Folic Acid Does Not Limit Endothelial Dysfunction Induced by Ischemia and Reperfusion

Dragoni, Saverio; Gori, Tommaso; Stolfo, Giuseppe Di; Sicuro, Silvia; Forconi, S; Parker, John D.

doi:10.1097/01.fjc.0000177983.68563.d1

Cited by 15 publications

(11 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Radial artery diameter and radial artery blood flow returned to baseline values 15 min after local IR ( (10,12,14,15). Reproducing previous findings from our laboratory, rosuvastatin administration prevented the impairment in FMD associated with IR ( Fig.…”

Section: Acute Administration Protocolsupporting

confidence: 85%

Loss of the preconditioning effect of rosuvastatin during sustained therapy: a human in vivo study

Liuni

Luca

Gori

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

Self Cite

View full text Add to dashboard Cite

Studies have demonstrated that the acute administration of 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors has protective effects in the setting of ischemia-reperfusion (IR). Previously, we demonstrated that a single dose of rosuvastatin prevented IR-induced endothelial dysfunction in humans through a cyclooxygenase-2-dependent mechanism. Whether the chronic administration of HMG-CoA reductase inhibitors provides similar protection remains controversial and is unknown in humans. Eighteen male volunteers were randomized to receive a single dose of rosuvastatin (20 mg) or placebo. Twenty-four hours later, endothelium-dependent, radial artery flow-mediated dilation (FMD) was measured before and after IR (15 min of upper arm ischemia followed by 15 min of reperfusion). In a separate protocol, 30 healthy volunteers were randomized in a double-blind fashion to receive oral rosuvastatin (20 mg/day) and placebo, rosuvastatin, and celecoxib (100 mg bid) or placebo alone, all for 21 days. Twenty-four hours after the final administration of study medication, FMD was measured before and after IR. Pre-IR FMD was similar between groups in both protocols. In the acute administration protocol, rosuvastatin significantly prevented the blunting of FMD associated with IR (FMD pre-IR: 8.4 ± 1.3%; post-IR: 6.2 ± 1.3%; P = 0.01 ANOVA, treatment group interaction). In the daily administration protocol, IR significantly blunted FMD in the placebo group (FMD pre-IR: 7.5 ± 0.9%; post-IR: 3.3 ± 0.7%; P < 0.001). Chronic treatment with rosuvastatin did not modify this ischemic injury (FMD pre-IR: 6.9 ± 0.4%; post-IR: 1.6 ± 1.0%; P < 0.001; P = NS ANOVA, treatment group interaction). Similarly, FMD responses post-IR in volunteers receiving rosuvastatin and celecoxib did not significantly differ from placebo (FMD pre-IR: 8.3 ± 0.9%; post-IR: 2.1 ± 0.8%; P < 0.001; P = NS ANOVA, treatment group interaction). In contrast to acute administration, chronic rosuvastatin does not prevent the development of IR-induced endothelial dysfunction in normal humans.

show abstract

Section: Acute Administration Protocolsupporting

confidence: 85%

Loss of the preconditioning effect of rosuvastatin during sustained therapy: a human in vivo study

Liuni

Luca

Gori

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

Self Cite

View full text Add to dashboard Cite

show abstract

“…L-Citrulline is a urea cycle intermediate metabolized to arginine by a recycling pathway consisting of two enzymes, argininosuccinate synthase (AS) and argininosuccinate lyase (AL). These two enzymes, AS and AL, have been found colocated with eNOS in pulmonary endothelial cells (7). It is thought that together these enzymes produce a separate subcellular pool of arginine used exclusively for NO synthesis.…”

Section: Discussionmentioning

confidence: 99%

l-Citrulline ameliorates chronic hypoxia-induced pulmonary hypertension in newborn piglets

Ananthakrishnan

Barr²,

Summar³

et al. 2009

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

Newborn piglets develop pulmonary hypertension and have diminished pulmonary vascular nitric oxide (NO) production when exposed to chronic hypoxia. NO is produced by endothelial NO synthase (eNOS) in the pulmonary vascular endothelium using l-arginine as a substrate and producing l-citrulline as a byproduct. l-Citrulline is metabolized to l-arginine by two enzymes that are colocated with eNOS in pulmonary vascular endothelial cells. The purpose of this study was to determine whether oral supplementation with l-citrulline during exposure of newborn piglets to 10 days of chronic hypoxia would prevent the development of pulmonary hypertension and increase pulmonary NO production. A total of 17 hypoxic and 17 normoxic control piglets were studied. Six of the 17 hypoxic piglets were supplemented with oral l-citrulline starting on the first day of hypoxia. l-Citrulline supplementation was provided orally twice a day. After 10 days of hypoxia or normoxia, the animals were anesthetized, hemodynamic measurements were performed, and the lungs were perfused in situ. Pulmonary arterial pressure and pulmonary vascular resistance were significantly lower in hypoxic animals treated with l-citrulline compared with untreated hypoxic animals (P < 0.001). In vivo exhaled NO production (P = 0.03) and nitrite/nitrate accumulation in the perfusate of isolated lungs (P = 0.04) were significantly higher in l-citrulline-treated hypoxic animals compared with untreated hypoxic animals. l-Citrulline supplementation ameliorated the development of pulmonary hypertension and increased NO production in piglets exposed to chronic hypoxia. We speculate that l-citrulline may benefit neonates exposed to prolonged periods of hypoxia from cardiac or pulmonary causes.

