Ramipril prevents basal arterial constriction and enhanced myogenic tone in the femoral artery in mildly uraemic normotensive rats

Some aspects of vascular reactivity are altered in mild experimental uraemi a, as shown by increased myogenic tone and a reduced lumen diameter in the femoral artery. This study was conducted to investigate the prevention of t hese uraemia-induced vascular abnormalities by the angiotensin-converting e nzyme inhibitor (ACE-I) Ramipril. Ten male Wistar rats were rendered uraemi c (U) by 5/6th nephrectomy, and 10 control (C) rats were concurrently sham- operated. After 4 weeks, both groups were given daily subcutaneous injectio ns of 3 mu g of Ramipril for a further 4 weeks. Tail-cuff systolic blood pr essure was then recorded and the rat was killed. Isolated femoral arteries were mounted on a pressure myograph and pressurized at 40 mmHg for baseline measurements of the lumen internal diameter. Myogenic tone was then assess ed over a range of intravascular pressures from 40 to 160 mmHg. Biochemical ly, serum urea and creatinine were significantly higher in the uraemic (U) group [urea: U, 23 +/- 3 mmol/l; C, 6 +/- 1 mmol/l (P < 0.001); creatinine: U, 147 +/- 17 mmol/l, C, 72 +/- 11 mmol/l (P < 0.01)]. Systolic blood pres sure was the same in both groups (U, 127 +/- 7 mmHg; C, 127 +/- 3 mmHg). Th e mean baseline internal diameter was the same in both groups (U, 756 +/- 2 2 mu m; C, 721 +/- 34 mu m, not significant), as was mean myogenic tone (U, 4.7 +/- 1%; C, 3.4 +/- 1%). In conclusion, there were no differences in ba seline lumen diameter or myogenic tone in uraemic compared with control fem oral arteries of rats treated with Ramipril, which suggests that Ramipril m ay prevent the development of elevated myogenic tone and decreased lumen di ameter previously observed in this model of uraemia. These results suggest that these specific vascular abnormalities uraemia may be mediated by renin or bradykinin, or by the direct action of angiotensin II on vascular smoot h muscle.