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

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

BACKGROUND: The aim of this study was to examine whether PD 123319 (an angiotensin II type 2 [AT2] receptor antagonist) can influence the release of catecholamines (CA) from the perfused model of the rat adrenal medulla. METHODS: The adrenal gland was isolated by the modification of Wakade method, and perfused with normal Krebs-bicarbonate solution. The content of CA was measured using the fluorospectrophotometer. RESULTS: During perfusion of PD 123319 (range, 5 to 50 nM) into an adrenal vein for 90 minutes the CA secretory responses evoked by acetylcholine (ACh), high K+, 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP), and McN-A-343 was dose- and time-dependently inhibited. Furthermore, loading with PD 123319 for 90 minutes also markedly inhibited the CA secretory responses evoked by 4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoro-methyl-phenyl)-pyridine-5-carboxylate (Bay-K-8644), cyclopiazonic acid, veratridine, and angiotensin II (Ang II). PD 123319 did not affect basal CA output. Simultaneous perfusion of PD 123319 and CGP 42112 perfused into an adrenal vein for 90 minutes rather more potently inhibited the CA seretory responses evoked by Ach, high K+, DMPP, Bay-K-8644, veratridine, and Ang II compared to the inhibitory effect by PD123319-treated alone. CONCLUSIONS: Taken together, these results show that PD 123319 inhibits the CA secretion evoked by both cholinergic and Ang II receptor stimulation from the perfused rat adrenal medulla. This inhibitory effect of PD 123319 seems to be exerted by blocking the influx of both Na+ and Ca2+ through their voltage-dependent channels into the rat adrenomedullary chromaffin cells as well as by reducing the Ca2+ release from its cytoplasmic calcium store, which may be relevant to AT2 receptor blockade. Based on these present data, it is thought that PD 123319 has different activity from previously known AT2 antagonist activity in the perfused adrenal medulla, and that AT2 receptors may be involved in the rat adrenomedullary CA secretion.
(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 ; Angiotensin II ; Angiotensin II Type 2 Receptor Blockers ; Animals ; Calcium ; Catecholamines ; Chromaffin Cells ; Cytoplasm ; Dimethylphenylpiperazinium Iodide ; Imidazoles ; Indoles ; Oligopeptides ; Perfusion ; Pyridines ; Rats ; Veins ; Veratridine

Hypertension is closely related to salt and water retention. The kidney plays an important role in the blood pressure regulation primarily to modulating tubular sodium and water reabsorption. The regulation of the salt and water balance depends upon an array of solute and water channels in the renal tubules. An altered regulation of sodium and water channels in the kidney may be related to various pathological conditions associated with altered salt and water retention. This review will discuss renal handling of sodium and water, with particular emphasis on aquaporins and renal sodium transporters and channels.
Aquaporins ; Blood Pressure ; Handling (Psychology) ; Hypertension ; Kidney ; Membrane Transport Proteins ; Retention (Psychology) ; Sodium ; Water

Since the first descriptions of their active functions more than ten years ago, small non-coding RNA species termed microRNA (miRNA) have emerged as essential regulators in a broad range of adaptive and maladaptive cellular processes. With an exceptionally rapid pace of discovery in this field, the dysregulation of many individual miRNAs has been implicated in the development and progression of various cardiovascular diseases. MiRNA are also expected to play crucial regulatory roles in the progression of pulmonary vascular diseases such as pulmonary hypertension (PH), yet direct insights in this field are only just emerging. This review will provide an overview of pulmonary hypertension and its molecular mechanisms, tailored for both basic scientists studying pulmonary vascular biology and physicians who manage PH in their clinical practice. We will describe the pathobiology of pulmonary hypertension and mechanisms of action of miRNA relevant to this disease. Moreover, we will summarize the potential roles of miRNA as biomarkers and therapeutic targets as well as future strategies for defining the cooperative actions of these powerful effectors in pulmonary vascular disease.
Anoxia ; Biomarkers ; Biology ; Cardiovascular Diseases ; Hydrogen-Ion Concentration ; Hypertension, Pulmonary ; MicroRNAs ; RNA, Small Untranslated ; Vascular Diseases