Nitric oxide requirement for vasomotor nerve-induced vasodilatation and modulation of resting blood flow in muscle microcirculation.
Intravital microscopy of rabbit tenuissimus muscle was used for studies of endogenous nitric oxide as a microvascular regulator in vivo. Derivatives of arginine were administered in order to modulate the formation of nitric oxide from L-arginine. N omega-nitro-L-arginine methylester (L-NAME) (1-100 mg kg-1 i.v.) dose-dependently reduced microvascular diameters. A concomitant blood pressure increase and a decrease in heart rate was observed. The blood pressure increase induced by L-NAME (30 mg kg-1) was reversed by L-arginine (1 g kg-1) but not D-arginine. Vasodilation in response to topical acetylcholine (0.03-3 microM) was significantly inhibited by L-NAME (30 mg kg-1), whereas vasodilation by sodium nitroprusside (300 nM) was not affected. Vasomotor nerve-induced vasodilatation, induced by stimulation of the tenuissimus nerve after neuromuscular blockade by pancuronium in animals pretreated with guanethidine, was significantly attenuated by L-NAME, an effect also reversed by L-arginine. The vasodilatation in response to active contractions of the muscle induced by motor nerve stimulation as well as the vasodilator response elicited by graded perfusion pressure reductions were unaffected by L-NAME or NG-monomethyl-L-arginine (L-NMMA, 10(-4) M) administered topically. Our results indicate that endogenous nitric oxide formed from L-arginine is a modulator of microvascular tone in vivo. Furthermore, the results suggest that endogenous nitric oxide is required for vasomotor nerve-induced vasodilatation, whereas it does not appear to play a role in myogenic vasodilatation or functional hyperaemia in this tissue.
Persson
M G
MG
Department of Physiology, Karolinska Hospital, Karolinska Institutet, Stockholm, Sweden.
Wiklund
N P
NP
Gustafsson
L E
LE
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001160:Arterioles / Q000294:innervation / Q000502:physiology; D006614:Hindlimb; D008297:Male; D008833:Microcirculation / Q000502:physiology; D009132:Muscles / Q000098:blood supply* / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D011817:Rabbits; D012039:Regional Blood Flow / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014666:Vasomotor System / Q000187:drug effects / Q000502:physiology*; D019323:omega-N-Methylarginine
D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester