Early endothelial dysfunction following renal mass reduction in rats.
BACKGROUND
Endothelial dysfunction has been previously described in severely hypertensive rats with renal mass reduction (RMR) receiving large dietary Na loads. Because hypertension and Na loading reduce endothelium-dependent vasodilation, the effect of renal failure per se is unclear.


METHODS
Responses to acetylcholine in noradrenaline-contracted isolated perfused mesenteric arteries were studied. Vessels were obtained from RMR rats kept on a normal diet, 3 and 10 days after surgery, and the results were compared with those from sham-operated rats (SN). The role of three putative mediators of endothelium-dependent vasodilation was assessed using: L-NAME (10(-4) mol L(-1)); indomethacin (INDO, 10(-5) mol L(-1)); and a mixture of charybdotoxin and apamin (C/A, both 10(-7) mol L(-1)), inhibitors of Ca-activated K-channels to mediate the effects of endothelium-derived hyperpolarizing factor (EDHF).


RESULTS
Response to acetylcholine but not that to nitroprusside (endothelium-independent) was decreased in RMR. L-NAME reduced further acetylcholine relaxations in SN but not in RMR. By contrary, INDO decreased acetylcholine vasodilation in RMR but had no effect in SN. C/A had similar effects in the SN and RMR rats. The levels of 6-keto prostaglandin F1alpha were elevated in the urine of the RMR rats and were perfusate from the RMR vessels.


CONCLUSIONS
Endothelial dysfunction occurs early after RMR, even when systolic blood pressure is only minimally elevated and Na intake is normal. This alteration may be because of decreased availability of nitric oxide, partially compensated by increased prostacyclin production.
Benchetrit
S
S
Department of Nephrology and Hypertension, Meir Hospital-Sapir Medical Center, 44281 Kfar Saba, Israel.
Green
J
J
Katz
D
D
Bernheim
J
J
Rathaus
M
M
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D046508:Culture Techniques; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006977:Hypertension, Renal / Q000503:physiopathology*; D008297:Male; D008638:Mesenteric Arteries / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009392:Nephrectomy; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D014665:Vasodilator Agents; D015121:6-Ketoprostaglandin F1 alpha; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine