Altered vascular reactivity following partial nephrectomy in the rat: a possible mechanism of the blood-pressure-lowering effect of heparin

Background. This study was designed to assess whether the antihypertensive effect of heparin in rats after renal mass reduction (RMR) is related to ch anges in nitric oxide activity, and to study in vitro the altered behaviour of resistance-sized arteries induced by chronic administration of heparin. Methods. Male Wistar rats were assigned to one of two experimental protocol s. In the first protocol, RMR rats received heparin (250 units/day s.c.) an d tail systolic blood pressure (SBP) was measured weekly for 4 weeks. In a subgroup, urinary nitrate excretion (UNO3) and in vitro vascular reactivity of isolated perfused mesenteric arterial beds were measured 2 weeks after RMR. The second protocol assessed whether inhibition of NO synthesis with L -NAME (70mg/l added to the drinking water) prevents the blood-pressure-lowe ring effect of heparin. Results. In untreated RMR rats SBP increased from 111 +/- 3 mmHg to 127 +/- 5 mmHg at 2 weeks and 139 +/- 5 mmHg at 4 weeks. In contrast, in RMR rats treated with heparin, SEP was 114 +/- 3 mmHg at 2 weeks and 115 +/- 4 mmHg at 4 weeks (P<0.05 for both). Treatment with L-NAME increased SEP both in u ntreated and heparin-treated RMR groups. Two weeks after nephrectomy daily urinary nitrate increased significantly more in RMR rats treated with hepar in than in untreated RMR rats (22 +/- 2 vs 14.2 +/- 2.3 mu mol/day, P<0.05) . In vitro studies performed at 3 weeks showed that vessels of untreated RM R rats had a blunted vasodilator response to acetylcholine that was restore d to levels similar to that of controls in the heparin-treated group. Conclusions. These results suggest that, in rats after renal ablation, hepa rin may exert its antihypertensive effect, at least in part, by affecting t he altered behaviour of resistance vessels during the development phase of hypertension. Increased NO production may contribute to this effect.