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 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 micromol/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.
Benchetrit
S
S
Department of Nephrology and Hypertension, Meir Hospital and Sapir Medical Center, Sackler School of Medicine, Tel-Aviv University, Israel.
Mandelbaum
A
A
Bernheim
J
J
Podjarny
E
E
Green
J
J
Katz
B
B
Rathaus
M
M
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D006493:Heparin / Q000494:pharmacology*; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009392:Nephrectomy; D009566:Nitrates / Q000652:urine; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013599:Systole
D000959:Antihypertensive Agents; D009566:Nitrates; D006493:Heparin; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine