Effects of ACE inhibition and bradykinin antagonism on cardiovascular changes in uremic rats (original) (raw)

2000, Kidney International

Conclusion. These findings illustrate that bradykinin plays Effects of ACE inhibition and bradykinin antagonism on caran important role for the beneficial effect of Ramipril in prediovascular changes in uremic rats. venting (and potentially reversing) abnormal cardiovascular Background. Cardiovascular death continues to be a major structure in uremic hypertensive rats. problem in renal failure. Structural abnormalities of the heart and the vasculature contribute to the increased cardiovascular risk. They are ameliorated by angiotensin-converting enzyme (ACE) inhibitors, but because of the nonspecifity of ACE Increased cardiovascular mortality continues to be an inhibition, it is uncertain whether the beneficial effect is mediunresolved problem of chronic renal failure. The genesis ated by interfering with angiotensin II (Ang II) or by modulating other effector systems, for example, bradykinin. is multifactorial, but abnormalities in cardiovascular Methods. To assess a potential role of bradykinin, subtotally structure play a major role [1]. The administration of nephrectomized Sprague-Dawley rats (SNX) received either angiotensin-converting enzyme inhibitors (ACEi) sigthe ACE inhibitor Ramipril (Rami, 0.2 mg/kg body weight nificantly improves the structural abnormalities in experp.o.), the specific B2 bradykinin receptor antagonist Hoe140 (0.2 mg/kg body weight, s.c.), or a combination of both, and imental and clinical studies [2, 3]. In particular, in experiwere compared to sham-operated controls. To separately assess mental renal failure left ventricular hypertrophy (LVH), the effect of Ramipril on development and reversal of strucinterstitial fibrosis and arteriolar wall thickening were tural abnormalities, animals were either treated from the third prevented by ACEi, whereas reduced myocardial capilday after SNX or from the fourth week after SNX onward lary supply was not affected [4]. Furthermore, in a con-(0.01 mg/kg body weight, p.o.). Results. Heart and aorta were evaluated by morphometric