
authors.forename: Y
authors.initials: Y
authors.lastname: Kasuya
authors.forename: F
authors.initials: F
authors.lastname: Sugiyama
authors.forename: K i
authors.initials: Ki
authors.lastname: Yagami
authors.forename: K
authors.initials: K
authors.lastname: Murakami
authors.forename: A
authors.initials: A
authors.lastname: Fukamizu
mesh_terms: D000803:Angiotensin I / Q000097:blood*; D000808:Angiotensinogen / Q000097:blood; D000818:Animals; D001794:Blood Pressure; D001812:Blood-Brain Barrier / Q000502:physiology*; D001921:Brain / Q000502:physiology*; D002320:Cardiovascular Physiological Phenomena; D006706:Homeostasis; D006720:Homozygote; D007668:Kidney / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D012083:Renin / Q000172:deficiency*; D012084:Renin-Angiotensin System
chemical_list: D000808:Angiotensinogen; D000803:Angiotensin I; D012083:Renin