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: 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

Renovascular hypertension caused by renal artery stenosis is an uncommon but curative cause of hypertension in children. We report a case of recurrent severe hypertension caused by renovascular hypertension. After recurrence of hypertension after redo percutaneous transluminal renal angioplasty, the blood pressure was finally controlled by renal autotransplantation. This case demonstrates the importance of considering renovascular hypertension as a cause of severe hypertension in children. Also, renal autotransplantation should be considered as a viable treatment option for treatment of renovascular hypertension that is recurrent after renal angioplasty.
Angioplasty ; Blood Pressure ; Child ; Humans ; Hypertension ; Hypertension, Renovascular* ; Recurrence ; Renal Artery ; Renal Artery Obstruction ; Transplantation*

BACKGROUND: The device-guided breathing (DGB) exercise is a non-pharmacological treatment of high blood pressure (BP). Changes in hemodynamic variables after DGB remain to be defined. This study evaluated the hemodynamic effects of DGB in hypertensive patients. METHODS: Fifty-nine hypertensive individuals (male, 56%; age, 44 +/- 10 years) with systolic BP (SBP) in the range of 140 to169 mm Hg and diastolic BP (DBP) < 105 mm Hg were divided into two group: control group (n = 17) vs. DGB group (n = 42) who slowed respiratory rate by using 15 minutes daily DBG (RESPeRATE) over 8 weeks. Heart rate, BP and hemodynamic parameters including cardiac index (CI), thoracic fluid content (TFC), systemic vascular resistance index (SVRI) and total arterial compliance index (TACI) were measured using the ICG Monitor (CardioDynamics) at baseline and study end. RESULTS: Baseline characteristics were not different between the two groups. Office BP (SBP/DBP) was reduced from baseline to end value by 13.2 +/- 11.1/6.9 +/- 7.5 mm Hg in DGB group and 2.2 +/- 6.9/0.5 +/- 6.6 mm Hg in control group (p = 0.001, p = 0.004, respectively). Heart rate, CI, stroke index, and TFC were not changed in both groups. However, the SVRI was lower and the TACI was higher in DGB group than control group (SVRI: 2,728 +/- 599 vs. 3,141 +/- 714 dyne sec m2/cm5, p = 0.002; TACI: 0.845 +/- 0.194 vs. 0.761 +/- 0.184 mm Hg/mL/m2, p = 0.041). CONCLUSIONS: Daily device-guided breathing exercise for 8 weeks lowers the BP mediated by reducing the systemic vascular resistance and increasing the total arterial compliance without changes in heart rate and CI.
Breathing Exercises ; Cardiography, Impedance ; Heart Rate ; Hemodynamics* ; Humans ; Hypertension ; Respiratory Rate ; Vascular Resistance

BACKGROUND: Exaggerated blood pressure (BP) response to exercise can be an independent risk factor for cardiovascular mortality and morbidity. The purpose of this study was to define the factor that effect on early systolic BP response to exercise. METHODS: We examined echocardiographic data, BP, heart rate from graded exercise test and brachial ankle pulse wave velocity (PWV) of 205 patients (137 men and 68 women; mean age 58 +/- 11 years; range, 19 to 83 years). Graded exercise test was conducted in BRUCE protocol. We define delta systolic blood pressure (SBP) as systolic BRUCE stage "n" BP minus baseline BP. RESULTS: Resting BP (127 +/- 16 mm Hg) was elevated to 171 +/- 26 mm Hg after peak graded exercise test. Resting heart rate (80 +/- 15 bpm) was increased to 146 +/- 27 bpm after peak graded exercise test. Stepwise regression test between baseline SBP, delta SBP, maximal SBP and left atrial volume index (LAVI) was done. Supine SBP, delta SBP, maximal SBP was not associated with LAVI (p > 0.5). But increased LAVI was significantly associated with delta SBP1 in woman (R2 = 0.192, p = 0.002). PWV was significantly associated with base line (R2 = 0.311, p < 0.01) and maximal SBP (R2 = 0.051, p < 0.01). However, PWV was not associated with delta SBP. CONCLUSIONS: LAVI and PWV were not associated with early SBP response to exercise. But in women, elevation of early SBP during exercise is associated with LAVI.
Blood Pressure* ; Exercise Test* ; Female ; Heart Rate* ; Heart ; Humans ; Male ; Pulse Wave Analysis* ; Risk Factors

