| Autor: |
Trinity JD; Geriatric Research, Education, and Clinical Center, Department of Veterans Affairs Medical Center, Salt Lake City, Utah.; Department of Internal Medicine, University of Utah, Salt Lake City, Utah.; Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, Utah., Kwon OS; Department of Internal Medicine, University of Utah, Salt Lake City, Utah.; Department of Kinesiology, University of Connecticut, Storrs, Connecticut., Broxterman RM; Geriatric Research, Education, and Clinical Center, Department of Veterans Affairs Medical Center, Salt Lake City, Utah.; Department of Internal Medicine, University of Utah, Salt Lake City, Utah., Gifford JR; Geriatric Research, Education, and Clinical Center, Department of Veterans Affairs Medical Center, Salt Lake City, Utah.; Department of Exercise Science, Brigham Young University, Provo, Utah., Kithas AC; Department of Internal Medicine, University of Utah, Salt Lake City, Utah., Hydren JR; Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, Utah., Jarrett CL; Geriatric Research, Education, and Clinical Center, Department of Veterans Affairs Medical Center, Salt Lake City, Utah., Shields KL; Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, Utah., Bisconti AV; Department of Internal Medicine, University of Utah, Salt Lake City, Utah., Park SH; Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, Utah., Craig JC; Department of Internal Medicine, University of Utah, Salt Lake City, Utah., Nelson AD; Department of Internal Medicine, University of Utah, Salt Lake City, Utah., Morgan DE; Department of Anesthesiology, University of Utah, Salt Lake City, Utah., Jessop JE; Department of Anesthesiology, University of Utah, Salt Lake City, Utah., Bledsoe AD; Department of Anesthesiology, University of Utah, Salt Lake City, Utah., Richardson RS; Geriatric Research, Education, and Clinical Center, Department of Veterans Affairs Medical Center, Salt Lake City, Utah.; Department of Internal Medicine, University of Utah, Salt Lake City, Utah.; Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, Utah. |
| Abstrakt: |
Passive leg movement (PLM) evokes a robust and predominantly nitric oxide (NO)-mediated increase in blood flow that declines with age and disease. Consequently, PLM is becoming increasingly accepted as a sensitive assessment of endothelium-mediated vascular function. However, a substantial PLM-induced hyperemic response is still evoked despite nitric oxide synthase (NOS) inhibition. Therefore, in nine young healthy men (25 ± 4 yr), this investigation aimed to determine whether the combination of two potent endothelium-dependent vasodilators, specifically prostaglandin (PG) and endothelium-derived hyperpolarizing factor (EDHF), account for the remaining hyperemic response to the two variants of PLM, PLM (60 movements) and single PLM (sPLM, 1 movement), when NOS is inhibited. The leg blood flow (LBF, Doppler ultrasound) response to PLM and sPLM following the intra-arterial infusion of N G -monomethyl-l-arginine (l-NMMA), to inhibit NOS, was compared to the combined inhibition of NOS, cyclooxygenase (COX), and cytochrome P -450 (CYP450) by l-NMMA, ketorolac tromethamine (KET), and fluconazole (FLUC), respectively. NOS inhibition attenuated the overall LBF [area under the curve (LBF AUC )] response to both PLM (control: 456 ± 194, l-NMMA: 168 ± 127 mL, P < 0.01) and sPLM (control: 185 ± 171, l-NMMA: 62 ± 31 mL, P = 0.03). The combined inhibition of NOS, COX, and CYP450 (i.e., l-NMMA+KET+FLUC) did not further attenuate the hyperemic responses to PLM (LBF AUC : 271 ± 97 mL, P > 0.05) or sPLM (LBF AUC : 72 ± 45 mL, P > 0.05). Therefore, PG and EDHF do not collectively contribute to the non-NOS-derived NO-mediated, endothelium-dependent hyperemic response to either PLM or sPLM in healthy young men. These findings add to the mounting evidence and understanding of the vasodilatory pathways assessed by the PLM and sPLM vascular function tests. NEW & NOTEWORTHY Passive leg movement (PLM) evokes a highly nitric oxide (NO)-mediated hyperemic response and may provide a novel evaluation of vascular function. The contributions of endothelium-dependent vasodilatory pathways, beyond NO and including prostaglandins and endothelium-derived hyperpolarizing factor, to the PLM-induced hyperemic response to PLM have not been evaluated. With intra-arterial drug infusion, the combined inhibition of nitric oxide synthase (NOS), cyclooxygenase, and cytochrome P -450 (CYP450) pathways did not further diminish the hyperemic response to PLM compared with NOS inhibition alone. |
