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 uraemia, as shown by increased myogenic tone and a reduced lumen diameter in the femoral artery. This study was conducted to investigate the prevention of these uraemia-induced vascular abnormalities by the angiotensin-converting enzyme inhibitor (ACE-I) Ramipril. Ten male Wistar rats were rendered uraemic (U) by 5/6th nephrectomy, and 10 control (C) rats were concurrently sham-operated. After 4 weeks, both groups were given daily subcutaneous injections of 3 microg of Ramipril for a further 4 weeks. Tail-cuff systolic blood pressure 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 assessed over a range of intravascular pressures from 40 to 160 mmHg. Biochemically, 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 pressure was the same in both groups (U, 127+/-7 mmHg; C, 127+/-3 mmHg). The mean baseline internal diameter was the same in both groups (U, 756+/-22 microm; C, 721+/-34 microm, not significant), as was mean myogenic tone (U, 4.7+/-1%; C, 3.4+/-1%). In conclusion, there were no differences in baseline lumen diameter or myogenic tone in uraemic compared with control femoral arteries of rats treated with Ramipril, which suggests that Ramipril may prevent the development of elevated myogenic tone and decreased lumen diameter previously observed in this model of uraemia. These results suggest that these specific vascular abnormalities in uraemia may be mediated by renin or bradykinin, or by the direct action of angiotensin II on vascular smooth muscle.
Savage
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Anthony Raine Research Laboratories, St. Bartholomews Hospital, Dominion House, 59 Bartholomew Close, West Smithfield, London EC1A 7BE, U.K.
McMahon
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AC
Mullen
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Tribe
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RM
Yaqoob
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MM
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D005263:Femoral Artery / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D009129:Muscle Tonus / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology; D009213:Myography; D017257:Ramipril / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014511:Uremia / Q000503:physiopathology*; D014661:Vasoconstriction / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D017257:Ramipril