BACKGROUND: Alterations of mechanical properties in the vasculature may contribute to complications of hypertension. Since angiotensin II plays a pivotal role in these vascular abnormalities, we tested the hypothesis that the AT1 angiotensin receptor antagonist irbesartan, in contrast to the beta-blocker atenolol, would correct artery stiffness in essential hypertensive patients. METHODS: Thirty untreated essential hypertensive patients (48 +/- 7 years, range 35-65; 72% male) were randomly assigned in a single-blind fashion to irbesartan or atenolol treatment for 6 months. Fifty one age/sex-matched normotensive subjects were also studied. Systemic arterial stiffness (augmentation index; AI) was measured by the pressure transfer function using radial pulse tonometry. RESULTS: Both treatments reduced blood pressure (BP) to a comparable degree (irbesartan: 160 +/- 19/105 +/- 13 to 133 +/- 16/92 +/- 10 mmHg, p<0.01; atenolol: 166 +/- 17/113 +/- 9 to 132 +/- 15/90 +/- 8 mmHg, p<0.01). Other hemodynamic parameters of peripheral and central arteries showed similar degree of reduction, except significant reduction of central pulse pressure with irbesartan treatment (42 +/- 20 to 29 +/- 8 mmHg, p=0.01 vs 41 +/- 14 to 34 +/- 12 mmHg of atenolol treatment). After 6-month treatment, systemic arterial stiffness (AI) was significantly reduced from 28 +/- 11 to 21 +/- 11% (p=0.01) after irbesartan but atenolol treatment showed no change (from 29 +/- 8 to 29 +/- 13%). Reversal of arterial stiffness correlated mostly with reduction of central pulse pressure (r=0.63, p<0.01). CONCLUSION: The AT1 angiotensin antagonist irbesartan corrected the altered arterial stiffness from patients with essential hypertension by reduction of central pulse pressure, whereas the beta-blocker atenolol had no effect.
Angiotensin II ; Angiotensins* ; Arteries ; Atenolol ; Blood Pressure ; Hemodynamics ; Humans ; Hypertension* ; Manometry ; Receptors, Angiotensin ; Vascular Stiffness*

Whether immunosuppressive therapy may have beneficial effects in the treatment of IgA nephropathy remains controversial. ACE inhibitor or angiotensin II receptor antagonist(AIIA) are suggested to reduce urinary protein excretion(Up) in patients with renal diseases. We therefore investigated the effects of the angiotensin II receptor antagonist losartan on the proteinuria and renal function in patients with IgA nephropathy. AIIA reduced blood pressure in patients with hypertension, but there were no significant differences statistically before and after therapy. AIIA reduced Up after 1-4 months(2.8+/-1.1 to 1.1+/-1.0g/24h, p=0.001) and 7-13 months(2.8+/-1.1 to 1.7+/-0.6g/24h, p=0.017). There were no significant changes of serum creatinine levels after AIIA treatment. Cough or angioedema were not observed during AIIA treatment. In conclusion, AIIA may be useful in the treatment of patients with IgA nephropathy and proteinuria.
Angioedema ; Angiotensin II* ; Angiotensin Receptor Antagonists* ; Angiotensins* ; Blood Pressure ; Cough ; Creatinine ; Glomerulonephritis, IGA ; Humans ; Hypertension ; Losartan ; Proteinuria ; Receptors, Angiotensin*

To investigate the mechanisms underlying the cholinergic agonist carbachol-induced cardiovascular responses, changes of renin-angiotensin system were examined in fetal hormonal systems. In the ovine fetal model under stressless condition, the cardiovascular function was recorded. Blood samples were collected before (during baseline period) and after the intravenous administration of carbachol. Simultaneously, the levels of angiotensin I (Ang I), angiotensin II (Ang II) and vasopressin in the fetal plasma were detected by immunoradiological method. Also, blood gas, plasma osmolality and electrolyte concentrations were analyzed in blood samples. Results showed that in chronically prepared ovine fetus, intravenous infusion of carbachol led to a significant decrease of heart rate (P < 0.05), and a transient decrease followed by an increase of blood pressure (P < 0.05) within 30 min. After the intravenous infusion of carbachol, blood concentrations of Ang I and Ang II in near-term ovine fetus were both significantly increased (P < 0.05); however, blood concentration of vasopressin, values of blood gas, electrolytes and plasma osmolality in near-term ovine fetus were not significantly changed (P > 0.05). Blood levels of Ang I and Ang II in the atropine (M receptor antagonist) + carbachol intravenous administration group was lower than those in the carbachol group without atropine administration (P < 0.05). In conclusion, this study indicates that the near-term changes of cardiovascular system induced by intravenous administration of carbachol in ovine fetus, such as blood pressure and heart rate, are associated with the changes of hormones of circulatory renin-angiotensin system.
Angiotensin I ; blood ; Angiotensin II ; blood ; Animals ; Blood Pressure ; Carbachol ; pharmacology ; Cholinergic Agonists ; pharmacology ; Fetus ; Heart Rate ; Renin-Angiotensin System ; Sheep ; Vasopressins ; blood

