title: NG-monomethyl-L-ARG reduces the forearm vasodilator response to acetylcholine but not to methacholine in humans.
abstract: We compared the contribution of nitric oxide (NO) in methacholine (MCh)- and acetylcholine (ACh)-induced vasodilation using the NO-synthase inhibitor NG-monomethyl-L-arginine acetate (L-NMMA-acetate) in two groups (A and B) of 6 healthy male volunteers. The left brachial artery was cannulated for drug infusion and recording of mean arterial pressure (MAP). Forearm blood flow (FBF) was measured on both sides by venous occlusion mercury-in-silastic strain-gauge plethysmography. All measurements were performed with occluded hand circulation. Forearm vasodilator response to three increasing dosages of MCh (0.03, 0.3, and 1 micrograms/100 ml forearm/min; group A) or ACh (0.5, 2, and 8 micrograms/100 ml forearm/min; group B) was studied first. Forty-five minutes later, these infusions were repeated (after and during local administration of L-NMMA). L-NMMA-acetate infusion alone increased basal forearm vascular resistance (FVR, mean +/- SE) by 86.2 +/- 14.5 and 99.5 +/- 27.4% in groups A and B, respectively (p < 0.05) without significant FVR changes in the control arm. MCh-induced vasodilation was not attenuated by concomitant L-NMMA-acetate infusion. In contrast, L-NMMA-acetate significantly reduced the averaged percentage decrease in FVR during infusion of ACh from 55.7 +/- 9.1 to 35.4 +/- 11.8% (p < 0.05). L-NMMA-acetate increased basal vascular tone and reduced the vasodilator response to ACh. MCh induced vasodilation to a degree similar to that obtained with ACh. Nevertheless, MCh-induced vasodilation could not be attenuated by L-NMMA, suggesting that NO contributes differentially to methacholine- and ACh-induced vasodilation in humans.
authors.affiliation: Department of Medicine, University Hospital Nijmegen, The Netherlands.
authors.forename: G A
authors.initials: GA
authors.lastname: Rongen
authors.forename: P
authors.initials: P
authors.lastname: Smits
authors.forename: T
authors.initials: T
authors.lastname: Thien
mesh_terms: D000109:Acetylcholine / Q000008:administration & dosage / Q000494:pharmacology*; D000293:Adolescent; D000328:Adult; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D005542:Forearm / Q000098:blood supply; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D016210:Methacholine Chloride / Q000008:administration & dosage / Q000494:pharmacology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D010991:Plethysmography; D012039:Regional Blood Flow / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*; D019323:omega-N-Methylarginine
chemical_list: D016210:Methacholine Chloride; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D000109:Acetylcholine