Nephrol Dial Transplant (2001) 16: 1156-1162
© 2001 European Renal Association-European Dialysis and Transplant Association
Flow induces dilatation in the femoral artery of uraemic rats but constriction in control rats
1 Anthony Raine Research Laboratories, St Bartholomew's Hospital, and 2 Fetal Health Research Group, Department of Obstetrics & Gynaecology, Guys, Kings & St Thomas’ Hospitals, London, UK
Background. Pressure and flow are recognized as important modulators of vascular tone. In mildly uraemic rats, myogenic tone is increased in the femoral artery in the absence of hypertension compared with healthy control rats, but the effect of flow in the same experimental model remains unknown.
Subjects and methods. Twelve male Wistar rats were rendered uraemic (U) by 5/6th nephrectomy or were concurrently sham operated as controls (C). After 8 weeks, isolated femoral arteries were mounted on a flow myograph, pressurized at 80 mmHg, and constricted by 40–50% of the lumen internal diameter (i.d.) by L-phenylephrine (1–10 µmol/l). Flow was initiated (0–207 µl/min) in six steps every 5 min and changes in i.d. recorded. N-nitro-L-arginine methyl ester hydrochloride (L-NAME) (0.1 mmol/l) and 1H-[1,2,4] oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ) (1 µmol/l) were applied extraluminally and the flow protocol repeated.
Results. The baseline pre-constricted at 80 mmHg i.d. was significantly smaller in the U (U 255±21 µm vs C 365±36 µm, P<0.03). At all steps, flow elicited a dilatation in the U and a constriction in the C (U+ 24±8% vs C-17±5%, P<0.01). When L-NAME and ODQ were applied, a significant basal reduction in i.d. was observed in the C only (C 365±36 µm vs C+ L-NAME & ODQ 182±18 µm, P<0.01; U 255± 21 µm vs U+L-NAME & ODQ 240±11 µm, P=n.s.). Furthermore, in the U there was no significant blunting to dilatation during flow (+9±4%).
Conclusions. Flow elicited a constriction in controls, but a marked dilatation in uraemic roots which was not entirely nitric oxide dependent. These results suggest that other mediators such as prostacyclin or endothelium-dependent hyperpolarizing factor, or changes in the vascular smooth muscle may contribute to flow-induced dilatation in mild experimental uraemia.
Keywords: femoral artery, flow; myography; nitric oxide; uraemia
Correspondence and offprint requests to: Dr T. Savage, Richard Bright Renal Unit, Southmead Hospital, Westbury-on-Trym, Bristol BS10 5NB, UK.