Renal norepinephrine spillover during infusion of nonesterified fatty acids.
BACKGROUND
Sympathetic activity and renal norepinephrine spillover are increased in obese individuals. We have reported that infusion of nonesterified fatty acids increases blood pressure in animals through stimulation of the sympathetic nervous system.


METHODS
In this study, we assessed the effect of increasing circulating nonesterified fatty acids on systemic and renal norepinephrine kinetics in healthy adults by infusing fat emulsion and heparin for 4 h. (3)H-norepinephrine was infused for 60 min before and again during the last hour of the fatty acid infusion to assess norepinephrine kinetics. Renal venous blood samples were obtained to calculate renal norepinephrine spillover.


RESULTS
Nonesterified fatty acid levels increased threefold during the first hour and remained elevated throughout the study. Arterial and renal venous plasma norepinephrine levels fell by 15% and 20%, respectively, during the infusion (P < .05 for both). Kinetic analysis indicated that systemic release of norepinephrine into an extravascular compartment decreased from 11.6 +/- 1.1 to 10.0 +/- 1.3 nmol/min/m(2) (P = .067) and renal venous norepinephrine spillover decreased from 454 +/- 54 pmol/min (P = .055).


CONCLUSIONS
These results indicate that nonesterified fatty acids do not have a direct stimulating effect on whole-body or renal sympathetic activity. It is possible that increased plasma levels of fatty acids serve as a signal to decrease sympathetic tone during the fasting state.
Grekin
Roger J
RJ
Veterans Affairs Ann Arbor Healthcare System, 2215 Fuller Road, Ann Arbor, MI 48105, USA. rgrekin@umich.edu
Ngarmukos
Chardpra-Orn
CO
Williams
David M
DM
Supiano
Mark A
MA
D000328:Adult; D000925:Anticoagulants / Q000008:administration & dosage; D005217:Fat Emulsions, Intravenous / Q000008:administration & dosage; D005230:Fatty Acids, Nonesterified / Q000008:administration & dosage* / Q000097:blood; D005260:Female; D006493:Heparin / Q000008:administration & dosage; D006801:Humans; D006977:Hypertension, Renal / Q000209:etiology* / Q000378:metabolism; D007668:Kidney / Q000294:innervation* / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000493:pharmacokinetics*; D009765:Obesity / Q000150:complications* / Q000378:metabolism; D012083:Renin / Q000097:blood; D013564:Sympathetic Nervous System / Q000502:physiology; D014316:Tritium
D000925:Anticoagulants; D005217:Fat Emulsions, Intravenous; D005230:Fatty Acids, Nonesterified; D014316:Tritium; D006493:Heparin; D012083:Renin; D009638:Norepinephrine