Carvedilol improves endothelium-dependent vasodilation in patients with dilated cardiomyopathy.
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Acetylcholine↗
Biomedical subjects
Keigo Nakagawa
Publications and source records attributed to Keigo Nakagawa.
Smoking, endothelial function, and Rho-kinase in humans.
OBJECTIVE: Smoking is associated with endothelial dysfunction and activated Rho-kinase in vascular smooth muscle cells (VSMCs) in humans. The purpose of this study was to elucidate the relationship between endothelial function and Rho-kinase activity in forearm VSMCs in healthy young men. METHODS AND RESULTS: We evaluated the forearm blood flow (FBF) responses to acetylcholine (ACh), fasudil, a Rho-kinase inhibitor, and sodium nitroprusside (SNP) in male smokers (n=10) and nonsmokers (n=14). FBF was measured by using a strain-gauge plethysmography. The vasodilatory effect of ACh was significantly smaller in smokers than that in nonsmokers. The vasodilatory effect of fasudil was significantly greater in smokers than that in nonsmokers. The vasodilatory effects of SNP in the 2 groups were similar. There was a significant correlation between the maximal FBF response to fasudil and that to ACh (r=-0.67; P<0.01). There was no significant correlation between the maximal FBF response to fasudil and that to SNP. The intra-arterial coinfusion of fasudil significantly increased the FBF response to ACh in smokers but not in nonsmokers. There were no significant differences between FBF response to fasudil alone and that in combination with NG-monomethyl-L-arginine in smokers and in nonsmokers. The intra-arterial coinfusion ascorbic acid did not alter the FBF response to fasudil in both groups. CONCLUSIONS: These findings suggest that smoking is involved in not only endothelial dysfunction but also activation of Rho-kinase in VSMCs in forearm circulation, and that there is a significant correlation between endothelial function and Rho-kinase activity in VSMCs.
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
Tetrahydrobiopterin improves aging-related impairment of endothelium-dependent vasodilation through increase in nitric oxide production.
Deficiency of tetrahydrobiopterin (BH4), an essential cofactor for nitric oxide (NO) synthase, decreases NO production and increases reactive oxygen species. The purpose of this study was to elucidate the effects of aging on endothelial function and to determine whether the degree of BH4 deficiency is related to aging and oxidative stress. We evaluated forearm blood flow (FBF) responses to acetylcholine (ACh), an endothelium-dependent vasodilator, and isosorbide dinitrate (ISDN), an endothelium-independent vasodilator, before and after co-infusion of BH4 (500 mg/min) in 37 healthy men (mean age, 41+/-18 yr; range, 19-81 yr). FBF was measured using strain-gauge plethysmograph. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and serum malondialdehyde-modified low-density lipoprotein (MDA-LDL) were measured as indices of oxidative stress. Both ACh and ISDN increased the FBF in a dose-dependent manner in all subjects. Co-infusion of BH4 resulted in a significant increase in ACh-induced vasodilation (from 22.3+/-6.7 to 30.1+/-7.5 mL/min/100 mL tissue, P<0.05). Aging was found to be significantly correlated with ACh-induced vasodilation (r=-0.47, P=0.006), urinary 8-OHdG (r=0.38, P=0.02), serum MDA-LDL (r=0.36, P=0.02), and the change in ACh-induced vasodilation after co-infusion of BH4 (r=0.45, P=0.007). The FBF response to ISDN did not correlate with any parameters. Infusion of N(G)-monomethyl-L-arginine, an NO synthase inhibitor, abolished the BH4-induced enhancement of forearm vasorelaxation evoked by ACh. The increase in FBF after ISDN was not altered by BH4. These findings suggest that a deficiency of BH4 may be involved in the pathogenesis of disturbances in endothelium-dependent vasodilation related to aging through decrease in NO production and increase in oxidative stress.
Acetylcholine↗
The nicorandil-induced vasodilation in humans is inhibited by miconazole.
Nicorandil, N-(2-hydroxyethyl)-nicotinamide nitrate, exerts its vasodilatory effects by opening ATP-sensitive potassium (K-ATP) channels and by acting as the exogenous nitric oxide (NO). It is not clear, however, whether the actions of other endothelium-dependent vasodilators, such as NO, endothelium-derived hyperpolarizing factor (EDHF), and prostaglandins, contribute to nicorandil-induced vasodilation in the vasculature in humans. We evaluated forearm blood flow (FBF) response to intraarterial infusion of nicorandil alone and in the presence of glibenclamide, a K-ATP channel inhibitor, N(G)-monomethyl-L-arginine, an NO synthase inhibitor, indomethacin, a cyclooxygenase inhibitor, or miconazol, a cytochrome P-450 inhibitor, in 24 healthy male subjects. FBF was measured using strain-gauge plethysmography. Infusion of nicorandil significantly increased the FBF response in a dose-dependent manner. Intraarterial infusion of glibenclamide attenuated nicorandil-induced vasodilation (160.9 +/- 21.2% versus 90.2 +/- 19.4%, P < 0.01), and miconazole also attenuated the FBF response to nicorandil (160.9 +/- 21.2% versus 66.1 +/- 9.2%, P < 0.001). N-monomethyl-L-arginine or indomethacin did not alter the FBF response to nicorandil. These findings suggest that nicorandil causes vasodilation in forearm circulation in humans, at least in part through a pathway that is dependent on K-ATP channels and cytochrome P-450, but not on endogenous NO and prostaglandins. EDHF may contribute to nicorandil-induced vasodilation in humans.
Adult↗
Alveolar bone marrow as a cell source for regenerative medicine: differences between alveolar and iliac bone marrow stromal cells.
UNLABELLED: We isolated and expanded BMSCs from human alveolar/jaw bone at a high success rate (70%). These cells had potent osteogenic potential in vitro and in vivo, although their chondrogenic and adipogenic potential was less than that of iliac cells. INTRODUCTION: Human bone marrow stromal cells (BMSCs) have osteogenic, chondrogenic, and adipogenic potential, but marrow aspiration from iliac crest is an invasive procedure. Alveolar BMSCs may be more useful for regenerative medicine, because the marrow can be aspirated from alveolar bone with minimal pain. MATERIALS AND METHODS: In this study, alveolar bone marrow samples were obtained from 41 patients, 6-66 years of age, during the course of oral surgery. BMSCs were seeded and maintained in culture with 10% FBS and basic fibroblast growth factor. In addition, BMSCs were induced to differentiate into osteoblasts, chondrocytes, or adipocytes in appropriate medium. RESULTS AND CONCLUSION: From a small volume (0.1-3 ml) of aspirates, alveolar BMSCs expanded at a success ratio of 29/41 (70%). The success rate decreased with increasing donor age, perhaps because of age-dependent decreases in the number and proliferative capacity of BMSCs. The expanded BMSCs differentiated into osteoblasts under osteogenic conditions in 21-28 days: the mRNA levels of osteocalcin, osteopontin, and bone sialoprotein, along with the calcium level, in alveolar BMSC cultures were similar to those in iliac cultures. However, unlike iliac BMSC, alveolar BMSC showed poor chondrogenic or adipogenic potential, and similar differences were observed between canine alveolar and iliac BMSCs. Subsequently, human alveolar BMSCs attached to beta-tricalcium phosphate were transplanted into immunodeficient mice. In transplants, new bone formed with osteoblasts and osteocytes that expressed human vimentin, human osteocalcin, and human GAPDH. These findings suggest that BMSCs have distinctive features depending on their in vivo location and that alveolar BMSCs will be useful in cell therapy for bone diseases.
Adipocytes↗
Effect of edaravone, a novel free radical scavenger, on endothelium-dependent vasodilation in smokers.
The forearm blood flow (FBF) responses to acetylcholine and to sodium nitroprusside were evaluated before and after administration of edaravone in 10 smokers and 10 nonsmokers. FBF response to acetylcholine was lower in smokers than in nonsmokers. The vasodilatory effects of sodium nitroprusside were similar in both groups. Co-infusion of edaravone increased the FBF response to acetylcholine in smokers, but did not affect the FBF response to acetylcholine in nonsmokers. The administration of N(G)-monomethyl-l-arginine abolished edaravone-induced augmentation of the FBF response to acetylcholine in smokers. The antioxidative agent edaravone increases nitric oxide mediated vasodilation through a decrease in oxidative stress.
Acetylcholine↗
Autologous bone-marrow mononuclear cell implantation improves endothelium-dependent vasodilation in patients with limb ischemia.