The kidneys play a fundamental role in the long-term control of arterial pressure by regulating sodium balance and extracellular fluid volume. The renin-angiotensin system (RAS) is at the center of the regulation of hypertension and progressive renal injury. It has gradually become clear that not only systemic RAS, but also intrarenal RAS has specific effects in the pathogenesis and progression of hypertension and renal damage. All of the RAS components are exhibited in the kidney and intrarenal angiotensin II (Ang II) is formed by multiple mechanisms. The demonstration of much enhanced levels of Ang II within specific renal compartments points out selective local regulation of Ang II in the kidney, showing that intrarenal Ang II levels are regulated in a way different from circulating Ang II. The importance of the RAS in involving proper nephrogenesis is also well known, and suppression of the RAS during fetal development may play a key role in mediating the structural and physiological changes observed in models of fetal programming of hypertension.
Angiotensin II ; Arterial Pressure ; Blood Pressure ; Extracellular Fluid ; Fetal Development ; Hypertension ; Kidney ; Negotiating ; Renin-Angiotensin System ; Sodium

PURPOSE: Effects of renin-angiotensin system blockade on tubulointerstitial lesions were examined in adriamycin-induced nephropathy. METHODS: Male Sprague-Dawley rats were used. The three experimental groups were intravenously injected with adriamycin (2 mg/kg). After 6 weeks, rats showing heavy proteinuria were orally treated with either cilazapril 1 mg/kg/day (ACEi group, n=7) or losartan 10 mg/kg/day (ARB group, n=7) during the period of additional 6 weeks. The other group was maintained without any drugs (ADR group, n=6). The control group was without adriamycin treatment and maintained during the 12 weeks (Control, n=5). RESULTS: Systolic blood pressure was increased following the adriamycin treatment, which was normalized by treatment with cilazapril or losartan. Accordingly, cilazapril and losartan normalized the 24-h urine protein/creatinine ratio, in association with morphologic improvement of tubulointerstitial lesions. The expression of laminin beta1 was not altered in any experimental groups. CONCLUSION: These results suggest that angiotensin II plays an important role in tubulointerstitial lesions in adriamycin-induced nephropathy.
Angiotensin II ; Animals ; Blood Pressure ; Cilazapril ; Doxorubicin ; Humans ; Laminin ; Losartan ; Male ; Proteinuria ; Rats ; Rats, Sprague-Dawley ; Renin-Angiotensin System*

BACKGROUND: This study was designed to examine whether iNOS pathway is pathologically altered in experimental diabetic nephropathy and whether therapy with ACE inhibitor (imidapril: I) or angiotensin II type 1 receptor (AT1) blocker (L-158, 809: L) ameliorates these changes. METHODS: Male SD rats were injected with diluent (control: C) or streptozotocin. Diabetic (D) rats were then randomized to receive vehicle, I (2 mg/ kg/d) or L (1 mg/kg/d) by gavage. At the end of the 12-week treatment, rats underwent either a 4 hour placebo or an intraperitoneal LPS (2 mg/kg) challenge. Inducible NOS mRNA and protein were measured by RT-PCR and Western blot in isolated glomeruli. RESULTS: Systolic blood pressure and urinary protein excretion increased significantly in D rats compared with C. The basal expression of iNOS mRNA was increased in D rats compared with that of C, whereas there was no significant difference in the level of protein. Upon LPS stimulation, the iNOS mRNA and protein expression was significantly elevated in D rats. In D rats, this up-regulation of LPS-stimulated iNOS expression was equally ameliorated by both I and L in mRNA and protein levels. CONCLUSION: LPS-stimulated glomerular iNOS expression was enhanced in diabetic nephropathy, and the activation of angiotensin II may play a role in this enhancement.
Angiotensin II* ; Angiotensins* ; Animals ; Blood Pressure ; Blotting, Western ; Diabetic Nephropathies ; Humans ; Male ; Nitric Oxide Synthase Type II* ; Rats* ; Receptor, Angiotensin, Type 1 ; RNA, Messenger ; Streptozocin ; Up-Regulation

OBJECTIVETo investigate the changes of angiotensin II (Ang II) and its receptors in male rats with diabetic erectile dysfunction (DED) so as to study its effects.

METHODSOut of 40 male SD rats, 30 were taken at random for diabetic models. After 8 weeks, the rats with erectile dysfunction were selected from these models. All the rats were divided into 3 groups: control ( n = 10), diabetes mellitus( DM, n = 9) and DED (n = 8). For each rat, the Ang II levels in the blood and homogenate prepared from part of the isolated penile tissues were determined respectively, and the Ang II receptors of the rest of the penile tissues were analyzed through immunohistochemical (IHC) assay.

RESULTSCompared with the control group, Ang II levels in the blood and penile tissues in the DM group, and that in the blood of the DED group were very high and the differences were statistically significant (P < 0.05). Ang II in the penile tissues of the DED increased sharply (P < 0.01). The receptors of Ang II changed contrariwise to the level of Ang ll.

CONCLUSIONAng II may play an important role in the pathogenesis of DED, and the Ang II antagonist or inhibitor of the angiotensin-converting enzyme (ACEI) may become a therapeutic method for DED in the future.

Angiotensin II ; blood ; metabolism ; Animals ; Diabetes Complications ; blood ; metabolism ; Erectile Dysfunction ; blood ; etiology ; metabolism ; Immunohistochemistry ; Male ; Penis ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptors, Angiotensin ; blood ; metabolism

OBJECTIVETo assess whether Angiotensin II (Ang II) and carbon tetrachloride (CCl(4)) used in combination could accelerate the process of fibrosis and whether Ang II play a role in exagerating hepatic fibrosis in rats.

METHODSAng II was injected into the abdominal cavity of Sprague-Dawley (SD) rats together with subcutaneous injection of CCl(4). Rats were killed after 14 and 28 d. Blood serum and liver specimen were collected. The extent of fibrosis in the stained liver tissue sections was determined with the KS 400 Image Analysis System.

RESULTSRats receiving Ang II and CCl(4) for 28 d showed extensive liver fibrosis. Along with the increase of hepatic fibrosis, the serum concentration of Ang II went up gradually.

CONCLUSIONSA combination of Ang II and CCl(4) would accelerate the process of hepatic fibrosis. Ang II probably took part in the occurrence of heparic fibrosis.

Alanine Transaminase ; blood ; Angiotensin II ; blood ; toxicity ; Animals ; Aspartate Aminotransferases ; blood ; Carbon Tetrachloride ; toxicity ; Liver Cirrhosis, Experimental ; chemically induced ; Male ; Rats ; Rats, Sprague-Dawley ; Renin-Angiotensin System ; physiology

BACKGROUND/AIMS: Fimasartan is an angiotensin type 1 receptor blocker (ARB) which has comparable efficacy and tolerability with other ARBs. The aim of this study was to evaluate 24-hour blood pressure (BP) lowering efficacy and the tolerability of the low dose fimasartan compared with valsartan in patients with mild to moderate hypertension. METHODS: This study was a phase II, prospective, multicenter, randomized, double-blind, parallel-grouped trial. A total of 75 hypertensive patients, whose mean ambulatory BP monitoring values were ≥ 135/85 mmHg, were randomized to either fimasartan 30 mg or valsartan 80 mg daily. The primary efficacy endpoint was the change in the mean 24-hour systolic BP (SBP) values from the baseline and at the week 8. Secondary endpoints included the change in the mean 24-hour diastolic BP values, the daytime and the nighttime mean BP values at week 8, the trough-to-peak (T/P) ratio and the smoothness index. RESULTS: At week 8, the mean 24-hour SBP values significantly decreased in both groups; –10.5 ± 11.9 mmHg (p < 0.0001) in the fimasartan group and –5.5 ± 11.6 mmHg (p = 0.0307) in the valsartan group. The difference between two groups was 4.3 ± 2.9 mmHg but there was no statistical significance (p = 0.1392). The global T/P ratio in the fimasartan 30 mg groups were 0.48 and 0.40 in the valsartan 80 mg group, respectively (p = 0.3411). The most frequent adverse events (AEs) were acute pharyngitis and there were no cases of severe AEs. CONCLUSIONS: In mild-to-moderate hypertensive patients, low dose (30 mg) fimasartan showed comparable 24-hour BP lowering efficacy compared with valsartan (80 mg). There was no difference in tolerability between two groups.
Angiotensin II Type 1 Receptor Blockers ; Blood Pressure Monitoring, Ambulatory ; Blood Pressure* ; Humans ; Hypertension* ; Pharyngitis ; Prospective Studies ; Receptor, Angiotensin, Type 1 ; Valsartan

OBJECTIVE: To determine the relation between plasma tissue factor (TF) and serum angiotensin II(AngII) and the effect of different dosages of fosinopril on chronic heart failure(CHF). METHODS: Thirty healthy controls and 35 CHF patients were recruited to observe AngII,TF, left ventricular ejection fractions(LVEF) and left ventricular end-systolic volume index (LVESVI) at baseline and 10 weeks after the treatment. The 35 patients were randomly assigned into 2 groups: A routine dosage fosinopril group received 10 mg once daily and a middle dosage group received 10 mg twice a day for 10 weeks. RESULTS: Compared with the healthy controls, AngII,TF,and LVESVI significantly increased (P<0.01) and LVEF significantly decreased (P<0.01) in CHF patients. The TF was positively correlated with AngII(r=0.2491, P<0.01) in the patients. After the 10-week treatment with different dosages of fosinopril, AngII,TF,and LVESVI obviously decreased(P<0.05 or P<0.01) and LVEF significantly increased in the 2 groups (P<0.05 or P<0.01). The middle dosage group changed more than the routine dosage group (P<0.01). CONCLUSION TF is positively correlated with AngII in CHF patients. Fosinopril can greatly improve cardiac function and antagonize prethrobotic state,and the therapeutic effect improves with the dosage increase.
Aged ; Angiotensin II ; blood ; Angiotensin-Converting Enzyme Inhibitors ; administration & dosage ; Chronic Disease ; Female ; Fosinopril ; administration & dosage ; Heart Failure ; blood ; drug therapy ; Humans ; Male ; Middle Aged ; Thromboplastin ; metabolism