Inhibition of NO synthase prevents acute collateral artery dilation in the rat hindlimb.
The role of endothelium-derived nitric oxide (EDNO) in the initial opening and sustained dilation of collateral vessels in the peripheral circulation was investigated. Abrupt arterial occlusion was produced by clamping the rat superficial femoral artery (SFA). Arterial pressures were measured proximal (MAP) and distal (PD) to the occlusion site. In one group (INITIAL DILATION), the clamp was removed after PD reached a plateau, and then the nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME), was administered and the occlusion repeated in the same limb to evaluate the role of nitric oxide in the initial opening of collateral vessels. In another group (SUSTAINED DILATION), L-NAME was administered after acute compensation to SFA occlusion had occurred to determine if inhibition of nitric oxide synthase would reverse any acute compensation. Collateral dilation was evaluated by recovery in PD relative to MAP (PD-%MAP) and by the percent of total resistance in the collateral-dependent circuit due primarily to collaterals (%Rc). The acute compensation indicated by an increase in PD-%MAP (14 +/- 1.9% to 27 +/- 2.6%) and decrease in %Rc (86 +/- 1.9 to 73 +/- 2.6%) in the INITIAL DILATION group was prevented by L-NAME (P < 0.0005). L-NAME also reversed the compensation in the SUSTAINED DILATION group; PD-%MAP decreased from 28 +/- 2.3% to 11 +/- 1.9% and %Rc increased from 72 +/- 2.3% to 93 +/- 1.1% after administration of L-NAME. Although collateral flow was not measured, the results are consistent with the hypothesis that acute collateral dilation is mediated by increases in flow or shear stress which stimulate the release of EDNO.
Unthank
J L
JL
Department of Surgery, Indiana University Medical Center, Indianapolis, Indiana 46202, USA.
Nixon
J C
JC
Dalsing
M C
MC
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D003097:Collateral Circulation; D006614:Hindlimb / Q000098:blood supply; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects
D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester