Angiotensin-(1-9) ameliorates pulmonary arterial hypertension via angiotensin type II receptor

Angiotensin-(1-9) [Ang-(1-9)], generated from Ang I by Ang II converting enzyme 2, has been reported to have protective effects on cardiac and vascular remodeling. However, there is no report about the effect of Ang-(1-9) on pulmonary hypertension. The aim of the present study is to investigate whether Ang-(1-9) improves pulmonary vascular remodeling in monocrotaline (MCT)-induced pulmonary hypertensive rats. Sprague-Dawley rats received Ang-(1-9) (576 µg/kg/day) or saline via osmotic mini-pumps for 3 weeks. Three days after implantation of osmotic mini-pumps, 50 mg/kg MCT or vehicle were subcutaneously injected. MCT caused increases in right ventricular weight and systolic pressure, which were reduced by co-administration of Ang-(1-9). Ang-(1-9) also attenuated endothelial damage and medial hypertrophy of pulmonary arterioles as well as pulmonary fibrosis induced by MCT. The protective effects of Ang-(1-9) against pulmonary hypertension were inhibited by Ang type 2 receptor (AT₂R) blocker, but not by Mas receptor blocker. Additionally, the levels of LDH and inflammatory cytokines, such as TNF-α, MCP-1, IL-1β, and IL-6, in plasma were lower in Ang-(1-9) co-treated MCT group than in vehicle-treated MCT group. Changes in expressions of apoptosis-related proteins such as Bax, Bcl-2, Caspase-3 and -9 in the lung tissue of MCT rats were attenuated by the treatment with Ang-(1-9). These results indicate that Ang-(1-9) improves MCT-induced pulmonary hypertension by decreasing apoptosis and inflammatory reaction via AT₂R.

Comparative effects of angiotensin II and angiotensin-(4-8) on blood pressure and ANP secretion in rats

Angiotensin II (Ang II) is metabolized from N-terminal by aminopeptidases and from C-terminal by Ang converting enzyme (ACE) to generate several truncated angiotensin peptides (Angs). The truncated Angs have different biological effects but it remains unknown whether Ang-(4-8) is an active peptide. The present study was to investigate the effects of Ang-(4-8) on hemodynamics and atrial natriuretic peptide (ANP) secretion using isolated beating rat atria. Atrial stretch caused increases in atrial contractility by 60% and in ANP secretion by 70%. Ang-(4-8) (0.01, 0.1, and 1 µM) suppressed high stretch-induced ANP secretion in a dose-dependent manner. Ang-(4-8) (0.1 µM)-induced suppression of ANP secretion was attenuated by the pretreatment with an antagonist of Ang type 1 receptor (AT₁R) but not by an antagonist of AT₂R or AT₄R. Ang-(4-8)-induced suppression of ANP secretion was attenuated by the pretreatment with inhibitor of phospholipase (PLC), inositol triphosphate (IP₃) receptor, or nonspecific protein kinase C (PKC). The potency of Ang-(4-8) to inhibit ANP secretion was similar to Ang II. However, Ang-(4-8) 10 µM caused an increased mean arterial pressure which was similar to that by 1 nM Ang II. Therefore, we suggest that Ang-(4-8) suppresses high stretch-induced ANP secretion through the AT₁R and PLC/IP₃/PKC pathway. Ang-(4-8) is a biologically active peptide which functions as an inhibition mechanism of ANP secretion and an increment of blood pressure.

The Comparison between ITST(TM) (Intertrochanteric/Subtrochanteric) & DHS (Dynamic Hip Screw) in Unstable Femur Intertrochanteric Fracture

PURPOSE: To evaluate between DHS and ITST nail (2nd generation) on the treatment of unstable femur intertrochanteric fracture in patients over 70 years old. MATERIALS AND METHODS: 61 cases of unstable intertrochanteric fracture (grouped 37 patients with DHS and 24 patients with ITST) who were taken the operation from Mar. 2003 to Sep. 2007 were analysed regarding to union time, sliding length of lag screws, operation time, blood loss, postoperative complications and functional recovery score by Skovron. RESULTS: The mean union time was 14.7 weeks in study group (ITST). The mean union time was 16.2 weeks in control group (DHS). The lag screw slidings were 7.2 mm in study group and 8.7 mm in control group. The operation times were 57.9 min in study group and 76.9 min in control group. The amount of blood loss were 67.7 ml in study group and 227.4 ml in control group. The complications were 4 cases in study group and 4 cases in control group. The Skovron recovery scores were 76.5% in study group and 73.7% in control group. CONCLUSION: From a practical point of short operation time, less amount of bleeding and less complication, author think that the ITST nail is useful implant for treatment of unstable femur intertrochanteric fracture in patient of old age.