Differential inhibition by NG-monomethyl-L-arginine of vasodilator effects of acetylcholine and methacholine in human forearm vasculature.
1. We compared the effects of NG-monomethyl-L-arginine (L-NMMA), an NO synthase inhibitor, on vasodilatation produced by acetylcholine and methacholine in human forearm vasculature. 2. Acetylcholine (83 nmol min-1) infused into the brachial artery of 8 healthy volunteers caused a submaximal increase in forearm blood flow, measured by venous occlusion plethysmography, from 3.3 +/- 0.5 (mean +/- s.e. mean) to 13.3 +/- 1.7 ml min-1 100 ml-1. 3. Co-infusion of L-NMMA (4 mumol min-1) with acetylcholine (83 nmol min-1) over 6 min resulted in a 58% +/- 12% fall in the response to acetylcholine whereas during co-infusion of saline over the same time period in the same subjects (n = 8) on a different day the response to acetylcholine fell by only 9% +/- 17% (P < 0.01). 4. Methacholine (1.5 and 15 nmol min-1) increased forearm blood flow from 2.5 +/- 0.4 to 5.9 +/- 0.9 and from 3.2 +/- 0.4 to 17.0 +/- 1.9 ml min-1 100 ml-1 respectively. 5. Co-infusion of L-NMMA (4 mumol min-1) had no significant effect on the response to methacholine (1.5 or 15 nmol min-1) when compared with saline control (n = 8). Co-infusion of a higher dose of L-NMMA (8 mumol min-1) with methacholine (1.5 nmol min-1) did not significantly inhibit the vasodilator response (n = 7). 6. These results suggest that, in human forearm vasculature, methacholine acts predominantly through mechanisms other than the L-arginine/nitric oxide pathway.
Chowienczyk
P J
PJ
Department of Clinical Pharmacology, UMDS, Guy's Hospital, London.
Cockcroft
J R
JR
Ritter
J M
JM
D000109:Acetylcholine / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005542:Forearm / Q000098:blood supply*; D006801:Humans; D007231:Infant, Newborn; D007262:Infusions, Intravenous; D008688:Methacholine Compounds / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008875:Middle Aged; D010991:Plethysmography; D012039:Regional Blood Flow / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D019323:omega-N-Methylarginine
D008688:Methacholine Compounds; D014665:Vasodilator Agents; D019323:omega-N-Methylarginine; D001120:Arginine; D000109:Acetylcholine