Abstract
Evidence supports the hypothesis that elevated nonesterified fatty acids (NEFAs) in patients with insulin resistance, eg, obese hypertensive subjects, contribute to increased vascular alpha-adrenergic reactivity and tone by impairing endothelium-dependent vasodilation. To generate further support for this notion, we studied responses to endothelium-dependent and independent dilators under control (0.9% NaCl/heparin) conditions in one hand and with elevated NEFAs in the contralateral hand (10% intralipid/heparin). To observe venodilator responses, the dorsal hand vein diameter was first reduced by approximately 60% with phenylephrine. Studies were repeated with indomethacin to block the generation of cyclooxygenase products. In contrast to previous in vitro data, elevating NEFAs locally in vivo augmented rather than suppressed venodilator responses to the two endothelium-dependent dilators acetylcholine and methacholine (P<.05). Responses to the endothelium-independent dilator nitroglycerin were unaffected. Indomethacin attenuated the capacity of intralipid/heparin to enhance endothelium-dependent dilator responses to acetylcholine and methacholine. Indomethacin did not affect venodilator responses to nitroglycerin. The effect of intralipid/heparin to significantly reduce the phenylephrine infusion rate required to reduce hand vein diameter by approximately 60% was reversed by indomethacin. These data indicate that raising fatty acids locally augments endothelium-dependent dilation by a cyclooxygenase-dependent mechanism. The findings also suggest that NEFAs augment alpha-adrenoceptor-mediated constriction in hand veins by a cyclooxygenase-dependent mechanism. These hand vein studies do not support the notion that the elevated NEFAs in obese hypertensive patients augment alpha1-adrenoceptor-mediated reactivity by reducing nitric oxide synthesis.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.