Effects of converting enzyme inhibitors on angiotensin and bradykinin peptides.

Abstract

We examined the dose-related effects of angiotensin-converting enzyme inhibitors on circulating and tissue levels of angiotensin and bradykinin peptides by administering perindopril or lisinopril to rats in drinking water for 7 days. A reduction in the ratio of plasma angiotensin II (Ang II) to Ang I was seen for 0.006 mg/kg per day perindopril, with an increase in plasma renin and Ang I at 0.017 mg/kg per day. Plasma Ang II levels did not decrease until 1.4 mg/kg per day perindopril, at which dose plasma Ang I levels reached a plateau of an approximate 25-fold increase. The effects of perindopril on Ang II and Ang I levels in heart, lung, aorta, and brown adipose tissue were parallel to those observed for plasma. By contrast, renal Ang I levels did not increase, and renal Ang II levels decreased by 40% at 0.017 mg/kg per day, the same threshold seen for the increase in plasma renin. Perindopril increased circulating bradykinin-(l-9) levels approximately eightfold, with a threshold dose of 0.052 mg/kg per day, and increased bradykinin-(l-9) levels in kidney, heart,

Angiotensin-converting enzyme inhibition reverses diet-induced obesity, insulin resistance and inflammation in C57BL/6J mice

“…22,31 This could be because of increased bradykinin levels 44 or increased ANG-II synthesis in the brain. 45 As the fluid intake by the CAP-treated mice is elevated compared with that of the CON group, the reduction in food intake by the CAPtreated mice is not due to a general suppression of behaviour by CAP.…”

ACE-I vs angiotensin II receptor antagonists: prevention of renal injury in chronic rat models

“…Although both ACE-I and AT 1 RA are effective in inhibiting the RAA system, they differ significantly in their effects on the components of the system. While ACE inhibition results in reduced levels of Ang II and elevated levels of renin and bradykinin, 19 AT 1 RA produces elevations in both renin and Ang II, and has no effect on bradykinin. 12 These differences may represent significant advantages of AT 1 RA over ACE-I in two respects.…”

Blood pressure and renal hemodynamic effects of angiotensin fragments

“…139,144 Hypertensive animals treated with ACE inhibitors had a 25-to 50-fold increase of circulating levels of Ang-(1-7), suggesting that Ang-(1-7) might contribute to the antihypertensive effects produced by ACE inhibitors. [145][146][147] The role of Ang-(1-7) in the regulation of kidney function is not well understood and conflicting data were reported. Some groups failed to detect effects of Ang-(1-7) on RBF in rats, 145,148 but others observed a renal vasodilator response, and reported afferent arteriolar dilatation mediated by NO.…”