Roles of vascular angiotensin converting enzyme and chymase in two-kidney, one clip hypertensive hamsters.
BACKGROUND
A chymase-dependent angiotensin II-forming pathway is present in human vascular tissues; however, the role, if it plays any, of chymase in the pathogenesis of hypertension is not known. When investigating the role of chymase, it is important to recognize marked differences in vascular angiotensin II-forming systems among species. We found recently that hamsters, like humans, possess the dual angiotensin II-forming system.


OBJECTIVE
To analyze the potential involvement of angiotensin converting enzyme and chymase in the pathogenesis of hypertension, and to further characterize the efficiency of angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists for the treatment of hypertension.


RESULTS
The mean arterial pressure in the two-kidney, one clip hamster model had increased significantly 2 weeks after clipping (acute stage), reached a peak after 4 weeks, and was sustained at the high level until 32 weeks after clipping (chronic stage). Plasma renin activity increased markedly during the acute stage, but returned to the normal level during the chronic stage. Vascular angiotensin converting enzyme activity during 4-32 weeks after clipping was significantly higher than that in the control hamsters. By contrast, vascular chymase was not activated throughout the experimental period. Administrations of an angiotensin converting enzyme inhibitor, trandolapril, and an angiotensin II receptor antagonist, CV-11974, equally lowered the mean arterial pressure during the acute and chronic stages.


CONCLUSIONS
Vascular angiotensin converting enzyme plays a predominant role in the maintenance of two-kidney, one clip hypertension in hamsters, which, like humans, possess a dual system of formation of angiotensin II. Vascular chymase was not involved in the pathogenesis of two-kidney, one clip hypertension in the hamster.
Jin
D
D
Department of Pharmacology, Osaka Medical College, Takatsuki, Japan.
Takai
S
S
Shiota
N
N
Miyazaki
M
M
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use; D001011:Aorta / Q000201:enzymology* / Q000503:physiopathology; D001562:Benzimidazoles / Q000494:pharmacology / Q000627:therapeutic use; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D053818:Chymases; D006224:Cricetinae; D006801:Humans; D006978:Hypertension, Renovascular / Q000097:blood / Q000188:drug therapy / Q000201:enzymology*; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D012083:Renin / Q000097:blood; D012697:Serine Endopeptidases / Q000378:metabolism*; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D007211:Indoles; D013777:Tetrazoles; C052035:trandolapril; D007703:Peptidyl-Dipeptidase A; D012697:Serine Endopeptidases; D053818:Chymases; D012083:Renin; C081643:candesartan