Abstract-Angiotensin-(1-7) has been suggested to be a novel vasodilating peptide. We investigated the direct vascular effect of angiotensin-(1-7) in human forearm resistant vessels, particularly with regard to the interaction with angiotensin II, in healthy normotensive men by strain-gauge venous occlusion plethysmography with intra-arterial infusions of peptides. Intra-arterial infusion of angiotensin-(1-7) at 0.1 to 2000 pmol/min did not cause vasodilatation but rather reduced forearm blood flow by Ϸ10% at the highest dose. A placebo-controlled study showed that angiotensin-(1-7) at 0.5 to 40 nmol/min caused weak but significant vasoconstriction (Pϭ0.0016 by ANOVA). Angiotensin-(1-7) at 100 pmol/min, but not at 10 pmol/min, significantly shifted the angiotensin II dose-response curve toward the right (meanϮSD of percent changes in forearm blood flow: Ϫ19Ϯ17%, Ϫ33Ϯ22%, Ϫ55Ϯ12%, Ϫ63Ϯ10%, and Ϫ68Ϯ5% at 5, 10, 25, 50, and 100 pmol/min of angiotensin II, respectively, with saline; 5Ϯ13%, 0.9Ϯ18%, Ϫ40Ϯ16%, Ϫ54Ϯ9%, and Ϫ61Ϯ6% with angiotensin-(1-7), Pϭ0.0021 by ANOVA). Angiotensin-(1-7) did not affect the dose-response curve of noradrenaline [3Ϯ12%, 5Ϯ16%, Ϫ20Ϯ22%, Ϫ31Ϯ18%, and Ϫ40Ϯ12% at 25, 50, 100, 300, and 600 pmol/min of noradrenaline, respectively, with saline; Ϫ4Ϯ15%, Ϫ2Ϯ23%, Ϫ29Ϯ22%, Ϫ34Ϯ16%, and Ϫ42Ϯ9% with angiotensin-(

The angiotensinogen (AGT) gene M235T variant is associated with essential hypertension and elevated plasma AGT concentrations, although the underlying mechanisms are unknown. Recent studies have suggested that AGCE 1 (human AGT gene core promoter element 1) located in the 5' upstream core promoter region (position -25 to -1) of the human AGT gene has an important part in the expression of AGT mRNA by binding with transcription factor AGCF 1 (human AGT gene core promoter element binding factor 1), and a mutation at -20 from adenine to cytosine (A-20C) increases the level of expression of this transcript. We therefore examined subjects with this mutation to study the association with increased plasma AGT concentrations and with essential hypertension. One hundred eighty-eight subjects receiving no antihypertensive medication were examined with regard to the correlation between A-20C and plasma AGT concentrations, and 234 subjects were studied with respect to the association between A-20C and essential hypertension. A-20C was determined by polymerase chain reaction-restriction fragment length polymorphism analysis with EcoOR 109I. Multiple regression analysis showed a weak but significant correlation between A-20C and plasma AGT concentrations (P=.047) and essential hypertension (P=.049). The results suggest that A-20C may underlie the increase in plasma AGT concentrations and be involved in the development of essential hypertension.

Detectable levels of G-CSF by enzyme-linked immunosorbent assay (ELISA) were found in sera of 4 out of 15 patients with head and neck carcinomas. Also cells prepared from the tumors of these 4 patients secreted G-CSF. The supernatants of cells derived from all 15 patients did not contain granulocyte-monocyte CSF, monocyte CSF, tumor necrosis factor-alpha, transforming growth factor-beta 1, epidermal growth factor, interleukin (IL)-1 beta and IL-6. These findings suggest that leukocytosis in patients with carcinomas might be due to the production of G-CSF by tumor cells.

Follow-up angiography was performed in 37 patients with right gastroepiploic artery (GEA) grafts at 27 +/- 32 days postoperatively. By the femoral approach, a 5F cobra or twist catheter was advanced selectively into the gastroduodenal artery (GDA) over a plastic-coated guidewire. In 29 patients, the GDA was successfully catheterized, and the GEA grafts were clearly visualized by the injection of 3-7 ml of contrast medium. GDA catheterization was unsuccessful in 8 patients, but in 4 of them the grafts were well visualized when 15-20 ml of contrast was injected. In the other 4 patients, visualization of the GEA grafts was poor, but the distal portions were outlined by retrograde perfusion from the native right coronary arteries. A total of 34 GEA grafts were patent (92%), and the diameters of these grafts were adequate when compared with respective recipient coronary arteries (2.8 +/- 0.9 and 2.3 +/- 0.6 mm, respectively; P less than .05). No complications were noted except for transient vasospasm (3 patients) in the GEA, hepatic artery, or both, which was relieved by the intra-arterial injection of isosorbide dinitrate (2.5 mg). Thus, the over-the-wire technique allows simple and safe GDA catheterization, which is essential for obtaining good visualization of GEA grafts.

The therapeutic effects of intravenous recombinant human erythropoietin (r-hEPO) administration on anemia induced by radiation therapy (3 cases), chemotherapy (18 cases) and combined therapies (5 cases) in patients with head and neck malignancies were examined. The effectiveness was evaluated by the changes in the hemoglobin concentration examined before and after the r-hEPO administration. The r-hEPO administration combined with anticancer therapies improved anemia induced by all three treatments. The therapeutic effectiveness of r-hEPO injection was also noted on anemia induced by all of four different chemotherapeutic regimens that have been ordinarily used for head and neck malignancies. Furthermore, the efficacy of the different dose schedules, 3000 IU (12 cases) or 6000 IU (14 cases), three times a week, was compared. Both of the r-hEPO dose schedules were effective for anemia, but the efficacy of 6000 IU was superior to that of 3000 IU. No significant changes were observed in the number of white blood cells and platelets and the results of biochemical examinations after the r-hEPO injection. There were no objective side-effects related to the r-hEPO administration. These results suggest that anemia induced by chemotherapy and/or radiotherapy could be prevented by r-hEPO administration. The addition of r-hEPO to anticancer therapies would make it possible to pursue the planned therapeutic schedules, prevent the decrease of immunity after allogeneic blood transfusion and bring about an-improvement in the prognosis of patients with malignancies.