Role of chymase-dependent angiotensin II formation in regulating blood pressure in spontaneously hypertensive rats.
Vascular smooth muscle cells in spontaneously hypertensive rats (SHR) express angiotensin II-forming chymase (rat vascular chymase [RVCH]), which may contribute to blood pressure regulation. In this study, we studied whether chymase-dependent angiotensin II formation contributes to the regulation of blood pressure in SHR. The systolic blood pressure in 16-week-old Wistar-Kyoto (WKY) rats was 113 +/- 9 mmHg, compared to 172 +/- 3 mmHg in SHR. Using synthetic substrates for measuring angiotensin-converting enzyme (ACE) and chymase activities, it was found that both ACE and chymase activities in extracts from SHR aortas were significantly higher than in those from WKY rat aortas. Using angiotensin I as a substrate, angiotensin II formation in SHR was found to be significantly higher than that in WKY rats, and its formation was completely suppressed by an ACE inhibitor, but not by a chymase inhibitor. RVCH mRNA expression could not be detected in aorta extracts from either WKY rats or SHR. In carotid arteries isolated from WKY rats and SHR, angiotensin I-induced vasoconstriction was completely suppressed by an ACE inhibitor, but not by a chymase inhibitor. Angiotensin I-induced pressor responses in both WKY rats and SHR were also completely inhibited by an ACE inhibitor, but they were not affected by a chymase inhibitor. In SHR, an ACE inhibitor and an angiotensin II receptor blocker showed equipotent hypotensive effects, but a chymase inhibitor did not have a hypotensive effect. These results indicated that chymase-dependent angiotensin II did not regulate blood pressure in SHR in the present study.
Kirimura
Kazuyoshi
K
Department of Pharmacology, Osaka Medical College, Takatsuki, Japan.
Takai
Shinji
S
Jin
Denan
D
Muramatsu
Michiko
M
Kishi
Kanta
K
Yoshikawa
Katsuhiro
K
Nakabayashi
Mika
M
Mino
Yoshiki
Y
Miyazaki
Mizuo
M
D000803:Angiotensin I / Q000378:metabolism; D000804:Angiotensin II / Q000096:biosynthesis / Q000378:metabolism*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000201:enzymology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D001835:Body Weight; D053818:Chymases; D015971:Gene Expression Regulation, Enzymologic; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000201:enzymology; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D014661:Vasoconstriction / Q000502:physiology
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D012333:RNA, Messenger; D000804:Angiotensin II; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; D012697:Serine Endopeptidases; D053818:Chymases