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

Sydney Benchetrit, Alexander Mandelbaum, Jacques Bernheim, Eduardo Podjarny, Janice Green, Bernardo Katz, Mauro Rathaus

Research output: Contribution to journalArticlepeer-review

Abstract

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 115 ± 4 mmHg at 4 weeks (P < 0.05 for both). Treatment with L-NAME increased SBP both in untreated and heparin-treated RMR groups. 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 μmol/day, P < 0.05). In vitro studies performed at 2 weeks showed that vessels of untreated RMR rats had a blunted vasodilator response to acetylcholine 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.

Original languageEnglish
Pages (from-to)64-69
Number of pages6
JournalNephrology Dialysis Transplantation
Volume14
Issue number1
DOIs
StatePublished - 1999

Keywords

  • Blood pressure
  • Heparin
  • Mesenteric arteries
  • Nephrectomy
  • Nitric oxide
  • Partial nephrectomy
  • Rat
  • Vascular reactivity

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