BACKGROUND: The present study was attempted to compare enalapril, an angiotensin-converting enzyme inhibitor with losartan an angiotensin II (Ang II) receptor blocker in the inhibitory effects on the secretion of catecholamines (CA) from the perfused model of the rat adrenal gland. METHODS: The adrenal gland was isolated and perfused with Krebs-bicarbonate. CA was measured directly by using the fluorospectrophotometer. RESULTS: Both enalapril and losartan during perfusion into an adrenal vein for 90 minutes inhibited the CA release evoked by acetylcholine (ACh), 1.1-dimethyl-4-phenyl piperazinium (DMPP, a selective Nn agonist), high K+ (a direct membrane-depolarizer), 3-(m-chloro-phenyl-carbamoyl-oxy-2-butynyl-trimethyl ammonium (McN-A-343, a selective M1 agonist), and Ang II in a time-dependent manner. Also, in the presence of enalapril or losartan, the CA release evoked by veratridine (an activator of voltage-dependent Na+ channels), 6-dimethyl-3-nitro-4-(2-trifluoromethyl-phenyl)-pyridine-5-carboxylate (BAY-K-8644, an L-type Ca2+ channel activator), and cyclopiazonic acid (a cytoplasmic Ca2+-ATPase inhibitor) were significantly reduced. Based on the same concentration of enalapril and losartan, for the CA release evoked by ACh, high K+, DMPP, McN-A-343, Ang II, veratridine, BAY-K-8644, and cyclopiazonic acid, the following rank order of inhibitory potency was obtained: losartan > enalapril. In the simultaneous presence of enalapril and losartan, ACh-evoked CA secretion was more strongly inhibited compared with that of enalapril- or losartan-treated alone. CONCLUSIONS: Collectively, these results demonstrate that both enalapril and losartan inhibit the CA secretion evoked by activation of both cholinergic and Ang II type-1 receptors stimulation in the perfused rat adrenal medulla. When these two drugs were used in combination, their effects were enhanced, which may also be of clinical benefit. Based on concentration used in this study, the inhibitory effect of losartan on the CA secretion seems to be more potent than that of enalapril.
(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride ; 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester ; Acetylcholine ; Adrenal Glands ; Adrenal Medulla ; Ammonium Compounds ; Angiotensin II ; Animals ; Catecholamines ; Cytoplasm ; Dimethylphenylpiperazinium Iodide ; Enalapril* ; Losartan* ; Perfusion ; Rats ; Veins ; Veratridine

BACKGROUND: Obstructive sleep apnea (OSA) has been shown to be an important risk factor for metabolic syndrome and cardiovascular disease. Endothelial dysfunction plays a pivotal role in the pathophysiology of these diseases. However, little is known about the relationship between sleep apnea and microvascular endothelial dysfunction, as assessed by digital reactive hyperemia. METHODS: The study population consisted of 80 patients (mean age, 48 +/- 12 years-old; 65 men; 59 hypertensive). We measured apnea-hypopnea index (AHI) and mild OSA was defined as 5 < AHI <15 and moderate to severe OSA as AHI > or = 15. Reactive hyperemia index (RHI) derived from peripheral arterial tonometry (PAT) as measurement of endothelium-mediated vasodilatation. RESULTS: There were 61 OSA patients in the study population (AHI, 21.5 +/- 16.7 vs. 2.7 +/- 1.6 in non-OSA; p < 0.001). There were no significant difference in RHI and peripheral augmentation index (pAIx) between OSA and non-OSA group (RHI, 2.04 +/- 0.48 vs. 2.06 +/- 0.42; p = 0.894; pAIx, 21.7% +/- 24.0% vs. 21.7% +/- 30.0%; p = 1.000, respectively). Also, there was no significant difference in RHI and pAIx between mild (n = 31) and moderate to severe (n = 30) OSA group (RHI, 2.10 +/- 0.47 vs. 1.98 +/- 0.49; p = 0.333; pAIx, 24.2% +/- 20.7% vs. 19.0% +/- 27.2%; p = 0.407, respectively), either. Overall, no significant correlation between AHI and RHI was observed (r = -0.023, p = 0.837). The other OSA severity indices such as oxygen desaturation index, mean and minimum oxygen saturation were not correlated with RHI or pAIx. In the subgroup analysis for the OSA group, we could not find any significant relationships between AHI and PAT parameters, either. CONCLUSIONS: OSA was not observed to be associated with reactive hyperemia measured by PAT.
Cardiovascular Diseases ; Humans ; Hyperemia* ; Male ; Manometry ; Oxygen ; Risk Factors ; Sleep Apnea Syndromes ; Sleep Apnea, Obstructive* ; Vasodilation

BACKGROUND: Elevation of blood pressure (BP) and the increasing incidence of hypertension have been known to be associated with time course, especially age. But there is still lack of evidence of BP change and the association with biochemical markers or markers for subclinical organ damage in Korean general population. Thus, the purpose of this study is to investigate BP change and the related factors in established Korean mid-aged rural cohort. METHODS: This study was performed by using data from ARIRANG cohort (Atherosclerosis Risk of a Rural Area Korean General Population) in Gangwon rural area. Data were collected from baseline survey (Nov 2005-Jan 2008) and follow-up survey (Apr 2008-Jan 2011). Among 5,515 participants, 1,863 were analyzed after excluding individuals with hypertension, diabetes mellitus, cerebral infarction, myocardial infarction, missing data for BP, and newly-developed hypertension. RESULTS: Mean age was 53.4 +/- 8.2 years and men were 718 (38.5%). Mean follow-up period was 2.4 +/- 0.9 years. Baseline systolic and diastolic BP were 123.6 +/- 15.7 mm Hg and 79.2 +/- 10.8 mm Hg. Systolic BP changes were -10.9 +/- 15.3 mm Hg and diastolic BP changes were -7.7 +/- 11.8 mm Hg. In logistic regression analysis, predictors for elevation of systolic BP on follow-up were start regular exercise (odds ratio [OR], 0.765; 95% confidence interval [CI], 0.604 to 0.968; p=0.0257) and fasting glucose (OR, 0.984; 95% CI, 0.972 to 0.996; p=0.0102) and homeostasis assessment-insulin resistance (OR, 0.82; 95% CI, 0.707 to 0.952; p = 0.0086). CONCLUSIONS: Follow-up systolic and diastolic BP were significantly decreased when compared to baseline BP in mid-aged Korean rural cohort population. Long-term follow-up is needed to discriminate the periodic change of BP and the associated factors.
Atherosclerosis* ; Biomarkers ; Blood Pressure* ; Cerebral Infarction ; Cohort Studies ; Surveys and Questionnaires ; Diabetes Mellitus ; Fasting ; Follow-Up Studies ; Gangwon-do ; Glucose ; Homeostasis ; Humans ; Hypertension ; Incidence ; Logistic Models ; Male ; Myocardial Infarction ; Rural Population*

BACKGROUND: To compare the parameters of local carotid stiffness with those of global arterial stiffness and to investigate the effects of angiotensin II receptor blocker (ARB) on the parameters of local carotid arterial stiffness as well as global arterial stiffness. METHODS: The correlations of the parameters between local carotid and global arterial stiffness were compared at baseline, and the changes of these parameters were evaluated after 6 months of valsartan therapy in 50 patients with newly diagnosed hypertension. Diameter change, strain, and 2-dimensional circumferential strain (2D CS) of the carotid artery measured by speckle tracking method were used as parameters of local arterial stiffness, and the parameters of pulse wave velocity (PWV) and pulse wave analysis (PWA) were used as standard parameters of global arterial stiffness. RESULTS: Carotid 2D CS, not conventional strain or diameter change, showed significant correlation with age (r = -0.592, p < 0.01), brachial-ankle PWV (r = -0.338, p < 0.05), and augmentation index (r = -0.298, p < 0.05). After 6 months of medical therapy, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were decreased significantly (SBP: 155.9 +/- 14.2 to 137.6 +/- 10.5 mm Hg, p < 0.01; DBP: 90.1 +/- 11.8 to 81.6 +/- 8.0 mm Hg, p < 0.01). The parameters of PWV and PWA were significantly improved, but the parameters of carotid arterial stiffness were not changed significantly. CONCLUSIONS: In hypertensives, carotid 2D CS showed better correlation with ageing and the parameters of global arterial stiffness than conventional strain or diameter change of the carotid artery. Global arterial stiffness was improved by 6 months of medical treatment with ARB, but the local carotid arterial stiffness was not changed.
Angiotensin Receptor Antagonists ; Blood Pressure ; Carotid Arteries ; Humans ; Hypertension* ; Pulse Wave Analysis ; Receptors, Angiotensin ; Vascular Stiffness* ; Valsartan

