Endothelium-independent constriction of isolated, pressurized arterioles by Nomega-nitro-L-arginine methyl ester (L-NAME).
OBJECTIVE
Nitric oxide synthase (NOS) inhibitors cause vasoconstriction in pressurized arterioles with myogenic tone. This suggests either tonic production of NO modulates myogenic tone or a direct, NOS-independent effect of the NOS inhibitors. The nature of the contractile effect of the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME, 100 microM) on pressurised arterioles was investigated.


METHODS
Segments of rat cremaster muscle first-order arteriole were cannulated on glass micropipettes and maintained at an intraluminal pressure of 50, 70 or 120 mmHg.


RESULTS
L-NAME and the related compound L-NA (100 microM) constricted pressurized vessels with myogenic tone. Removal of the endothelium did not cause constriction or alter myogenic tone, however the constrictor effect of L-NAME persisted. The constrictor effect of L-NAME was abolished by L-arginine (1 mM). Other NO and cGMP pathway inhibitors, including the nNOS inhibitor 7-nitroindazole (100 muM), the NO scavenger carboxy-PTIO (100 microM), the guanylate cyclase inhibitor ODQ (10 microM) and the cGMP inhibitor Rp-8CPT-cGMPS (10 microM) did not cause constriction of the arterioles. L-NAME caused a small (3-4 mV) but not statistically significant depolarization of the arteriolar smooth muscle at both pressures. The constrictor effect was not prevented by the K(+)-channel antagonist tetraethyl ammonium (TEA, 1 mM) or the K(ATP) channel antagonist glibenclamide (1 microM).


CONCLUSIONS
These observations demonstrate that L-NAME causes an endothelium- and NOS-independent contraction of vascular smooth muscle in isolated skeletal muscle arterioles. It is suggested that the underlying mechanism relates to an arginine binding interaction.
Murphy
T V
TV
Department of Physiology and Pharmacology, School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia. tim.murphy@unsw.edu.au
Kotecha
N
N
Hill
M A
MA
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects; D000242:Cyclic AMP / Q000502:physiology; D004727:Endothelium / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D066298:In Vitro Techniques; D054086:KATP Channels; D008564:Membrane Potentials / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors*; D024661:Potassium Channels, Inwardly Rectifying / Q000037:antagonists & inhibitors; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects*
D004791:Enzyme Inhibitors; D054086:KATP Channels; D024661:Potassium Channels, Inwardly Rectifying; C092520:uK-ATP-1 potassium channel; D000242:Cyclic AMP; D052250:Nitric Oxide Synthase Type III; D006162:Guanylate Cyclase; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester