The role of nitric oxide in mediating adenosine-induced increases in uterine blood flow in the oophorectomized nonpregnant sheep.
OBJECTIVE
Adenosine administration to the uterine vasculature of the nonpregnant oophorectomized sheep results in dose-related increases in uterine blood flow. This study was designed to determine whether these adenosine-induced increases in uterine blood flow are mediated in part by nitric oxide release.


METHODS
Five nonpregnant oophorectomized ewes had catheters placed in the femoral artery and vein and in the lateral branches of the right and left main uterine arteries. Adenosine dissolved in isotonic sodium chloride solution was infused into the uterine artery at sequentially increasing doses (1, 3, 10, 30, 100, and 300 microg/min), and a dose-response curve was constructed. After determination of control responses to adenosine a 10-mg/kg dose of the nitric oxide synthase inhibitor N omega-nitro-L -arginine methyl ester was administered into the femoral vein; the dose-response curves to adenosine were then determined again. Responses after N omega-nitro-L -arginine methyl ester administration were compared with those obtained before nitric oxide blockade.


RESULTS
Adenosine increased uterine blood flow in a dose-related fashion, from a baseline of 11 +/- 2 mL/min to 140 +/- 19 mL/min. No further increase was seen with adenosine doses >300 microg/min. There were no significant alterations in systemic arterial pressure or heart rate in response to uterine infusion of adenosine. N omega-nitro-L -arginine methyl ester administration increased baseline blood pressure 24% +/- 4% and decreased heart rate 13% +/- 4%. Responses to adenosine after N omega-nitro-L -arginine methyl ester administration were significantly reduced, from a maximum at the highest dose of 140 +/- 19 mL/min to 95 +/- 13 mL/min (P <.001).


CONCLUSIONS
A significant portion of adenosine-induced vasodilation in the uterine vasculature appears to be mediated by the release of nitric oxide.
Carpenter
L B
LB
Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Cincinnati College of Medicine, OH 45267- 0526, USA.
Baker
R S
RS
Greenberg
S
S
Clark
K E
KE
D000241:Adenosine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010052:Ovariectomy; D012756:Sheep; D014599:Uterus / Q000098:blood supply*
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000241:Adenosine; D019331:NG-Nitroarginine Methyl Ester