Effect of delapril on the vascular angiotensin II release in isolated hind legs of the spontaneously hypertensive rat: evidence for potential relevance of vascular angiotensin II to the maintenance of hypertension.
1. In view of a recent interesting hypothesis that the vascular renin-angiotensin system (RAS) plays an important role in the maintenance of hypertension, we examined the effect of delapril (DP), a newly developed angiotensin converting enzyme inhibitor (ACEI), on angiotensin II (Ang II) release from isolated perfused hind legs of spontaneously hypertensive rats (SHR) in comparison with normotensive rats of Wistar-Kyoto strain (WKY). 2. Male SHR and WKY were given DP orally (10 mg/kg per day) for 2 weeks. Isolated hind legs of these rats were perfused with angiotensinogen-free Krebs-Ringer solution, and Ang II released into the perfusate was determined directly by extraction with Sep-Pak C18 cartridges connected to the perfusion system. 3. Delapril produced a sustained antihypertensive action in SHR but not in WKY. The spontaneous release of Ang II in SHR was 112.9 +/- 17.6 pg during the first 30 min of perfusion, which was somewhat greater than that in WKY (96.5 +/- 9.8 pg). An active metabolite of DP, delapril diacid (DPD), when added to the perfusion medium, suppressed the Ang II release in a dose-dependent manner in the two strains. Oral pretreatment of DP for 2 weeks suppressed the Ang II release by 60% in WKY and more pronouncedly by 73% in SHR. 4. These results suggest the presence of a functional RAS in vascular tissues which contributes to the maintenance of vascular tone of SHR, and that ACEI including DP exerts their antihypertensive effect through inhibition of vascular Ang II release in this animal model of human hypertension.
Mizuno
K
K
Third Department of Internal Medicine, Fukushima Medical College, Japan.
Tani
M
M
Niimura
S
S
Fukuchi
S
S
D000804:Angiotensin II / Q000097:blood / Q000378:metabolism*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000378:metabolism; D006973:Hypertension / Q000378:metabolism*; D007189:Indans / Q000008:administration & dosage / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012084:Renin-Angiotensin System / Q000502:physiology
D000806:Angiotensin-Converting Enzyme Inhibitors; D007189:Indans; D000804:Angiotensin II; C047759:delapril