Local generation and release of angiotensin II in peripheral vascular tissue.
Isolated rat hindlegs were perfused with Krebs-Ringer solution, and immunoreactive angiotensin II (irAng II) released into the perfusate was directly determined using a Sep-Pak C18 cartridge connected to the perfusion system. High performance liquid chromatography clearly demonstrated the presence of angiotensin I (Ang I), angiotensin II (Ang II), and a small amount of angiotensin III. The spontaneous release of irAng II was as high as about 600 pg/30 min, which was stable up to 3 hours. Captopril added to the perfusion medium (10(-9) to 10(-6) M) suppressed irAng II release in a dose-dependent manner (p less than 0.001), and it (10(-6)M) caused a reciprocal increase of irAng I release (p less than 0.05). Oral pretreatment of captopril (50 mg/kg/day) for 1 week suppressed the irAng II release by 31% (p less than 0.02). The same treatment with SA 446, a highly lipophilic angiotensin converting enzyme inhibitor, inhibited the irAng II release by 63% (p less than 0.001). On the other hand, the two inhibitors suppressed the plasma irAng II to very similar extents. Pretreatment with SA 446 plus nephrectomy did not cause any further change in irAng II release as compared with that with SA 446 alone. These results provide direct proof for local generation and subsequent secretion of Ang II by peripheral vascular tissue.
Mizuno
K
K
Department of Biochemistry and Hypertension, Specialized Center of Research (SCOR), Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
Nakamaru
M
M
Higashimori
K
K
Inagami
T
T
D015097:3-Mercaptopropionic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D002216:Captopril / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D006614:Hindlimb; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D012084:Renin-Angiotensin System; D053778:Thiazolidines
D000806:Angiotensin-Converting Enzyme Inhibitors; D053778:Thiazolidines; D000804:Angiotensin II; D002216:Captopril; D015097:3-Mercaptopropionic Acid; C033437:rentiapril