Effect of local intra-arterial NG-monomethyl-L-arginine in patients with hypertension: the nitric oxide dilator mechanism appears abnormal.
OBJECTIVE
There is indirect evidence that the nitric oxide system may be impaired in hypertensive patients. The objective of this study was to examine basal nitric oxide-mediated dilation in hypertensive patients.


METHODS
The forearm blood flow (FBF) response to noradrenaline and NG-monomethyl-L-arginine (L-NMMA), a stereospecific inhibitor of nitric oxide synthesis, was compared in seven untreated hypertensive patients and 17 normotensive controls.


METHODS
Drugs were infused locally into the brachial artery and FBF measured using venous occlusion plethysmography.


RESULTS
In normotensives noradrenaline (60, 120 and 240 pmol/min) and L-NMMA (1,2 and 4 mumol/min) produced similar reductions in resting FBF. In the hypertensives L-NMMA was significantly less effective than noradrenaline, such that the threshold dose for L-NMMA vasoconstriction was increased and the overall response to L-NMMA reduced. Furthermore, when noradrenaline was used as an internal control there was a significant negative relationship between the response to L-NMMA and blood pressure. When the responses to L-NMMA and noradrenaline were compared between groups, the response to L-NMMA was significantly less in hypertensives compared with normotensives, whereas there was no statistical difference in the response to noradrenaline between the two groups.


CONCLUSIONS
The results suggest an abnormality of basal nitric oxide-mediated dilation in the forearm arteriolar bed of patients with untreated essential hypertension.
Calver
A
A
Department of Pharmacology and Clinical Pharmacology, St George's Hospital Medical School, London, UK.
Collier
J
J
Moncada
S
S
Vallance
P
P
D000328:Adult; D000367:Age Factors; D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology*; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*; D019323:omega-N-Methylarginine
D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D009638:Norepinephrine