The new angiotensin II (Ang II) receptor subtype blocker (AT1 receptor blocker) has been clinically used as an antihypertensive agent. However the actions of AT1 receptor blocker on myocyte hypertrophy in neonatal spontaneous hypertensive rat (SHRIzm) and WKYIzm are not fully understood. The purposes of this study were to investigate the differences in Ang II-induced myocyte hypertrophy between SHR and WKY, and which action of AT1 or AT2 receptor blocker is related to it's induction.Cardiac myocytes were prepared from the heart of neonatal SHR and WKY, and cultured in serum-free medium for 10 days. From the 2nd day of culture, Ang II was added to the culture medium. AT1 (CV-11974) or AT2 (PD-123319) receptor blocker, L type calcium channel blocker (nisoldipine), calmoduline antagonist (W-7), and protein kinase C (PKC) inhibitor (staurosporine) were added to the culture medium containing Ang II (10-8M). To assess cellular growth, cells were monitored with a video camera, and the area of the myocyte was measured using the video-micrometer system (VM-30, Olympus Co., Ltd.). BrdU uptake to DNA and colorimetric assay (MTT) for mitochondria were analyzed by ELISA reader.The results were as follows: 1) The areas of myocyte under Ang II were greater in SHR (4172 μm2) than WKY (2270 μm2). 2) Both BrdU uptake and the activity of dehydrogenase (MTT assay) were increased in SHR compared to WKY. 3) Staurosporine, CV-11974 and nisoldipine significantly suppressed the Ang II-induced hypertrophy, whereas W-7 and PD-123319 failed to suppress it.In conclusion, the cellular signals of Ang II -induced hypertrophy were upregulated. Also DNA synthesis and the activity of the hypertrophied cells were augmented in SHR, compared to WKY. These signals are transduced into the cell chiefly through AT1 receptor. The effect of AT2 receptor does not neccessarily counteract cellular growth through the AT1 receptor. PKC-dependent, rather than calcium-dependent signals seem to be critical in Ang II-induced cellular growth in SHR.
We investigated the risk of upper gastrointestinal (UGI) bleeding and the protective effect of concomitant anti-secretory drugs during dual antiplatelet therapy administered following implantation of drug-eluting stents (DES) for coronary heart disease. Because proton pump inhibitors (PPIs) are reported to decrease the platelet inhibitory effects of clopidogrel, we also assessed cardiovascular outcomes in patients taking thienopyridine derivatives with or without anti-secretory drug.We retrospectively analyzed 243 patients, who underwent DES implantation between January 2006 and December 2007 and were receiving dual anti-platelet therapy post-surgery. The main outcome measurement was the presence of UGI bleeding. Cardiovascular outcomes were assessed by follow-up coronary angiography (CAG) findings. Data were collected from medical records.Eight cases of UGI bleeding were observed during the follow-up period, none of whom were taking anti-secretory drugs. Among the 243 cases, 108 cases were taking anti-secretory drugs: a PPI (67 cases), and an H2 receptor antagonist (41 cases). No UGI bleeding was observed among patients who were taking concomitant anti-secretory drugs. The 1- and 2-year cumulative incidences of UGI bleeding among patients who were not taking anti-secretory drugs were 4.5% and 9.2%, respectively. When CAG findings were compared between patients not taking any anti-secretory drug, taking PPI, or taking H2RA, significantly more stenotic lesions of the coronary artery were observed in the PPI-treatment group.Concomitant use of an anti-secretory agent was associated with a reduced risk of UGI bleeding. Use of PPI may be associated with an attenuation of the effect of dual antiplatelet therapy.
Arteriosclerosis of the small arteries is one of the main causes of microvascular angina, and although some reports have shown favorable prognoses, there is progressive reduction in left ventricular function. The present study evaluated the prognosis of microvascular angina in 86 Japanese patients (51 women, 35 men; average age, 59±9 years) who had ischemic ST segment depression, normal coronary angiograms and small artery sclerosis confirmed by endomyocardial biopsies. The mean follow-up period was 7.2±3.4 years. Questionnaires regarding their symptoms, cardiac medication, and new events were sent to all patients. Eighty-five patients (98.9%) were still alive at the end of the follow-up period. Chest pain remained in 35.3%; the degree of pain was unchanged in 18.8%, and had lessened in 11.8%. None of the patients died of cardiac events or suffered from a myocardial infarction. At the end of the follow-up period, calcium antagonist was used in 63.5% of patients. Seventeen patients (20.0%) were free of antianginal medication. The prognosis of microvascular angina diagnosed by strict criteria was favorable. (Circ J 2002; 66: 691 - 695)
Abstract The incidence of coronary ectasia (CE) and the relationship between CE and coronary spasm that was said not to be apt to occur in patients with CE were studied. The study consisted of 1,373 patients (including 1,008 patients with ischemic heart disease) who underwent cardiac catheterization. In 74 patients with CE, coronary spasm was tested in 33 patients subjected to acetylcholine (ACh) provocation and in 17 patients subjected to ergonovine (Ergo) provocation. CE was found in 74 patients (5.4%), and its incidence was significantly higher (6.7%) in patients with ischemic heart disease. In addition, ACh and Ergo provocation tests gave positive results in 12 (36%) and 4 patients (24%), respectively. Spasm was not provoked as frequently in the ectatic portion as elsewhere. In addition, spasm was often found at the borders of the ectatic portion in both provocation tests. The incidence of coronary ectasia was higher than that described in previous reports, and coronary spasm was more often observed at the borders between ectatic and normal portions than elsewhere.
