Evidence of a nonendothelial source of nitric oxide in the isolated perfused hindlimb vasculature of the pregnant rat.
OBJECTIVE
This study was undertaken to further elucidate the roles of the vascular endothelium and nitric oxide (NO) in the regulation of vascular tone and constrictor responsiveness in pregnancy.


METHODS
The perfusion pressure-flow relationship was measured in isolated, perfused, norepinephrine-constricted (1) endothelium-intact, (2) endothelium-denuded, and (3) N omega-nitro-L-arginine methyl ester (L-NAME)-treated hindlimbs from nonpregnant and term-pregnant rates.


RESULTS
Baseline perfusion pressure at a flow rate of 2 mL/min was similar (approximately 20 min Hg) in all hindlimbs. Norepinephrine (0.5 muM) increased perfusion pressure in both nonpregnant (+21.6 +/- 2.4 mm Hg) and pregnant (+13.6 +/- 0.9 mm Hg) endothelium-intact rat hindlimbs. In nonpregnant rat hindlimbs, endothelium removal and L-NAME increased norepinephrine vasoconstriction similarly (+44.3 +/- 4.0 mm Hg and +46.4 +/- 8.6 mm Hg, respectively). In pregnant-rat hindlimbs, L-NAME increased norepinephrine vasoconstriction by 43.5 +/- 10.8 mm Hg, similar to that in nonpregnant-rat hindlimbs, but endothelium removal only increased norepinephrine vasoconstriction by 28.0 +/- 2.2 mm Hg. Perfusion pressure increased linearly as the flow rate was increased from 2 to 4 mL/min, and the slope of the regression line of the endothelium-intact pregnant-rat hindlimbs (7.0 +/- 0.6) was slightly, but not significantly, lower than that of the nonpregnant-rat hindlimbs (9.6 +/- 0.9). Endothelium removal increased the slopes of the regression lines, but that of pregnant-rat hindlimbs (12.8 +/- 1.6) was significantly lower (p < or = 0.05) than that of the nonpregnant-rat hindlimbs (23.8 +/- 1.8). L-NAME caused a similar increase in the pressure-flow slopes of nonpregnant-rat (36.5 +/- 3.4) and pregnant-rat (32.1 +/- 5.3) hindlimbs.


CONCLUSIONS
These results suggest that nonendothelial nitric oxide production may be increased in the hindlimb resistance vasculature of the pregnant rat, which may play a role in the normal pregnancy blunting of constrictor responsiveness and reduction of vascular resistance.
Lubarsky
S L
SL
Department of Obstetrics and Gynecology, University of Tennessee, Memphis 38103, USA.
Sibai
B M
BM
Ahokas
R A
RA
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006614:Hindlimb / Q000098:blood supply; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D009638:Norepinephrine / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D011921:Rats, Inbred WKY; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009569:Nitric Oxide; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine