OBJECTIVETo determine whether autoantibodies against the cardiac G-protein-coupled beta 2- and alpha 1-adrenergic and AT1 receptors are related to patients with primary hypertension.

METHODSSynthetic peptides corresponding to amino acid sequences of the second extracellular loops of the beta 2- and alpha 1-adrenergic and AT1 receptors were respectively used as antigens to screen sera from patients with hypertensive heart diseases (n = 50) as well as simple hypertension (n = 40) and healthy blood donors (n = 40) using ELISA test.

RESULTSThe positive ratio of autoantibodies against beta 2 and alpha 1 and AT1 receptors in patients with hypertensive heart diseases were significantly higher than patients with simple hypertension and healthy donors. The geometric mean titers of autoantibodies against beta 2- and alpha 1-adrenergic and AT1 receptors had no difference between the patients with hypertensive heart diseases and the patients with simple hypertension, but the geometric mean titers of two groups were higher than healthy donors. In the patients with hypertensive heart diseases, 81.0% of the patients with autoantibodies against beta 2-adrenergic receptor had autoantibodies against alpha 1-adrenergic receptor and 76.2% had autoantibodies against AT1 receptors. The percent of the autoantibodies against three receptors in patients with hypertensive heart diseases were 52.4%.

CONCLUSIONSAutoantibodies against beta 2- and alpha 1-adrenergic and AT1 receptors play an important role in the pathophysiological changes of primary hypertension, and may participate myocardial and vessel remodeling.

Adult ; Aged ; Autoantibodies ; blood ; Female ; Humans ; Hypertension ; immunology ; Male ; Middle Aged ; Receptor, Angiotensin, Type 1 ; immunology ; Receptors, Adrenergic, alpha-1 ; immunology ; Receptors, Adrenergic, beta-2 ; immunology

BACKGROUNDMany studies have suggested that angiotensin II (Ang II) and its receptors may be involved in the development of asthma. However, the expression of angiotensin II receptors (AGTR) is not clear in the lung tissue of chronic asthmatics. This study was designed to determine the relationship between airway remodeling, dysfunction and the expression of AGTRs in a rat model of asthma.

METHODSRats were sensitized with ovalbumin (OVA) for 2 weeks. Sixty minutes before an inhalation challenge, the rats were pretreated either with valsartan (15, 30, 50 mg x kg(-1) x d(-1)) or saline intragastrically. Then the rats received an OVA challenge for 30 alternative days. Acetylcholine (Ach)-induced bronchoconstriction was measured after the final antigen challenge. White cell counts in bronchoalveolar lavage fluid (BALF) and morphological changes in the airways were then assessed. The levels of transforming growth factor-beta 1 (TGF-beta(1)) and platelet-derived growth factor (PDGF) in BALF were detected by ELISA. The levels of AGTR1 and AGTR2 mRNA and protein in lung tissues were measured by RT-PCR and Western blotting.

RESULTSAGTR1 mRNA and protein levels in repeatedly OVA-challenged rats were significantly increased as compared with negative controls. The AGTR1 mRNA expression versus white cell counts of BALF and airway wall thickness (mainly in small airways) in lungs of chronic antigen-exposed rats were positively correlated. Valsartan decreased the level of AGTR1 in repeatedly OVA-challenged rats. However, AGTR2 mRNA and protein levels in the OVA-challenged rats and high-dose valsartan-treated rats (50 mg x kg(-1) x d(-1)) were also increased. Valsartan significantly decreased inflammatory cell accumulation and attenuated Ach-evoked bronchoconstriction in repeatedly antigen-challenged rats. Valsartan also decreased allergen-induced structural changes in rat airway (including total airway wall thickness and smooth muscle area) and the levels of TGF-beta(1) and PDGF in BALF.

CONCLUSIONSAGTR1 expression is potentially associated with airway remodeling and dysfunction in asthma. Ang II and AGTR1 may participate in airway inflammation and airway remodeling of chronic antigen-exposed rats. Valsartan, a AGTR1 antagonist, could inhibit AGTR1 expression and partially inhibits structural airway changes as well as airway inflammation in chronic OVA-exposed rats.

Angiotensin II Type 1 Receptor Blockers ; pharmacology ; Angiotensin Receptor Antagonists ; Animals ; Asthma ; chemically induced ; genetics ; metabolism ; Blotting, Western ; Bronchoalveolar Lavage Fluid ; chemistry ; Enzyme-Linked Immunosorbent Assay ; Gene Expression ; drug effects ; Lung ; drug effects ; metabolism ; pathology ; Male ; Ovalbumin ; Platelet-Derived Growth Factor ; metabolism ; Rats ; Rats, Wistar ; Receptor, Angiotensin, Type 1 ; genetics ; metabolism ; Receptor, Angiotensin, Type 2 ; genetics ; metabolism ; Receptors, Angiotensin ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Tetrazoles ; pharmacology ; Transforming Growth Factor beta1 ; metabolism ; Valine ; analogs & derivatives ; pharmacology ; Valsartan

OBJECTIVETo observe the positive rates of autoantibodies against beta1 adrenergic receptors (beta1-receptor) and angiotensin II type 1 receptors (AT(1)-receptor) in type 2 diabetes patients with or without hypertension.