BACKGROUND: To analyze the patterns of medical care utilization and its related factors in hypertensive patients during 19 years (1990-2008), utilizing national patient survey in Korea. METHODS: Using seven surveyed data, age-standardized medical care utilization increasing ratios for the inpatients and outpatients compared to the year of 1990 were calculated, respectively. Changes of medical facilities (%) of patients used in 1990, 1999, and 2008 were compared. For the outpatients, median length of stay and discharge mortality rate per 1,000 persons were calculated. Multivariate logistic regression methods were used to identify related factors of the resident patients and the comparison characteristics between hypertensives and the others of all subjects. Sample weights were used. RESULTS: The medical care utilization of hypertensives were increased for both inpatients and outpatients. However, the ratios were dramatically diminished after the standardization. Age-standardized ratios were 3.6 in outpatients and 5.9 in inpatients compared to 1990. For the outpatients, mainly used medical facilities were changed from general hospital to convalescent hospital. Also, median length of stay and discharge mortality rate were increased up to 5 times and 4 times compared to 1990. The odds of being resident patients were related with discharge as death and using oriental medical center convalescent hospital in 2008. Hypertensive patients were older than the others. Confined to hypertensive patients, member of National Health Insurance was more tend to be outpatients but less inpatients. CONCLUSIONS: Aging population and long-term care Act were presumed as the main reason for the increasing of medical care utilization in 1990 to 2008.
Aging ; Health Care Surveys ; Hospitals, Convalescent ; Hospitals, General ; Humans ; Hypertension ; Inpatients ; Korea ; Length of Stay ; Logistic Models ; Long-Term Care ; Mortality ; National Health Programs ; Outpatients ; Utilization Review ; Weights and Measures

BACKGROUND: Previous studies have reported that obesity increases heart rate variability. Body mass index (BMI) has been reported to affect blood pressure variability (BPV) over 24 hours. However, the diurnal variation in the effect of BMI on BPV has not been evaluated. This study aimed to clarify the diurnal variation in the effect of BMI on BPV. METHODS: A total of 2,044 patients were consecutively enrolled in this study, and the data were analyzed retrospectively. All patients underwent 24-hour ambulatory blood pressure monitoring. We divided patients into two groups according to BMI (non-obese group: n = 1,145, BMI < 25; obese group: n = 899, BMI > or = 25). We compared BPV during daytime and nighttime between the non-obese and obese groups. We also evaluated the impact of BMI on BPV by multivariate regression analysis. RESULTS: On univariate regression analysis, there was no significant difference in BPV during daytime (systolic BP [SBP] variability: 20.7 vs. 21.7, p = 0.511; diastolic BP [DBP] variability: 16.8 vs. 17.5, p = 0.539). However, both SBP variability (13.8 vs. 17.6, p = 0.009) and DBP variability (11.7 vs. 14.3, p = 0.042) during nighttime were affected significantly by BMI. After adjusting other compounding variables (age > 60 years, current smoking habit, hypertension, diabetes mellitus, and use of calcium channel blockers and renin-angiotensin-aldosterone system blockers), multivariate analysis showed that BMI was an independent factor associated with increase in BPV during the night (SBP variability: p = 0.039; DBP variability: p = 0.034). CONCLUSIONS: Obesity increased BPV during nighttime.
Blood Pressure Monitoring, Ambulatory ; Blood Pressure* ; Body Mass Index ; Calcium Channel Blockers ; Diabetes Mellitus ; Heart Rate ; Humans ; Hypertension ; Multivariate Analysis ; Obesity* ; Renin-Angiotensin System ; Retrospective Studies ; Smoke ; Smoking

