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Effect of mTOR Antagonism on Endothelial Function in the Human Cutaneous Vasculature (LB699)
Author(s) -
Kellogg Dean,
Zhao Joan,
Wu Yubo,
Roman Linda
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.lb699
Subject(s) - vasodilation , medicine , sodium nitroprusside , microdialysis , pharmacology , endocrinology , nitric oxide , central nervous system
Inhibition of the mechanistic Target of Rapamycin (mTOR) for 1 week causes endothelial dysfunction in rodents. We hypothesized that a similar effect would be observed in humans. 4 middle‐aged persons participated. mTOR was antagonized by topical application of 8% rapamycin (RAPA) ointment to skin. RAPA was applied twice daily for 7 days to an 8x8 cm area of skin on the abdomen while the ointment vehicle only was applied to a second untreated control site. We examined the effect of these treatments on skin blood flow (SkBF) vasodilatory responses to 5 increasing doses of methacholine (MCH) given by intradermal microdialysis. Responses were monitored by laser‐Doppler flowmetry (LDF) at the RAPA treated and untreated control sites. After delivering the 5 MCH doses, 58mM nitroprusside (SNP) was given at both sites to effect maximal vasodilation for data normalization (%maxLDF). Results: At baselines and in response to MCH doses of 10microM, 100microM, 1mM, and 100mM no differences were found between responses at RAPA and control sites. At 10mM MCH, the vasodilation at RAPA treated sites exceeded that at untreated sites (RAPA 85±6 vs Control 68±9%maxLDF, p<0.05). Absolute value (mV) responses to SNP did not differ between RAPA and vehicle treated sites (p>0.05). We conclude that chronic RAPA treatment improves endothelium dependent vasodilation in middle‐aged persons in contrast to causing endothelial dysfunction in rodents. (supported by NIH Grant AG041365) Grant Funding Source : NIA