BACKGROUND: Patients with limb ischemia were associated with endothelial dysfunction. The purpose of this study was to determine whether autologous bone-marrow mononuclear cell (BM-MNC) implantation improves endothelial dysfunction in patients with limb ischemia. METHODS AND RESULTS: We evaluated the leg blood flow (LBF) response to acetylcholine (ACh), an endothelium-dependent vasodilator, and sodium nitroprusside (SNP), an endothelium-independent vasodilator, before and after BM-MNC implantation in 7 patients with limb ischemia. LBF was measured with a mercury-filled Silastic strain-gauge plethysmograph. The number of BM-MNCs implanted into ischemic limbs was 1.6x10(9)+/-0.3x10(9). The number of CD34+ cells included in the implanted BM-MNCs was 3.8x10(7)+/-1.6x10(7). BM-MNC implantation improved the ankle-brachial pressure index (0.33+/-0.21 to 0.39+/-0.17, P=0.06), transcutaneous oxygen pressure (28.4+/-11.5 to 36.6+/-5.2 mm Hg, P=0.03), and pain-free walking time (0.8+/-0.6 to 2.9+/-2.2 minutes, P=0.02). After BM-MNC implantation, LBF response to ACh was enhanced (19.3+/-6.8 versus 29.6+/-7.1 mL/min per 100 mL; P=0.002). The vasodilatory effect of SNP was similar before and after BM-MNC implantation. CONCLUSIONS: These findings suggest that BM-MNC implantation augments endothelium-dependent vasodilation in patients with limb ischemia.
Acetylcholine↗
Effect of different intensities of exercise on endothelium-dependent vasodilation in humans: role of endothelium-dependent nitric oxide and oxidative stress.
BACKGROUND: Aerobic exercise enhances endothelium-dependent vasodilation in hypertensive patients, patients with chronic heart failure, and healthy individuals. However, it is unclear how the intensity of exercise affects endothelial function in humans. The purpose of the present study was to determine the effects of different intensities of exercise on endothelium-dependent vasodilation in humans. METHODS AND RESULTS: We evaluated the forearm blood flow responses to acetylcholine, an endothelium-dependent vasodilator, and isosorbide dinitrate, an endothelium-independent vasodilator, before and after different intensities of exercise (mild, 25% VO2max; moderate, 50% VO2max; and high, 75% VO2max; bicycle ergometers, 30 minutes, 5 to 7 times per week for 12 weeks) in 26 healthy young men. Forearm blood flow was measured using a mercury-filled Silastic strain-gauge plethysmograph. Twelve weeks of moderate-intensity exercise, but not mild- or high-intensity exercise, significantly augmented acetylcholine-induced vasodilation (7.5+/-2.4 to 11.4+/-5.8 mL/min per 100 mL tissue; P<0.05). No intensity of aerobic exercise altered isosorbide dinitrate-induced vasodilation. The administration of NG-monomethyl-L-arginine, a nitric oxide synthase inhibitor, abolished the moderate-intensity exercise-induced augmentation of the forearm blood flow response to acetylcholine. High-intensity exercise increases plasma concentrations of 8-hydroxy-2'-deoxyguanosine (from 6.7+/-1.1 to 9.2+/-2.3 ng/mL; P<0.05) and serum concentrations of malondialdehyde-modified low-density lipoprotein (from 69.0+/-19.5 to 82.4+/-21.5 U/L; P<0.05), whereas moderate exercise tended to decrease both indices of oxidative stress. CONCLUSIONS: These findings suggest that moderate-intensity aerobic exercise augments endothelium-dependent vasodilation in humans through the increased production of nitric oxide and that high-intensity exercise possibly increases oxidative stress.
Acetylcholine↗
Low body mass index is a risk factor for impaired endothelium-dependent vasodilation in humans: role of nitric oxide and oxidative stress.
OBJECTIVES: The purpose of this study was to evaluate the relationship between body mass index (BMI), including low BMIs, and endothelial function. BACKGROUND: Epidemiologic study has demonstrated that not only obesity but also a low BMI may be a risk factor for cardiovascular disease. METHODS: The forearm blood flow (FBF) response to acetylcholine (ACh) and isosorbide dinitrate (ISDN) was measured in 87 healthy young men (15 low BMI, 51 normal, 14 obese, and 7 extremely obese). RESULTS: Plasma concentrations of 8-hydroxy-2'-deoxyguanosine and serum concentrations of malondialdehyde-modified low-density lipoprotein were higher in low BMI, obese, and extremely obese subjects than in normal subjects and were similar among the low BMI, obese, and extremely obese groups. The FBF response to ACh was greater in the normal group than in the other groups (p < 0.001), and was lower in the extremely obese group as compared with the other groups (p < 0.001). The ACh-stimulated vasodilation was similar between the low BMI group and the obese group. The ISDN-stimulated vasodilation was similar in all four groups. There were no significant differences in ACh-stimulated vasodilation between the four groups after the nitric oxide (NO) synthase inhibitor NG-monomethyl-L-arginine infusion. Co-infusion of vitamin C augmented the FBF response to ACh in low BMI, obese, and extremely obese groups--but not in normal BMI group. CONCLUSIONS: These findings suggest that not only obesity but also a low BMI may be a risk factor for impaired endothelium-dependent vasodilation through the increased oxidative stress, leading to the reduced bioavailability of NO.
Acetylcholine↗
Comparison of forearm endothelial function between premenopausal and postmenopausal women with or without hypercholesterolemia.
We sought to determine whether menopausal status or postmenopausal hypercholesterolemia affects forearm resistance artery endothelial function. We studied the forearm resistance artery endothelial function in 75 Japanese women: 25 premenopausal volunteers, 25 postmenopausal women with normal serum low-density lipoprotein (LDL) cholesterol concentrations, and 25 hypercholesterolemic postmenopausal women. Excluded from the study were patients with hypertriglyceridemia, hypertension, or diabetes, cigarette smokers. The forearm blood flow (FBF) during reactive hyperemia and after sublingual nitroglycerin (NTG) administration was measured by strain-gauge plethysmography. The serum concentrations of lipoprotein (a) [Lp(a)] were significantly higher in the hypercholesterolemic postmenopausal group than in the other two groups (P<0.01). These lipid parameters were similar between the premenopausal and postmenopausal women with normal cholesterol. The FBF responses to reactive hyperemia were significantly lower in the postmenopausal hypercholesterolemic women than in the other two groups (P<0.01). The reactive hyperemia also was impaired in the postmenopausal group with normal cholesterol as compared with the premenopausal group (P<0.01). Increases in FBF after NTG were similar between the three groups. By stepwise multivariate analysis, menopausal status and serum LDL cholesterol was the significant predictor of forearm endothelial function. These findings suggest that reactive hyperemia is impaired in forearm resistance arteries after menopause, especially in postmenopausal women with hypercholesterolemia.
Adult↗
PDE5 inhibitor sildenafil citrate augments endothelium-dependent vasodilation in smokers.
Smoking is associated with endothelial dysfunction. The purpose of this study was to determine the effect of sildenafil, an inhibitor of phosphodiesterase type 5 (PDE5), on endothelial function in smokers. We evaluated the forearm blood flow (FBF) responses to acetylcholine (ACh), an endothelium-dependent vasodilator, and to sodium nitroprusside (SNP), an endothelium-independent vasodilator, before and after oral sildenafil administration (100 mg) with a strain-gauge plethysmograph in 10 young healthy male smokers and 10 young healthy male nonsmokers. FBF response to ACh was lower in smokers than in nonsmokers. The vasodilatory effects of SNP were similar in both groups. Sildenafil increased the FBF response to ACh from 9.3+/-2.0 to 12.5+/-3.5 mL/min per 100 mL tissue in smokers and from 12.6+/-5.6 to 19.6+/-8.4 mL/min per 100 mL tissue in nonsmokers, and it increased the response to SNP from 13.3+/-3.9 to 15.1+/-4.3 mL/min per 100 mL tissue in smokers and from 14.8+/-5.2 to 18.4+/-6.0 mL/min/100 mL tissue in nonsmokers (P<0.05 for all). The ratio of maximal ACh-stimulated FBF expressed as a ratio of maximal SNP-stimulated FBF significantly increased after administration of sildenafil in both groups. Infusion of NG-monomethyl-L-arginine, a nitric oxide synthase inhibitor, abolished sildenafil-induced augmentation of the FBF response to ACh in both groups. The findings suggest that endothelial function is impaired in smokers compared with that in nonsmokers, that inhibition of PDE5 by sildenafil significantly increases nitric oxide-mediated vasodilation, and that the activities of PDE5 in smokers and nonsmokers may be similar.
