Effects of des-aspartate-angiotensin I on neointima growth and cardiovascular hypertrophy.
The in vitro anti-hypertrophic and hyperplastic actions of des-aspartate-angiotensin I (DAA-I) on cultured cardiovascular cells have been demonstrated in earlier experiments. The present study investigated its effects on the development of neointima in balloon catheter-injured carotid artery of the Sprague-Dawley (SD) rat and the development of cardiovascular hypertrophy in the spontaneously hypertensive rat. Treatment with i.v. DAA-I for 14 days post-injury dose-dependently attenuated the development of neointima. The maximum effect was obtained at 34 pmol/kg/day. The data support the possibility that endogenous angiotensins could inhibit neointima growth. This opens up avenues for their therapeutic elevation in combating neointima-related restenosis of which current drugs are not fully effective in suppressing. Five-week-old pre-hypertensive SHR, when orally administered with a dose of 769 nmol/kg/day DAA-I for a duration of 47 weeks, showed significant reduction in the development of cardiac and vascular hypertrophy compared to the untreated controls. Similar treatment with DAA-I had no effect on the Wistar Kyoto rats. The present findings support the contention that, besides angiotensin II, other endogenous angiotensins are also involved in the regulation and/or pathophysiology of the cardiovascular system.
Kwoon
Sim Meng
SM
Department of Pharmacology, Faculty of Medicine, National University of Singapore, Building MD2, 18 Medical Drive, 117597, Singapore. phcsimmk@nus.edu.sg
Ru
Tang Feng
TF
Guang
Xu Xiao
XX
D000803:Angiotensin I / Q000494:pharmacology / Q000502:physiology; D000805:Angiotensin III / Q000502:physiology / Q000627:therapeutic use*; D000818:Animals; D001157:Arterial Occlusive Diseases / Q000188:drug therapy* / Q000473:pathology; D001161:Arteriosclerosis / Q000209:etiology; D006332:Cardiomegaly / Q000188:drug therapy*; D002312:Cardiomyopathy, Hypertrophic / Q000209:etiology; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000209:etiology; D007275:Injections, Intravenous; D008297:Male; D051381:Rats; D017539:Tunica Intima / Q000187:drug effects* / Q000473:pathology
D000805:Angiotensin III; D000803:Angiotensin I