BACKGROUND: The present study was designed to evaluate the possible renoprotective effects of tamoxifen in deoxycorticosterone acetate (DOCA)-salt hypertensive (DSH) rats and its role in inflammation and fibrosis in the kidney. METHODS: Male Sprague-Dawley rats, weighing 180 to 200 g, were used. All rats underwent unilateral nephrectomy. One week later, one group of rats (n = 8) was implanted with DOCA strips (200 mg/kg) and another group of rats (n = 8) was implanted with DOCA strips with co-treated with tamoxifen (10 mg/kg) through gavage feeding. Rats that did not implanted DOCA strips served as controls (n = 6). Two weeks later, the systolic blood pressure (SBP) was measured by tail-cuff method. The protein expression of transforming growth factor-beta (TGF-beta), Smad, alpha-smooth muscle actin (alpha-SMA), E-cadherin, ED-1, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) was determined in the kidney by immunoblotting. The mRNA expression of tumor necrosis factor-alpha (TNF-alpha), monocyte chemotactic protein-1 (MCP-1), and vascular cell adhesion molecule-1 (VCAM-1) was determined by real-time polymerase chain reaction. RESULTS: In DSH rats, SBP was increased, which was not affected by tamoxifen treatment. Serum creatinine level was comparable in DSH rats compared with controls, which was not affected by tamoxifen treatment. In DSH rats, the protein expression of TGF-beta, Smad 2/3, Smad 4, alpha-SMA, ED-1, COX-2, iNOS was increased compared with controls, and these changes were attenuated by tamoxifen treatment except that of TGF-beta. The mRNA expression of TNF-alpha, MCP-1, and VCAM-1 was increased, and expression of MCP-1 and VCAM-1 was counteracted by tamoxifen treatment. CONCLUSIONS: Tamoxifen is effective in preventing the progression of nephropathy in DSH rats, the mechanism of which is associated with anti-inflammation and anti-fibrotic effects.
Actins ; Animals ; Blood Pressure ; Cadherins ; Chemokine CCL2 ; Creatinine ; Cyclooxygenase 2 ; Desoxycorticosterone Acetate ; Desoxycorticosterone* ; Fibrosis ; Humans ; Hypertension ; Immunoblotting ; Inflammation ; Kidney ; Male ; Methods ; Muscles ; Nephrectomy ; Nitric Oxide Synthase Type II ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction ; RNA, Messenger ; Tamoxifen* ; Transforming Growth Factor beta ; Tumor Necrosis Factor-alpha ; Vascular Cell Adhesion Molecule-1

BACKGROUND: Left ventricular hypertrophy (LVH) offers prognostic information beyond that provided by the evaluation of traditional cardiovascular risk factors. However, the validation of electrocardiogram (ECG) criteria for the diagnosis of LVH is limited in Korea general population. The purpose of this study is to investigate the diagnostic accuracy of ECG criteria for the detection of LVH in general population. METHODS: In the present study, we investigated a total of 1,946 adults from the community-based cohort. The left ventricular mass index (LVMI) was estimated with echocardiographic measurement and adjusted with body surface area. LVH was defined as a value greater than or equal to the sex-specific 90th percentile value of LVMI. ECG criteria for the diagnosis of LVH were Sokolow-Lyon criteria and Cornell criteria. RESULTS: The LVMI was significantly higher in male subjects (91.1 +/- 23.9 g/m2 vs. 83.9 +/- 21.7 g/m2, p < 0.001). The cutoff values were 120.8 g/m2 in male subjects and 112.2 g/m2 in female subjects. The sensitivity and specificity of Sokolow-Lyon criteria were 5.6% and 93.6% in male, 4.1% and 97.8% in female. Those of Cornell criteria were 2.8% and 98.7% in male, 14.3% and 95.8% in female. In male, the area under the receiver operating characteristic curves of Sokolow-Lyon voltage and Cornell voltage were 0.55 and 0.52. And those in female were 0.59 and 0.60. CONCLUSIONS: In our community-based sample, ECG criteria showed low sensitivity and high specificity. The performance of ECG criteria for detection of LVH was suboptimal, suggesting limited usefulness of ECG as mass screening tools.
Adult ; Body Surface Area ; Cohort Studies* ; Diagnosis ; Echocardiography ; Electrocardiography* ; Female ; Humans ; Hypertrophy, Left Ventricular* ; Korea ; Male ; Mass Screening ; Risk Factors ; ROC Curve ; Sensitivity and Specificity

