Abstract-The purpose of this study was to evaluate endothelial function in patients with periodontitis. We evaluated forearm blood flow responses to acetylcholine and sodium nitroprusside in patients with periodontitis who had no other cardiovascular risk factors (32 men; 25Ϯ3 years of age), in a normal control group (20 men; 26Ϯ3 years of age), and in hypertensive patients with periodontitis (28 men and 10 women; 56Ϯ12 years of age) and without periodontitis (control group; 18 men and 6 women; 54Ϯ13 years of age). Forearm blood flow was measured using strain-gauge plethysmography. Circulating levels of C-reactive protein and interleukin-6 were significantly higher in the periodontitis group than in the control group. Both in healthy and hypertensive subjects, forearm blood flow responses to acetylcholine were significantly smaller in the periodontitis group than in the control group. Sodium nitroprussidestimulated vasodilation was similar in the 2 groups. Periodontal therapy reduced serum concentrations of C-reactive protein and interleukin-6 and augmented acetylcholine-induced vasodilation in periodontitis patients with and without hypertension. After administration of N G -monomethyl-L-arginine, an NO synthase inhibitor, forearm blood flow response to acetylcholine was similar before and after treatment. These findings suggest that periodontitis is associated with endothelial dysfunction in subjects without cardiovascular risk factors, as well as hypertensive patients, through a decrease in NO bioavailability and that systemic inflammation may be, at least in part, a cause of endothelial dysfunction, leading to cardiovascular diseases.

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 endotheliumdependent 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 1.6ϫ10 9 Ϯ0.3ϫ10 9 . The number of CD34 ϩ cells included in the implanted BM-MNCs was 3.8ϫ10 7 Ϯ1.6ϫ10 7 . BM-MNC implantation improved the ankle-brachial pressure index (0.33Ϯ0.21 to 0.39Ϯ0.17, Pϭ0.06), transcutaneous oxygen pressure (28.4Ϯ11.5 to 36.6Ϯ5.2 mm Hg, Pϭ0.03), and pain-free walking time (0.8Ϯ0.6 to 2.9Ϯ2.2 minutes, Pϭ0.02). After BM-MNC implantation, LBF response to ACh was enhanced (19.3Ϯ6.8 versus 29.6Ϯ7.1 mL/min per 100 mL; Pϭ0.002). 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.

Background-Several studies have shown that both early and late effects of ischemic preconditioning (IPC) protect against myocardial injury after ischemic reperfusion. Methods and Results-The purpose of this study was to evaluate the late effects of IPC on endothelial function in humans.Late phase of IPC was induced by upper limb ischemia (cuff inflation of over 200 mm Hg for 5 minutes) 6 times a day for 1 month. We evaluated forearm blood flow (FBF) responses to acetylcholine (ACh) and to sodium nitroprusside (SNP) before and after IPC stimulus in 30 young healthy men. FBF was measured using a strain-gauge plethysmograph. The IPC stimulus significantly increased plasma concentration of vascular endothelial growth factor (VEGF), circulating level of endothelial progenitor cells (EPCs), and FBF responses to ACh, but these did not change in the control group. The FBF responses to SNP were similar before and after the IPC stimulus. Infusion of N G -monomethyl-L-arginine, a nitric oxide synthase inhibitor, completely eliminated the IPC stimulus-induced augmentation of FBF responses to ACh. In the cotralateral arms of subjects that received the IPC stimulus, FBF responses to ACh did not change, but levels of VEGF and circulating EPCs increased. Conclusions-These findings suggest that repetition of late IPC stimulus augments endothelium-dependent vasodilation in humans through increases in nitric oxide production and number of EPCs under a local condition. Repetition of IPC stimulus may be a simple, safe, and feasible therapeutic technique for endothelial protection of peripheral vessels.

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