ROLES OF VASCULAR ANGIOTENSIN-CONVERTING ENZYME AND CHYMASE IN 2-KIDNEY, ONE-CLIP HYPERTENSIVE HAMSTERS

Background A chymase-dependent angiotensin II-forming pathway is prese nt in human vascular tissues; however, the role, if it plays any, of c hymase in the pathogenesis of hypertension is not known. When investig ating the role of chymase, it is important to recognize marked differe nces in vascular angiotensin II-forming systems among species. We foun d recently that hamsters, like humans, possess the dual angiotensin II -forming system. Objective To analyze the potential involvement of ang iotensin converting enzyme and chymase in the pathogenesis of hyperten sion, and to further characterize the efficiency of angiotensin conver ting enzyme inhibitors and angiotensin II receptor antagonists for the treatment of hypertension. Methods and results The mean arterial pres sure in the two-kidney, one clip hamster model had increased significa ntly 2 weeks after clipping (acute stage), reached a peak after 4 week s, and was sustained at the high level until 32 weeks after clipping ( chronic stage). Plasma renin activity increased markedly during the ac ute stage, but returned to the normal level during the chronic stage. Vascular angiotensin converting enzyme activity during 4-32 weeks afte r clipping was significantly higher than that in the control hamsters, By contrast, vascular chymase was not activated throughout the experi mental period. Administrations of an angiotensin converting enzyme inh ibitor, trandolapril, and an angiotensin II receptor antagonist, CV-11 974, equally lowered the mean arterial pressure during the acute and c hronic stages. Conclusions Vascular angiotensin converting enzyme play s a predominant role in the maintenance of two-kidney, one clip hypert ension in hamsters, which, like humans, possess a dual system of forma tion of angiotensin II, Vascular chymase was not involved in the patho genesis of two-kidney, one clip hypertension in the hamster. (C) 1998 Lippincott-Raven Publishers.