BACKGROUND: Endothelial dysfunction has been documented in patients with type 2 diabetes especially when combined with hypertension. We prospectively investigated the effects of pioglitazone in improving endothelial function in hypertensive type 2 diabetic patients during the 6-month follow-up. METHODS: Hypertensive type 2 diabetic patients were randomly assigned to pioglitazone (n = 25) or placebo (n = 25). Primary endpoint was to compare changes in brachial artery flow-mediated dilation (baFMD) between the 2 groups during the 6-month follow-up. Secondary endpoints were to compare changes in the circulating levels of microRNA-17, -21, 92a, -126, and -145 which have been known as indicators of endothelial cell migration and atherosclerosis progression during the 6-month follow-up. Inflammatory markers such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), high-sensitive C-reactive protein, adiponectin, soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1) were compared during the follow-up. RESULTS: The prevalences of risk factors such as hyperlipidemia, smoking, stroke, and family history of coronary artery disease did not show significant differences between the 2 groups. Increases in baFMD (0.33 +/- 0.34 mm vs. 0.02 +/- 0.25 mm, p < 0.05, respectively) and in the level of circulating microRNA-21 (0.23 +/- 0.05 vs. -0.06 +/- 0.04, p < 0.05, respectively) were significantly greater in the pioglitazone group when compared to the placebo group during the 6-month follow-up. No significant differences in the prevalences of new onset heart failure, fracture, and bladder cancer were noted during the follow-up between the 2 groups. Decreases in the levels of inflammatory marker such as IL-6 (-2.54 +/- 2.32 pg/mL vs. -1.34 +/- 2.12 pg/mL, p < 0.05, respectively), TNF-alpha (-1.54 +/- 1.51 pg/mL vs. 0.14 +/- 1.12 pg/mL, p < 0.05, respectively), sICAM-1 (-39 +/- 52 ng/mL vs. 6 +/- 72 ng/mL, p < 0.05, respectively), and sVCAM-1 (-154 +/- 198 ng/mL vs. -11 +/- 356 ng/mL, p < 0.05, respectively) were significantly greater in the pioglitazone group compared to the placebo group during the follow-up. CONCLUSIONS: In hypertensive type 2 diabetic patients, pioglitazone may increase baFMD and circulatory microRNA-21 and decrease inflammatory cytokines including IL-6, TNF-alpha, sICAM-1, and sVCAM-1.
Adiponectin ; Atherosclerosis ; Brachial Artery* ; C-Reactive Protein ; Coronary Artery Disease ; Cytokines ; Diabetes Mellitus ; Endothelial Cells ; Follow-Up Studies ; Heart Failure ; Humans ; Hyperlipidemias ; Hypertension ; Intercellular Adhesion Molecule-1 ; Interleukin-6 ; MicroRNAs ; Prevalence ; Prospective Studies ; Risk Factors ; Smoke ; Smoking ; Stroke ; Tumor Necrosis Factor-alpha ; Urinary Bladder Neoplasms ; Vascular Cell Adhesion Molecule-1

Middle aortic syndrome (MAS) is very uncommon vascular pathology characterized by a long segmental narrowing or obstruction of the abdominal and/or distal thoracic aorta, commonly involving with the visceral and renal arteries. This syndrome may be presented with various physical signs of coarctation of the aorta, including resistant hypertension, renal insufficiency and/or mesenteric ischemia. Here, we report a case of a 64-year-old man with severe hypertension. He was diagnosed with MAS associated with stenosis of visceral and renal vessels by use of computed tomography and magnetic resonance angiography.
Aorta, Abdominal ; Aorta, Thoracic ; Aortic Coarctation ; Constriction, Pathologic ; Hypertension ; Hypertension, Renal ; Ischemia ; Magnetic Resonance Angiography ; Renal Artery