Background-Several nonpharmacological interventions, including exercise, are recommended in primary prevention of hypertension and other cardiovascular diseases in which the pathogenetic role of endothelial dysfunction has been suggested. We studied the effects of long-term aerobic exercise on endothelial function in patients with essential hypertension. Methods and Results-The forearm blood flow was measured by strain-gauge plethysmography. The responses of forearm vasculature to acetylcholine were smaller in the hypertensive patients than in the normotensive subjects. There was no significant difference in forearm vascular responses to isosorbide dinitrate in the normotensive and hypertensive subjects. We evaluated the effects of physical exercise for 12 weeks on forearm hemodynamics in untreated patients with mild essential hypertension who were divided randomly into an exercise group (nϭ10) and a control group (nϭ7). After 12 weeks, the forearm blood flow response to acetylcholine increased significantly, from 25.8Ϯ9.8 to 32.3Ϯ11.2 mL ⅐ min Ϫ1 ⅐ 100 mL tissue Ϫ1 (PϽ0.05), in the exercise group but not in the control group. The increase in the forearm blood flow after isosorbide dinitrate was similar before and after 12 weeks of follow-up in both groups. The infusion of N G -monomethyl-L-arginine abolished the exercise-induced enhancement of forearm vasorelaxation evoked by acetylcholine in the exercising group. In normotensive subjects also, long-term aerobic exercise augmented acetylcholine-stimulated nitric oxide release. Conclusions-These findings suggest that long-term physical exercise improves endothelium-dependent vasorelaxation through an increase in the release of nitric oxide in normotensive as well as hypertensive subjects. (Circulation. 1999;100:1194-1202.)

Eradication of H. pylori increased the prevalence of reflux oesophagitis in our patient group. The presence of hiatal hernia and corpus gastritis are closely related to the development of reflux oesophagitis after H. pylori eradication therapy.

These findings suggest that ACE inhibitors augment reactive hyperemia, an index of endothelium-dependent vasorelaxation, in patients with essential hypertension. This augmentation may be due to increases in NO.

A clinicopathological analysis of the risk factors for lymph node metastasis was performed in 177 patients with submucosal invasive colorectal carcinoma (CRC). The submucosal deepest invasive portion was histologically subclassified as well (W), moderately (M), or poorly (Por) differentiated. M type was further subdivided into moderately-well (Mw) and moderately-poorly (Mp) differentiated. The pattern of tumor growth was classified as polypoid growth (PG) and non-polypoid growth (NPG). Lymph node metastasis was detected in 21 (12%) of the 177 patients. Macroscopically, type IIc and IIa + IIc lesions showed a significantly higher incidence of lymph node metastasis (44% and 30%) than type IIa and I (4% and 8%). Regarding the histologic subclassification, Por and Mp lesions showed a significantly higher incidence of lymph node metastasis (67% and 37%) than W and Mw lesions (4% and 14%). NPG tumors showed a significantly higher incidence of lymph node metastasis (29%) than PG tumors (7%). The depth of submucosal invasion and lymphatic invasion (ly) were also significantly correlated with the incidence of lymph node metastasis (submucosal scanty (sm-s) invasion 4%, massive invasion 20%; ly(+) 23%, ly(-) 5%). None of the lesions with both sm-s invasion and of W or Mw type showed lymph node metastasis. These results indicate that submucosal invasive CRC with both sm-s invasion and of W or Mw type, which shows no ly, is the appropriate indication for endoscopic curative treatment.

The effects of long-term aerobic exercise on endothelial function in patients with essential hypertension remain unclear. To determine whether endothelial function relating to forearm hemodynamics in these patients differs from normotensive subjects and whether endothelial function can be modified by continued physical exercise, we randomized patients with essential hypertension into a group that engaged in 30 minutes of brisk walking 5 to 7 times weekly for 12 weeks (n20) or a group that underwent no activity modifications (control group, n7). Forearm blood flow was measured using strain-gauge plethysmography during reactive hyperemia to test for endothelium-dependent vasodilation and after sublingual nitroglycerin administration to test endothelium-independent vasodilation. Forearm blood flow in hypertensive patients during reactive hyperemia was significantly less than that in normotensive subjects (n17). Increases in forearm blood flow after nitroglycerin were similar between hypertensive and normotensive subjects. Exercise lowered mean blood pressure from 115.75.3 to 110.25.1 mm Hg (P0.01) and forearm vascular resistance from 25.63.2 to 23.22.8 mm Hg/mL per minute per 100 mL tissue (P0.01); no change occurred in controls. Basal forearm blood flow, body weight, and heart rate did not differ with exercise. After 12 weeks of exercise, maximal forearm blood flow response during reactive hyperemia increased significantly, from 38.44.6 to 47.14.9 mL/min per 100 mL tissue (P0.05); this increase was not seen in controls. Changes in forearm blood flow after sublingual nitroglycerin administration were similar before and after 12 weeks of exercise. Intra-arterial infusion of the nitric oxide synthase inhibitor N G-monomethyl-L-arginine abolished the enhancement of reactive hyperemia induced by 12 weeks of exercise. These findings suggest that through increased release of nitric oxide, continued physical exercise alleviates impairment of reactive hyperemia in patients with essential hypertension. (Hypertension. 1999;33[part II]:591-597.) Key Words: exercise, aerobic hyperemia, reactive nitroglycerin nitric oxide N G-monomethyl-L-arginine endothelium hypertension, essential R egular aerobic exercise by patients with essential hyper-tension is associated with beneficial changes in blood pressure, lipoprotein profile, glucose metabolism, and neuro-hormonal release. Recent epidemiological studies have shown that physical exercise reduces cardiovascular morbidity and mortality in the general population, including individuals with hypertension. 1,2 However, the mechanism underlying antihypertensive and antiatherogenic effects of exercise remains unclear. Several lines of evidence indicate impairment of endothe-lium-dependent vasorelaxation in the vessels of the forearm 3,4 and in the coronary 5 and renal 6,7 circulation of patients with essential hypertension. Recent experiments have demonstrated that continued exercise augmented vasodilation evoked by the endothelium-dependent vasodilator acetylcho-line in dogs 8 and rats,...