Flow induces dilatation in the femoral artery of uraemic rats but constriction in control rats

Background. Pressure and flow are recognized as important modulators of vas cular tone. In mildly uraemic rats, myogenic tone is increased in the femor al 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, pressu rized at 80 mmHg, and constricted by 40-50% of the lumen internal diameter (i.d.) by L-phenylephrine (1-10 mu mol/l). Flow was initiated (0-207 mul/mi n) in six steps every 5 min and changes in i.d. recorded. N-nitro-L-arginin e methyl ester hydrochloride (L-NAME) (0.1 mmol/l) and 1H-[1,2,4] oxadiazol o-[4,3-a]quinoxalin-1-one (ODQ) (1 mu mol/l) were applied extraluminally an d the how protocol repeated. Results, The baseline pre-constricted at 80 mmHg i.d. was significantly sma ller in the U (U 255 +/- 21 mum Its C 365 +/- 36 mum, P < 0.03). At all ste ps, 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 significa nt basal reduction in i.d. was observed in the C only (C 365 +/- 36 mum vs C + L-NAME & ODQ 182 +/- 18 mum, P < 0.01; U 255 +/- 21 <mu>m vs U + L-NAME & ODQ 240 +/- 11 mum, P = n.s.). Furthermore, in the U there was no signif icant blunting to dilatation during flow (+9+4%). Conclusions, Flow elicited a constriction in controls, but a marked dilatat ion in uraemic roots which was not entirely nitric oxide dependent. These r esults suggest that other mediators such as prostacyclin or endothelium-dep endent hyperpolarizing factor, or changes in the vascular smooth muscle may contribute to flow-induced dilatation in mild experimental uraemia.