3',5'-Cyclic-GMP Phosphodiesterases↗
Smoking activates rho-kinase in smooth muscle cells of forearm vasculature in humans.
Previous studies have shown that smoking is strongly associated with atherosclerosis and coronary vascular disease. Rho-kinase plays an important role in various cellular functions associated with atherosclerosis and hypertension. However, there is no information on the relationship between smoking and Rho-kinase activity in humans. The purpose of this study was to determine the Rho-kinase activity in forearm vascular smooth muscle cells (VSMCs) in healthy young male smokers. We evaluated the forearm blood flow (FBF) responses to fasudil (3, 10, and 30 microg/min for 5 minutes), a Rho-kinase inhibitor, or sodium nitroprusside (0.75, 1.5, and 3.0 microg/min for 5 minutes) in current smokers (n=8) and nonsmokers (n=8). FBF was measured with a strain-gauge plethysmograph. The vasodilatory effect of fasudil was significantly greater in smokers than in nonsmokers (14.9+/-3.5 versus 10.5+/-3.6 mL/min per 100 mL tissue; P<0.01). The FBF responses to sodium nitroprusside were similar in the 2 groups (34.7+/-10.4 versus 33.2+/-10.2 mL/min per 100 mL tissue; P=0.78). These findings suggest that smoking activates Rho-kinase in forearm VSMCs but does not alter the vasodilatory effect induced by exogenous nitric oxide in forearm VSMCs in healthy young men.
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
A comparison of low-dose and standard-dose oral estrogen on forearm endothelial function in early postmenopausal women.
We investigated the effects of low-dose estrogen plus progestin on endothelial function. Postmenopausal women received daily doses of conjugated equine estrogen (CEE, 0.625 mg) plus medroxyprogesterone acetate (MPA, 2.5 mg) (standard-dose group, n = 18), CEE (0.3 mg) plus MPA (2.5 mg) (low-dose group, n = 18), or no treatment (control group, n = 15) for 3 months. Serum concentrations of lipids and malondialdehyde (MDA)-modified low-density lipoprotein (LDL) were measured. Forearm blood flow (FBF) during reactive hyperemia and after sublingual nitroglycerin administration was measured by strain-gauge plethysmography. Decreases in serum concentrations of LDL cholesterol and MDA-modified LDL and increases in high-density lipoprotein cholesterol and nitrite/nitrate were observed in both treatment groups. After 3 months of treatment, similar increases in the maximal FBF response during reactive hyperemia were observed in both treatment groups (standard-dose group, from 35.8 +/- 3.0 to 47.5 +/- 2.8 ml/min per 100 ml tissue; and low-dose group, from 35.2 +/- 2.2 to 46.8 +/- 3.4 ml/min per 100 ml tissue, P < 0.01). FBF levels in the control group were unchanged. Treatment did not affect nitroglycerin-induced dilation. The incidences of vaginal bleeding and breast tenderness were lower with the low-dose group than with the standard-dose group. Low-dose CEE plus MPA augments endothelial function in forearm resistance arteries and decreased MDA-modified LDL levels similarly to standard doses of CEE plus MPA, with fewer side effects.
Administration, Oral↗
Leptin causes nitric-oxide independent coronary artery vasodilation in humans.
Recent studies have shown that leptin causes vasodilation. However, it is unclear whether leptin causes coronary vasodilation in humans. To determine how leptin affects human coronary arteries and whether endothelium-derived nitric oxide (EDNO) is involved in the coronary arterial response to leptin, we infused leptin (0.3, 3 and 30 ng/kg/min) for 2 min into the left coronary ostium before and after an infusion of nitric oxide synthase inhibitor, N(G)-monomethyl-L-arginine (L-NMMA), in 11 men with angiographically normal coronary arteries. The diameter of the epicardial coronary arteries was quantitatively measured, and coronary blood flow (CBF) was calculated by quantitative angiography and Doppler flow velocity measurements. The changes in these parameters in response to leptin are expressed as the % change from the baseline values. Leptin caused coronary dilation (0.3 ng/kg/min: 2.0+/-0.5%; 3 ng/kg/min: 4.9+/-0.7%; 30 ng/kg/min: 3.8+/-0.9%) and increased CBF (13.6+/-3.3%, 36.8+/-5.6%, and 39.2+/-7.4%, respectively). After the infusion of L-NMMA, leptin also caused coronary dilation (2.0+/-0.4%, 4.5+/-0.7%, and 4.6+/-0.8%, respectively) and increased CBF (14.6+/-2.8%, 39.2+/-5.7%, 40.3+/-6.2%, respectively). Leptin-induced coronary vasodilation was not affected by the infusion of L-NMMA. These results suggest that leptin dilates coronary arteries in humans. Furthermore, EDNO may not contribute to leptin-induced coronary dilation.
Aged↗
Circadian variation of blood pressure and endothelial function in patients with essential hypertension:a comparison of dippers and non-dippers.
OBJECTIVES: The purpose of this study was to evaluate the relationship between the circadian blood pressure (BP) rhythm and endothelial function in patients with essential hypertension. BACKGROUND: Hypertension is associated with alterations in resistance artery endothelial function. Patients with a non-dipper circadian pattern of BP have a greater risk of cerebrovascular and cardiovascular complications than do patients with a dipper circadian pattern. METHODS: We evaluated the forearm blood flow (FBF) response to intra-arterial acetylcholine (ACh), an endothelium-dependent vasodilator, and isosorbide dinitrate (ISDN), an endothelium-independent vasodilator, infusion in 20 patients with non-dipper hypertension and 20 age- and gender-matched patients with dipper hypertension. The FBF was measured using a mercury-filled Silastic strain-gauge plethysmograph. RESULTS: The 24-h systolic BP, as well as nocturnal systolic and diastolic BPs were higher in non-dipper patients than in dipper patients. The 24-h urinary excretion of nitrite/nitrate and cyclic guanosine monophosphate was lower in non-dippers than in dippers. The response of FBF to ACh was smaller in non-dippers than in dippers (25.1 +/- 3.1 vs. 20.2 +/- 3.0 ml/min/100 ml tissue, p < 0.05). The FBF response to ISDN was similar in dippers and non-dippers. The FBF response to ACh was similar in the two groups following intra-arterial infusion of the nitric oxide (NO) synthase inhibitor N(G)-monomethyl-L-arginine. CONCLUSIONS: These findings suggest that endothelium-dependent vasodilation is blunted through a decrease in NO release in non-dippers compared with patients who have dipper hypertension.
Acetylcholine↗
Endothelial function and oxidative stress in renovascular hypertension.
BACKGROUND: It has been reported that renovascular hypertension activates the renin-angiotensin system, leading to an increase in oxidative stress. We sought to determine whether renal-artery angioplasty improves endothelial dysfunction in patients with renovascular hypertension through a reduction in oxidative stress. METHODS: We evaluated the response of forearm blood flow to acetylcholine, an endothelium-dependent vasodilator, and isosorbide dinitrate, an endothelium-independent vasodilator, before and after renal-artery angioplasty in 15 subjects with renovascular hypertension and 15 controls without hypertension who were matched for age and sex. Forearm blood flow was measured with the use of a mercury-filled Silastic strain-gauge plethysmograph. RESULTS: The forearm blood flow in response to acetylcholine was less in subjects with renovascular hypertension than in controls, although the forearm blood flow in response to isosorbide dinitrate was similar in the two groups. Angioplasty decreased systolic and diastolic blood pressures, forearm vascular resistance, and urinary excretion of 8-hydroxy-2'-deoxyguanosine and serum malondialdehyde-modified low-density lipoprotein (LDL), indexes of oxidative stress. After angioplasty, the mean (+/-SD) forearm blood flow in response to acetylcholine was increased in the patients with renovascular hypertension (19.3+/-6.8 vs. 29.6+/-7.1 ml per minute per 100 ml, P=0.002). The increase in the maximal forearm blood flow in response to acetylcholine correlated significantly with the decrease in urinary excretion of 8-hydroxy-2'-deoxyguanosine (r=-0.51, P=0.004) and serum malondialdehyde-modified LDL (r=-0.39, P=0.02). Coinfusion of ascorbic acid (vitamin C) augmented the response of forearm blood flow to acetylcholine before angioplasty (P<0.001) but not after angioplasty. CONCLUSIONS: These findings suggest that excessive oxidative stress is involved, at least in part, in impaired endothelium-dependent vasodilatation in patients with renovascular hypertension.
8-Hydroxy-2'-Deoxyguanosine↗
Tetrahydrobiopterin enhances forearm vascular response to acetylcholine in both normotensive and hypertensive individuals.
BACKGROUND: A deficiency of tetrahydrobiopterin (BH4), an essential cofactor for nitric oxide (NO) synthase, decreases NO synthesis and increases superoxide production. Supplementation of BH4 has been postulated to improve endothelial function in atherosclerotic patients. The purpose of this study was to determine whether BH4 restores endothelium-dependent vasodilation in patients with essential hypertension. METHODS: We evaluated the effects of BH4 on forearm vascular responses to acetylcholine (ACh), an endothelium-dependent vasodilator, and isosorbide dinitrate (ISDN), an endothelium-independent vasodilator, both in patients with essential hypertension and in age- and sex-matched normal control subjects. Forearm blood flow (FBF) was measured using strain gauge plethysmography. RESULTS: The response of FBF to ACh was less in hypertensive patients (n = 8) than in normal control subjects (n = 8). There was no significant difference in FBF response to ISDN in the two groups. During coinfusion of BH4 (500 mg/min), the FBF response to ACh in hypertensive patients increased significantly (14.8 +/- 4.6 to 25.6 +/- 7.3 mL/min/100 mL tissue, P < .05) to the level of normal control subjects. In the control subjects, also, BH4 augmented the FBF response to ACh (27.8 +/- 8.7 to 36.1 +/- 9.6 mL/min/100 mL tissue, P < .05). The increase in FBF after ISDN was not altered by BH4 in either group (each group, n = 6). CONCLUSION: Supplementation of BH4 augments endothelium-dependent vasodilation in both normotensive and hypertensive individuals.
Acetylcholine↗
A low-calorie diet improves endothelium-dependent vasodilation in obese patients with essential hypertension.
BACKGROUND: Both obesity and hypertension are associated with endothelial dysfunction. The purpose of this study was to investigate the effects of a low-calorie diet on endothelial function in obese patients with essential hypertension. METHODS: We measured forearm blood flow (FBF) during intra-arterial infusion of acetylcholine (ACh; 7.5, 15, 30 microg/min), an index of endothelium-dependent vasodilation, and isosorbide dinitrate (ISDN; 0.75, 1.5, 3.0 microg/min), an index of endothelium-independent vasodilation, in obese patients with essential hypertension before and after 2 weeks on a low-calorie diet (800 kcal/d). The study included 11 obese hypertensive Japanese patients (mean body mass index, 30.8 +/- 3.6 kg/m2). Fifteen healthy Japanese normotensive individuals were recruited as a control group. RESULTS: In obese patients with hypertension, the response of FBF to ACh was attenuated compared to healthy individuals (P < .001). Caloric restriction reduced body weight from 77.5 +/- 15.0 to 73.2 +/- 13.5 kg (P < .01), the mean blood pressure from 118.4 +/- 8.7 to 105.7 +/- 8.5 mm Hg (P < .01), fasting plasma insulin from 85.8 +/- 22.8 to 64.8 +/- 27.0 pmol/L (P < .05), serum total cholesterol from 5.30 +/- 0.76 to 4.67 +/- 0.58 mmol/L (P < .05), and low density lipoprotein cholesterol from 3.80 +/- 0.48 to 3.29 +/- 0.44 mmol/L (P < .05). Basal FBF was similar before and after weight reduction. Caloric restriction enhanced the response of FBF to ACh (P < .05), but did not alter the response to ISDN. The intra-arterial infusion of NG-monomethyl-L-arginine (8 micromol/min), a nitric oxide synthase inhibitor, decreased the enhanced ACh-induced blood flow response induced by caloric restriction. CONCLUSIONS: The present findings suggest that the caloric restriction improves endothelial-dependent vasodilation through an increased release of nitric oxide in obese hypertensive patients.
Acetylcholine↗