Central and peripheral haemodynamic effects of L-NAME infusion in healthy volunteers.
OBJECTIVE
To evaluate the effects of the intravenous administration of the nitric oxide synthesis inhibitor N(g)nitro-L-arginine methyl ester (L-NAME) in healthy volunteers.


METHODS
L-NAME (0.25, 0.5 and 0.75 mg/kg over 8 min) was infused in 13 healthy male volunteers. Finally, subjects were infused with either L- or D-arginine.


RESULTS
L-NAME resulted in dose-dependent falls in heart rate 60 bpm (55-64 bpm) to 49 bpm (46-52 bpm) (P<0.01) and increased mean arterial pressure 77.0 mmHg (73.2-80.8 mmHg) to 90.0 mmHg (87.1-92.8 mmHg) (P<0.01). The cardiac output was significantly reduced after each L-NAME infusion, and systemic vascular resistance increased linearly over the dosage range. Cardiac stroke volume was significantly reduced only following 0.75 mg/kg/min L-NAME: from 100 ml (91.3-108.7 ml) to 83 ml (74.7-91.4 ml); P<0.01. Forearm blood flow was unchanged at any dosage. L-arginine but not D-arginine infusion reversed the haemodynamic effects of L-NAME.


CONCLUSIONS
Contrasting with the profound dose-dependent effects of L-NAME had significant effects on central haemodynamics but no discernible effects on peripheral blood flow.
Morgan
D R
DR
Therapeutics and Pharmacology, The Whitla Division of Medicine, The Queen's University of Belfast, Whitla Medical Building, 97 Lisburn Road, BT9 7BL Belfast, Northern Ireland.
Silke
B
B
Dixon
L J
LJ
Allen
P B
PB
Hanratty
C G
CG
McVeigh
G E
GE
D004305:Dose-Response Relationship, Drug; D005542:Forearm / Q000098:blood supply / Q000000981:diagnostic imaging; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000494:pharmacology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D014463:Ultrasonography
D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester