Nephrectomy, converting enzyme inhibition, and angiotensin peptides.
To determine the contribution of kidney-derived renin and angiotensin converting enzyme to circulating and tissue levels of angiotensin peptides, we measured angiotensin (Ang)-(1-7), Ang II, Ang-(1-9), and Ang I in plasma, kidney, lung, heart, aorta, brown adipose tissue, adrenal, pituitary, and brain of five groups of male Sprague-Dawley rats: control rats, rats given the converting enzyme inhibitor ramipril (10 mg/kg), rats nephrectomized 24 hours, rats nephrectomized 48 hours, and rats nephrectomized 48 hours and given ramipril. Plasma and tissues, apart from adrenal, showed a 63% to 98% reduction in Ang II, the ratio of Ang II to Ang I, or both after ramipril administration, indicating a major role for converting enzyme in Ang II formation. Nephrectomy caused a more than 95% decrease in plasma renin levels and a fourfold to eightfold increase in plasma angiotensinogen levels. Apart from plasma and brain, tissues showed a 59% to 78% decrease in Ang II levels after nephrectomy, indicating a major role for kidney-derived renin in Ang II formation. The persistence of Ang II in plasma and tissues of anephric rats indicates that Ang II may be formed by a process independent of kidney-derived renin; this process may be amplified by the increased plasma angiotensinogen levels that accompany nephrectomy. For lung, adrenal, and aorta, Ang II levels showed a further decrease when nephrectomized rats were given ramipril. However, for plasma and the other tissues, ramipril produced little or no decrease in Ang II levels of anephric rats, suggesting that Ang II may be formed by a pathway independent of converting enzyme. Such a pathway may involve the direct formation of Ang II from angiotensinogen by a non-renin-like enzyme.
Campbell
D J
DJ
St Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia.
Kladis
A
A
Duncan
A M
AM
D000804:Angiotensin II / Q000097:blood / Q000378:metabolism*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000808:Angiotensinogen / Q000097:blood; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D008297:Male; D009392:Nephrectomy; D010455:Peptides / Q000097:blood / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D011863:Radioimmunoassay / Q000379:methods; D017257:Ramipril / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012083:Renin / Q000097:blood
D000806:Angiotensin-Converting Enzyme Inhibitors; D010455:Peptides; D000808:Angiotensinogen; D000804:Angiotensin II; D007703:Peptidyl-Dipeptidase A; D012083:Renin; D017257:Ramipril