show abstract

“…The methods for the assessment of FMD in our laboratory, as well as the repeatability of measurements, have been previously described in detail (11,12,17,18,20). Briefly, end-diastolic, ECG-gated, longitudinal, B-mode images of the artery 10 -15 cm below the antecubital fossa were digitally acquired and stored for off-line analysis.…”

Section: Flow-mediated Dilation (Fmd) Is a Noninvasive Techniquementioning

confidence: 99%

Observations of time-based measures of flow-mediated dilation of forearm conduit arteries: implications for the accurate assessment of endothelial function

Liuni

Luca

Lisi

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

Self Cite

View full text Add to dashboard Cite

dependent flow-mediated dilation (FMD) is measured as the increase in diameter of a conduit artery in response to reactive hyperemia, assessed either at a fixed time point [usually 60-s post-cuff deflation (FMD60)] or as the maximal dilation during a 5-min continuous, ECG-gated, measurement (FMDmax-cont). Preliminary evidence suggests that the time between reactive hyperemia and peak dilation (time to FMDmax) may provide an additional index of endothelial health. We measured FMDmax-cont, FMD60, and time to FMDmax in 30 young healthy volunteers, 22 healthy middle-aged adults, 16 smokers, 23 patients with hypertension, 40 patients with coronary artery disease, and 22 patients with heart failure. As previously reported, FMDmax-cont was similar in healthy cohorts and was significantly blunted in smokers and all patient groups, whereas FMD60 was significantly blunted only in heart failure patients. There was a wide within-group variability between measures of time to FMDmax with no significant difference between normal and patient groups. Intra-arterial infusion of the nitric oxide synthase inhibitor N -monomethyl-L-arginine in eight healthy subjects resulted in a blunting of FMDmax-cont (P Ͻ 0.001) and FMD60 (P ϭ 0.02) but not time to FMDmax. Both FMDmax-cont and FMD60 demonstrated good repeatability in 30 young healthy volunteers studied on two separate occasions (P Ͻ 0.01 for both), whereas time to FMD max varied widely between visits (P ϭ not significant). In conclusion, although time to FMDmax does not appear to be a useful adjunctive measure of endothelial health, the use of continuous diameter measurements provides important data in the study of endothelial function in healthy subjects and patients with cardiovascular disease. endothelium; vascular physiology; flow-mediated dilation; arterial diameter; time to peak dilation FLOW-MEDIATED DILATION (FMD) is a noninvasive technique used to evaluate the function of the vascular endothelium in peripheral conduit arteries. The concept of FMD is based on the observation that the induction of ischemia in a peripheral limb (usually the hand/forearm), followed by rapid deflation of the pneumatic cuff used to induce this ischemia, causes a sudden increase in blood flow (reactive hyperemia) in the conduit artery that provides blood to this territory. The ensuing sudden change in local shear stress causes an endotheliumdependent production of a number of vasoactive substances, including nitric oxide (NO) (5, 7). Since the ability of the vessel to respond to changes in shear stress is dependent on an intact and healthy endothelium, the magnitude of this flowinduced vasodilatory response has been proposed as a surrogate measure of overall endothelial function. Importantly, FMD of the radial artery has been demonstrated to be mediated primarily by NO, such that the response observed can also indicate the degree of NO bioavailability (23), although this concept has been recently challenged (26).Traditionally, FMD is calculated as the dilation induced by reactive hyperemia, exp...

show abstract

Folic Acid Does Not Limit Endothelial Dysfunction Induced by Ischemia and Reperfusion

Cited by 15 publications

References 30 publications

Loss of the preconditioning effect of rosuvastatin during sustained therapy: a human in vivo study

Loss of the preconditioning effect of rosuvastatin during sustained therapy: a human in vivo study

l-Citrulline ameliorates chronic hypoxia-induced pulmonary hypertension in newborn piglets

Observations of time-based measures of flow-mediated dilation of forearm conduit arteries: implications for the accurate assessment of endothelial function

Contact Info

Product

Resources

About