Effect of NG-monomethyl-L-arginine on kinin-induced vasodilation in the human forearm.
1. We compared effects of NG-monomethyl-L-arginine (L-NMMA), an NO synthase inhibitor, on vasodilator responses to intra-arterial infusion of bradykinin and substance P in the human forearm. 2. Bradykinin (100 pmol min-1) increased forearm blood flow when infused into the brachial artery of eight healthy male volunteers, from 2.8 +/- 0.2 (mean +/- s.e. mean) to 9.3 +/- 1.0 ml min-1 per 100 ml forearm volume. 3. Co-infusion of L-NMMA (2 mumol min-1 and 4 mumol min-1) with bradykinin (100 pmol min-1) for 6 min produced respectively a 9 +/- 14% and 42 +/- 14% inhibition (compared with L-NMMA vehicle) in the response to bradykinin. 4. Substance P (1 pmol min-1) when infused into the brachial artery of a further eight male subjects increased forearm blood flow from 3.4 +/- 0.2 to 6.3 +/- 0.7 ml min-1 100 ml-1. 5. Co-infusion of L-NMMA (2 mumol min-1 and 4 mumol min-1) with substance P (1 pmol min-1) for 6 min produced respectively a 27 +/- 8% and 70 +/- 13% inhibition (compared with L-NMMA vehicle) in the response to substance P. 6. These results demonstrate that vasodilator responses to both bradykinin and substance P are mediated in part via the L-arginine/NO pathway. Bradykinin and substance P may be useful agonists with which to study endothelial function in this vascular bed.
Cockcroft
J R
JR
Department of Clinical Pharmacology, United Medical School, Guy's Hospital, London.
Chowienczyk
P J
PJ
Brett
S E
SE
Ritter
J M
JM
D000328:Adult; D000704:Analysis of Variance; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D001916:Brachial Artery / Q000187:drug effects / Q000378:metabolism; D001920:Bradykinin / Q000008:administration & dosage / Q000494:pharmacology*; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000187:drug effects; D005542:Forearm; D006801:Humans; D007261:Infusions, Intra-Arterial; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D010991:Plethysmography; D012039:Regional Blood Flow / Q000187:drug effects; D013373:Substance P / Q000008:administration & dosage / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*; D019323:omega-N-Methylarginine
D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D013373:Substance P; D001120:Arginine; D001920:Bradykinin