Effects of norepinephrine on endothelium-dependent vasodilation of forearm resistance vessels.
BACKGROUND
Endothelium-dependent dilatation of forearm resistance vessels is attenuated in patients with heart failure. Activation of the sympathetic nervous system could cause this abnormality by way of vasoconstriction and chemical inactivation of nitric oxide.


RESULTS
The effects of concurrent intra-arterial norepinephrine infusions (25, 50 and 100 ng/min) on forearm blood flow responses to equipotent doses of an endothelium-dependent vasodilator, methacholine (0.3 and 1.5 micrograms/min), and an endothelium-independent vasodilator, nitroprusside (1 and 5 micrograms/min), were studied in 12 normal subjects. Norepinephrine infusions increased the mean plasma norepinephrine from 255 pg/ml at baseline to 460, 629, and 1089 pg/ml, respectively. Basal forearm blood flow was reduced from 2.9 to 1.6 ml/min/100 ml of forearm volume at the highest dose (p < 0.01). The average response to the lowest dose of methacholine (4.5 ml/min/100 ml) was not significantly reduced by concurrent infusion of norepinephrine (4.4, 4.2, and 4.3 ml/min/100 ml, respectively), whereas the response to the higher dose of methacholine (8.9 ml/min/100 ml) tended to be lower (7.2, 6.7, and 7.4 ml/min/100 ml, respectively) but did not attain statistical significance. Methacholine induced vasodilation was not more sensitive to norepinephrine than nitroprusside responses. Lower body negative pressure (-20 mm Hg) also significantly reduced baseline forearm flow and increased plasma norepinephrine but did not effect either methacholine or nitroprusside induced vasodilation.


CONCLUSIONS
Sympathetic stimulation induced by infusion of norepinephrine or lower body negative pressure is not a potent antagonist to endothelium-dependent vasodilation of the forearm vasculature. These data suggest that sympathetic activation does not completely explain the abnormal endothelium-dependent vasodilation seen in patients with heart failure.
Rector
T S
TS
Cardiovascular Division, University of Minnesota Medical School, Minneapolis 55455.
Bank
A J
AJ
De Bruyn
V H
VH
Garr
M D
MD
Kraemer
M D
MD
Kubo
S H
SH
D000328:Adult; D000704:Analysis of Variance; D004730:Endothelium, Vascular / Q000187:drug effects*; D005542:Forearm / Q000098:blood supply*; D006801:Humans; D008150:Lower Body Negative Pressure; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology*; D012016:Reference Values; D014655:Vascular Resistance / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
D016210:Methacholine Chloride; D009599:Nitroprusside; D009638:Norepinephrine