Significant role of the increase in renin-angiotensin system in cardiac hypertrophy and renal glomerular sclerosis in double transgenic tsukuba hypertensive mice carrying both human renin and angiotensinogen genes.
Tsukuba hypertensive mice (THM) are a hypertensive model prepared by mating a transgenic mice with human renin gene and a transgenic mice with human angiotensinogen gene. In the present study, we examined effects of renin-angiotensin system (RAS) on cardiac hypertrophy and renal disorders using Tsukuba hypertensive mice. While THM showed an increase of about 30 mmHg in systolic pressure compared to C57BL/6 mice employed as normal control animals, the increase in blood pressure was not observed in the mice to which either gene was transferred. Urinary volume, water intake volume, urinary albumin excretion, heart to body weight ratio and renal glomerular sclerosis index increased significantly in THM, but none of these parameters showed a significant difference from the C57 mice when they were examined in mice to which either of the genes was transferred. In contrast, when lisinopril was administered to THM, all the parameters decreased significantly without lowering the systolic pressure. From these findings, it was demonstrated that RAS was playing a significant role in cardiac hypertrophy and renal disorders of THM and that lisinopril had inhibitory effects on cardiac hypertrophy and renal glomerular sclerosis by inhibiting RAS.
Kai
T
T
First Department of Internal Medicine, Kinki University School of Medicine, Osaka-Sayama, Japan.
Kino
H
H
Sugimura
K
K
Shimada
S
S
Kurooka
A
A
Akamatsu
K
K
Takenaka
T
T
Fukamizu
A
A
Murakami
K
K
Ishikawa
K
K
Katori
R
R
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000808:Angiotensinogen / Q000235:genetics; D000818:Animals; D006332:Cardiomegaly / Q000473:pathology / Q000503:physiopathology*; D005923:Glomerulosclerosis, Focal Segmental / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D006973:Hypertension / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D017706:Lisinopril / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic / Q000235:genetics; D012083:Renin / Q000235:genetics; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000808:Angiotensinogen; D017706:Lisinopril; D012083:Renin