Nitric oxide: an important role in the maintenance of systemic and pulmonary vascular tone in man.
OBJECTIVE
The aim of this study was to examine whether nitric oxide (NO) has an important role in maintaining basal vascular tone in normal man by examining the effects of nitric oxide inhibition using N(G)-monomethyl-L-arginine (L-NMMA) on systemic and pulmonary haemodynamics.


METHODS
Ten normal male volunteers 26 +/- 1.6 years were studied on two separate occasions in a double-blind, placebo controlled crossover study. They were randomised to receive either a continuous infusion of L-NMMA (4 mg kg(-1) h(-1)) with a front loaded bolus (4 mg kg(-1)) or volume matched placebo. Pulsed wave Doppler echocardiography was used to measure cardiac output (CO), mean pulmonary artery pressure (MPAP) and hence systemic vascular resistance (SVR) and total pulmonary vascular resistance (TPR). Measurements were made prior to infusion (t0) and after 4, 8, and 12 min (t1, t2 and t3).


RESULTS
Infusion of L-NMMA significantly increased mean arterial blood pressure (MAP), SVR and TPR and significantly reduced heart rate (HR), stroke volume (SV) and CO compared to placebo. These effects were observed at t1 and persisted during the entire infusion period.


CONCLUSIONS
These results are consistent with a role for basal nitric oxide generation in the maintenance of basal systemic and pulmonary vascular tone in normal man.
Department of Clinical Pharmacology, Ninewells Hospital and Medical School, Dundee, Scotland, UK.
D G
DG
Kiely
A F
AF
Lee
A D
AD
Struthers
B J
BJ
Lipworth
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D015150:Echocardiography, Doppler; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000502:physiology; D010919:Placebos; D011651:Pulmonary Artery / Q000187:drug effects* / Q000502:physiology; D011652:Pulmonary Circulation / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D019323:omega-N-Methylarginine / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D010919:Placebos; D019323:omega-N-Methylarginine; D009569:Nitric Oxide