BACKGROUND: Pulmonary artery hypertension is characterized by persistent increase of vascular resistance, and is associated with right ventricle failure. We investigated changes of plasma renin, serum aldosterone, angiotensin converting enzyme (ACE) concentrations, ACE gene expressions and protein contents after bosentan treatment. METHODS: Six-week-old male Sprague-Dawley rats were divided into three groups: control (C) group, monocrotaline (M) group, and bosentan (B) group. Groups M and B were subcutaneously administered with 60 mg/kg of monocrotaline. In group B, 20 mg/kg/day of bosentan was administered by gavage twice a day. The rats were sacrificed after 1, 5, 7, 14, and 28 days. Changes of ACE gene expressions were analyzed by reverse transcription-polymerase chain reaction. Also, plasma renin, serum aldosterone, and ACE levels were measured. RESULTS: Serum aldosterone levels were significantly increased in group M compared with group C and significantly decreased after bosentan treatment on day 28. Serum ACE concentrations were significantly decreased compared with group M after bosentan treatment on day 28. Gene expressions of ACE were significantly increased in group M compared with group C on day 5 and significantly decreased after bosentan treatment on day 7 and 14. ACE protein contents significantly increased in group M compared with group C in week 2 and 4. It significantly decreased after bosentan treatment in week 2. CONCLUSIONS: The renin-angiotensin system is associated with pulmonary artery hypertension. To investigate the effects of bosentan on the renin-angiotensin system in pulmonary artery hypertension, further studies on the effects of bosentan according to different doses are required in the future.
Aldosterone ; Angiotensins ; Animals ; Gene Expression ; Heart Ventricles ; Humans ; Hypertension ; Hypertension, Pulmonary ; Male ; Monocrotaline ; Peptidyl-Dipeptidase A ; Plasma ; Pulmonary Artery ; Rats ; Rats, Sprague-Dawley ; Renin ; Renin-Angiotensin System ; Sulfonamides ; Vascular Resistance

BACKGROUND: Angiotensin II (AngII) and abnormal oscillatory shear stress are highly associated with vascular inflammation including atherosclerosis. However, it is poorly understood how interactions between AngII and shear stress in human aortic endothelial cells (HAEC) are involved in mechanisms by which cellular adhesion molecules are expressed. The purpose of this study was to improve that understanding. METHODS: AngII (10(-7)M for 6 hr) and two-types of shear stress treatments were used: laminar shear stress (LS: unidirectional, 12 dynes/cm2) and oscillatory shear stress (OS: bi-directional, 5 dynes/cm2, 1 Hz) in HAEC. Immunoblotting was used to detect expression of cellular adhesion molecules markers such as vascular cell adhesion molecule 1 (VCAM1) and intercellular adhesion molecule 1 (ICAM1). RESULTS: AngII significantly increased VCAM1 and ICAM1 expression in HAEC that had been reduced due to pretreatment with telmisartan. AngII-LS co-stimulation and AngII-OS co-stimulation significantly increased VCAM1 and ICAM1 expression in HAEC. The expression levels of VCAM1 and ICAM1 were also, significantly reduced when pretreated with telmisartan. However, VCAM1 and ICAM1 expression were significantly reduced under LS and OS stimulation. CONCLUSIONS: Telmisartan may modulate the expressions of VCAM1 and ICAM1 via different types of shear stress in HAEC that are activated by AngII.
Angiotensin II ; Angiotensins ; Atherosclerosis ; Benzimidazoles ; Benzoates ; Endothelial Cells ; Humans ; Immunoblotting ; Inflammation ; Intercellular Adhesion Molecule-1 ; Vascular Cell Adhesion Molecule-1

Hypertension is an independent risk factor of atherosclerotic cardiovascular disease. Diabetes multiplies the risk when combined. Therefore, it is crucial for the doctors to control the blood pressure (BP) properly in hypertensive patients with diabetes. And then, how much do we lower the BP? Several guidelines recommend target BP levels to minimize the risk under the basis of so many experimental and observational studies. But, we must consider several factors to properly apply the guidelines in the clinical fields. First, diabetes is not a uniform but a diverse disease. From asymptomatic microvascular disease to macrovascular cardiovascular disease, diabetic clinical findings are so different. So we must define where the patients stand in long diabetic road, and what the patients want to us. Second, because more people are becoming health-conscious, more people take the aspirin, lipid-lowering agents and other medications. It's means that interpretation of the results of recent studies is more difficult than previous, old studies. Third, measuring the BP in the hospital is really reflect the ambulatory BP? Now, it's too early to conclude that the one is more better than the other. From the next study, we can consider the use of ambulatory, home BP monitoring combined with hospital BP measuring. Finally, although BP lowering-effects are similar, all anti-hypertensives do not have same effect in diabetic patients. For example, angiotensin converting enzyme-inhibitor is more superior than calcium channel blocker in patients with heart failure. So, we must consider what type of drug used in the study.
Angiotensins ; Antihypertensive Agents ; Aspirin ; Blood Pressure ; Calcium Channels ; Cardiovascular Diseases ; Heart Failure ; Humans ; Hypertension ; Risk Factors