METHODSThe epitopes of the second extracellular loop of beta1-receptor (197 - 222) and AT(1) receptor (165 - 191) were synthesized and serum autoantibodies were determined in type 2 diabetes patients with hypertension (n = 171) or without hypertension (n = 106). Left ventricular dimension was determined by echocardiography. The 24-hour urinary protein was measured by ELISA. The risk factors for enlarged left ventricle were analyzed by multiple logistic regressions.

RESULTSThe positive rates of the autoantibodies against beta1-receptors (45.0%) and AT(1)-receptor (46.2%) in patients with type 2 diabetes with hypertension were significantly higher than those in patients with type 2 diabetes without hypertension (16.0% and 10.4%, respectively, all P < 0.01). In type 2 diabetes patients with hypertension and enlarged left ventricle, the positive rates of the autoantibodies against beta1-receptor 61.4% (35/57) and against AT(1)-receptor 64.9% (37/57)were significantly higher than those in type 2 diabetes patients with normal left ventricular dimension (36.8%, 42/114 and 36.8%, 42/114, respectively, all P < 0.01). Regression analysis demonstrated that course of disease, systolic pressure, serum autoantibodies against beta1 adrenergic receptor and angiotensin II type 1 receptors sera autoantibodies were independent risk factors for left ventricular enlargement (all P < 0.05).

CONCLUSIONThe serum beta1 and AT(1)-receptor autoantibodies are related to enlarged left ventricle in type 2 diabetes patients with hypertension and suggest that autoantibodies against beta1 and AT(1)-receptor might play important roles in the pathogenesis of type 2 diabetes patients with hypertension and enlarged left ventricle.

Aged ; Autoantibodies ; blood ; Diabetes Mellitus, Type 2 ; complications ; immunology ; Female ; Humans ; Hypertrophy, Left Ventricular ; complications ; immunology ; Male ; Middle Aged ; Receptor, Angiotensin, Type 1 ; immunology ; Receptors, Adrenergic, beta-1 ; immunology

There are several widely used combinations of angiotensin II receptor blocker (ARB)/thiazide. The complimentary mechanism of action for such anti-hypertensive therapies is that, while ARB inhibits the vasoconstricting and aldosterone-secreting effects of angiotensin II, hydrochlorothiazide affects the renal tubular mechanisms of electrolyte reabsorption and increases excretion of sodium and chloride in the distal tubule, consequently promoting water excretion. In addition, hypokalemia, which may be triggered by a hydrochlorothiazide-induced increase in urinary potassium loss, is resisted by the use of ARB. Hence, the ARB/thiazide combination is safe in terms of potassium imbalance. For these reasons, fixed-dose ARB/thiazide combination anti-hypertensive drugs have been widely used for the treatment of hypertension. However, there have not been many studies done regarding cases where patients under such regimens showed severe hyponatremia, even when the amount of thiazide included was low. Here we report two cases in which severe hyponatremia occurred following treatment with the ARB/thiazide combinations. Upon discontinuation of the regimen, both patients showed recovery from hyponatremia.
Angiotensin II Type 1 Receptor Blockers ; Angiotensin II* ; Angiotensins* ; Antihypertensive Agents ; Humans ; Hydrochlorothiazide ; Hypertension ; Hypokalemia ; Hyponatremia* ; Potassium ; Receptors, Angiotensin* ; Sodium ; Water

No abstract available.
Angiotensin II ; Angiotensins ; Lithium ; Receptors, Angiotensin

No abstract available.
Angiotensin II ; Angiotensin Receptor Antagonists ; Angiotensins ; Hyperkalemia ; Receptors, Angiotensin

OBJECTIVETo identify the A1166/C polymorphism of angiotensin II type 1 receptor (AT1R) gene in patients with essential hypertension complicated with brain infarction (BI).

METHODSAT1R genotyping with polymerase chain reaction-restrictive fragment length polymorphism was performed in 70 normotensive subjects, 72 hypertensive patients without cardio-cerebrovascular diseases(EH-NCCVD) and 70 hypertensive patients with BI. The relationship between the polymorphism of AT1R gene and plasma lipid levels was also studied.

RESULTSThe frequencies of C allele in the two groups of hypertension were higher than that in the health controls, respectively (P<0.05). But there was no significant difference in the frequency of C allele between the two groups of hypertension. A positive correlation was observed between the lipoprotein(a) and AT1R gene A1166/C polymorphism in hypertensive patients.

CONCLUSIONAT1R gene contributes to the development of essential hypertensive, but not to the incidence of BI in the hypertensive.

Aged ; Alleles ; Brain Infarction ; complications ; Female ; Gene Frequency ; Humans ; Hypertension ; blood ; complications ; genetics ; Lipids ; blood ; Male ; Middle Aged ; Polymorphism, Genetic ; Receptor, Angiotensin, Type 1 ; Receptors, Angiotensin ; genetics

PURPOSE: It remains controversial how to treat the IgA nephropathy (IgAN) patients with proteinuria <1g/day. We investigated effects of single or combined use of angiotensin II receptor blocker (ARB) and steroid on proteinuria reduction and renal protection in IgAN patients with normal renal function and urine protein/creatinine ratio (PCR) < or =1 g/g. METHODS: Oral prednisolone was given at an initial dose of 1 mg/kg every day for 2 months and then gradually tapered for 4 months. An ARB irbesartan or losartan or valsartan was given until the end of follow-up. RESULTS: Over a mean follow-up period of about 40 mo, the urine PCR decreased from 0.64+/-0.29 g/g to 0.32+/-0.31 g/g in the combination group (n=26) (p<0.05). But in ARB (n=17) and steroid groups (n=20), it decreased from 0.56+/-0.26 g/g to 0.54+/-0.45 g/g and from 0.50+/-0.26 g/g to 0.34+/-0.32 g/g, respectively, while there were no statistical significances. Serum creatinine decreased from 0.83+/-0.13 mg/dL to 0.73+/-0.14 mg/dL in steroid group (p<0.01), and from 0.92+/-0.17 mg/dL to 0.81+/-0.23 mg/dL in combination group (p<0.01). But in ARB group, no statistical significance was noticed. All patients achieved the BP goal < or =130/80 mmHg by adding anti-hypertensive drugs, if necessary. CONCLUSION: Our results indicate that (steroid or) combination therapy reduced proteinuria and improved renal function in the patients with proteinuria < or =1 g/g. Further prospective controlled studies are required to clarify the effect of steroid over the long term.
Angiotensin II ; Angiotensin II Type 1 Receptor Blockers ; Angiotensins ; Antihypertensive Agents ; Biphenyl Compounds ; Creatinine ; Follow-Up Studies ; Glomerulonephritis ; Glomerulonephritis, IGA ; Humans ; Immunoglobulin A ; Losartan ; Polymerase Chain Reaction ; Prednisolone ; Proteinuria ; Receptors, Angiotensin ; Retrospective Studies ; Tetrazoles ; Valine ; Valsartan

OBJECTIVETo investigate the mechanism of a novel angiotensin II type 1 receptor-associated protein (ATRAP) interfering with angiotensin II type 1 (AT1) receptor-mediated vascular smooth muscle cell (VSMC) growth and neointimal formation.

METHODSVSMCs isolated from thoracic aorta of adult Sprague-Dawley (SD) rats were used in this study. ATRAP cDNA was subcloned into pcDNA3 vector and then transfected into VSMCs. DNA synthesis and extracellular signal-regulated kinase (ERK) and phospho-ERK expressions in VSMCs were assayed by measurement of 3H thymidine incorporation and Western blotting, respectively. Morphological changes were observed in the balloon injured artery with or without transfection of ATRAP cDNA using 12-week-old male SD rats.

RESULTSATRAP overexpression in VSMCs inhibited angiotensin II (Ang II)-induced 3H thymidine incorporation 48 hours after Ang II stimulation (P < 0.05). In VSMC, Ang II stimulation increased the phosphorylation of ERK, which reached the peak around 60 minutes. The activation of phospho-ERK was significantly decreased by ATRAP (P < 0.05). Neointimal formation was markedly inhibited by ATRAP overexpression in injuried arteries.

CONCLUSIONSThe AT1 receptor-derived activation of ERK plays an essential role in Ang II-induced VSMC growth. The growth inhibitory effects of ATRAP might be due to interfering with AT1 receptor-mediated activation of ERK in VSMC growth and neointimal formation.

Angiotensin II ; pharmacology ; Animals ; Aorta, Thoracic ; cytology ; Cell Division ; Extracellular Signal-Regulated MAP Kinases ; metabolism ; Male ; Muscle, Smooth, Vascular ; cytology ; physiology ; Phosphorylation ; Rats ; Rats, Sprague-Dawley ; Receptor, Angiotensin, Type 1 ; physiology ; Receptors, Angiotensin ; genetics ; physiology ; Transfection ; Tunica Intima ; cytology

No abstract available.
Angiotensin I ; Angiotensin II* ; Angiotensins* ; Autoradiography ; Receptors, Angiotensin* ; Renin* ; Renin-Angiotensin System*