Leptin is an endothelial-independent vasodilator in humans with coronary artery disease: Evidence for tissue specificity of leptin resistance.
OBJECTIVE
We sought to define the mechanisms and correlates of leptin's vascular actions in humans with coronary artery disease.


RESULTS
In 131 patients (age 65.7+/-0.7 years mean+/-SEM), ex vivo vascular reactivity to leptin (10(-13)-10(-7) M) was assessed in saphenous vein (SV) rings. Leptin led to SV relaxation (maximal relaxation 24.5+/-1.6%). In separate experiments, relaxation to leptin was unaffected by L-NMMA (17.4+/-3.4 vs.17.8+/-3.3%, P = 0.9) or endothelial denudation (17.4+/-4.4 vs. 22.5+/-3.0%, P = 0.4). We explored the possibility that leptin's vascular effects are mediated via smooth muscle hyperpolarization. In the presence of KCl (30 mmol/L) to inhibit hyperpolarization, the vasodilator effect of leptin was completely blocked (0.08+/-4.1%, P < 0.001 vs. control). Similar results were demonstrated in internal mammary artery rings. The only independent correlate of leptin-mediated vasodilatation was plasma TNF-alpha (r = 0.25, P < 0.05). Neither body mass index nor waist circumference correlated with leptin-mediated vasorelaxation. This lack of a correlation with markers of total body fat/fat distribution suggests that leptin resistance may not extend to the vasculature.


CONCLUSIONS
Leptin is a vasoactive peptide in human SV and internal mammary artery. Its action is not nitric oxide or endothelial-dependent. Markers of body fat did not correlate with leptin-mediated vasodilatation, raising the intriguing possibility of selective resistance to leptin's actions.
Cardiovascular Division, King's College School of Medicine at Guy's, King's College, and St Thomas' Hospitals, King's College London, Bessemer Road, London SE5 9PJ, UK.
Aziz U
AU
Momin
Narbeh
N
Melikian
Ajay M
AM
Shah
David J
DJ
Grieve
Stephen B
SB
Wheatcroft
Lindsay
L
John
Ahmed
A
El Gamel
Jatin B
JB
Desai
Toby
T
Nelson
Catherine
C
Driver
Roy A
RA
Sherwood
Mark T
MT
Kearney
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003324:Coronary Artery Disease / Q000097:blood / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D020738:Leptin / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D008323:Mammary Arteries / Q000187:drug effects* / Q000502:physiology; D008875:Middle Aged; D009569:Nitric Oxide; D009765:Obesity / Q000097:blood / Q000503:physiopathology; D012501:Saphenous Vein / Q000187:drug effects* / Q000502:physiology; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology*
D020738:Leptin; D014665:Vasodilator Agents; D009569:Nitric Oxide