Nephrology Dialysis Transplantation, Vol 14, Issue 1 64-69, Copyright © 1999 by Oxford University Press
S Benchetrit, A Mandelbaum, J Bernheim, E Podjarny, J Green, B Katz and M Rathaus
Background: This study was designed to assess whether
the antihypertensive effect of heparin in rats after renal mass reduction
(RMR) is related to changes 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 protocols. In the first protocol, RMR rats received heparin
(250 units/day s.c.) and 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 (70 mg/l
added to the drinking water) prevents the blood-pressure-lowering 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, SBP was 114±3 mmHg at 2 weeks and 111±4 mmHg
at 4 weeks (P<0.05 for both). Treatment with L-NAME increased SBP
both in untreated and heparin-treated RMR group. Two weeks after
nephrectomy daily urinary nitrate increased significantly more in RMR rats
treated with heparin than in untreated RMR rats (22±2
vs 14.2±2.3 &mgr;mol/day,
P<0.05). In vitro studies performed at 2 weeks
showed that vessels of untreated RMR rats had a blunted vasodilator
response to acetyl-choline that was restored to levels similar to that of
controls in the heparin-treated group. Conclusions:
These results suggest that, in rats after renal ablation, heparin may exert
its antihypertensive effect, at least in part, by affecting the altered
behaviour of resistance vessels during the development phase of
hypertension. Increased NO production may contribute to this effect.
Key words: blood pressure; heparin; mesenteric
arteries; nephrectomy; nitric oxide; partial nephrectomy; rat; vascular
reactivity
ORIGINAL ARTICLES
Altered vascular reactivity following partial nephrectomy in the rat: a possible mechanism of the blood-pressure-lowering effect of heparin
Department of Nephrology and Hypertension, Meir Hospital and Sapir Medical Center, Sackler School of Medicine, Tel-Aviv University, Israel; Corresponding author at: Meir Hospital, 44281 Kfar Saba, Israel
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