Materials and methods. An ~1.75-kb promoter region of SERCA2 gene was cloned with the pGL3 luciferase vector. The direct effects of Ang II on SERCA2 gene expression in HL-1 atrial myocytes were examined by promoter activity assay, followed by Western blot analysis for protein levels and quantitative real-time reverse transcription polymerase chain reaction for mRNA amounts.

Results. Ang II did not increase the promoter activity of the 1,754-bp promoter-receptor construct of the SERCA2 gene. The levels of SERCA2 protein and mRNA were also unchanged at different time points after Ang II treatment.

Conclusions. Although Ang II had prominent effects on SERCA2 in ventricular myocytes, it did not alter SERCA2 gene expression and protein levels in atrial myocytes. We provide a model for further investigation of the regulation of SERCA2 gene expression in atrial myocytes.

Methods. Infusion of subpressor doses of aldosterone with subcutaneously implanted mini-osmotic pumps (0.05 mg/kg/day) to rats for 21 days induced the development of endothelial dysfunction. In order to evaluate endothelial function, isometric tension studies were performed in response to acetylcholine and sodium nitroprusside.Additionally, PAR (the end product of activated PARP) and PARP-1 expressions in the endothelium of thoracic aortas were evaluated by immunohistochemistry.

Results. There was a significant loss of endothelium-dependent vasodilatation in response to acetylcholine in aldosterone-infused rats. In animals treated with 1,5-isoquinolinediol, the effect of aldosterone on vascular responsiveness was less than the untreated groups. Immunohistochemical studies demonstrated that aldosterone administration increased PAR and PARP-1 expressions in the endothelium of thoracic aortas, whereas PARP inhibition decreased their expressions to control levels.

Conclusion. Our results indicate that PARP activation in the vascular system may be a contributory factor to the impaired endothelial function associated with aldosterone administration.

Materials and methods. Chronically prepared near-term ovine foetuses (control and experimental: n=5, each group) were used.After 4—5 days’ surgical recovery, conscious ewes and their foetuses were tested in vivo.

Results. In response to intravenous atropine, foetal systolic, diastolic, and mean arterial pressure, as well as heart rate, increased immediately. Inhibition of muscarinic systems in the circulation caused a reduction of plasma angiotensin II levels, while angiotensin I in the circulation remained unchanged in the foetus. In addition, foetal plasma aldosterone levels were significantly increased following blockade of the cholinergic receptor, while other hormones, including arginine vasopressin, adrenocorticotrophic hormone, and atrial natriuretic peptide, were not changed in foetal blood under the same condition.

Conclusions. The results suggest that foetal automatic systems, not those hormonal factors tested, play a major role in cholinergic mechanisms mediating cardiovascular control. Furthermore, the data provide new information on how muscarinic inhibition affects renin-angiotensin system and adrenal cortex functions. Key words: aldosterone, angiotensin-converting enzyme, autonomic regulation, foetus

Methods. After placebo run-in, 842 patients (mean sitting diastolic blood pressure (BP) 95—109 mmHg) were randomised to aliskiren 150 mg or ramipril 5 mg. Dose titration and hydrochlorothiazide addition were allowed after Week 6 and 12, respectively, for inadequate BP control. Patients completing active treatment were re-randomised to current regimen or placebo during a 4-week posttreatment phase.

Results. BP reductions were independent of baseline PRA at Week 12, were greater with aliskiren- than ramipril-based therapy at Week 26 (17.9/13.3 vs. 15.2/12.0 mmHg, p<0.05) and persisted for longer after stopping aliskiren. Aliskiren-based therapy reduced geometric mean PRA (–63%, p<0.05; n=103), while ramipril-based therapy increased PRA (+143%, p<0.05; n=100) at Week 26; PRC increased in both groups (aliskiren: +224% [n=33], ramipril: +145% [n=39], both p<0.05). Four weeks after stopping aliskiren-based therapy, PRA remained 52% below pre-treatment baseline; PRA returned to baseline 2 weeks after stopping ramipril-based therapy.

Conclusions. Aliskiren-based therapy produced sustained BP and PRA reductions over 26 weeks; ramipril-based therapy lowered BP and increased PRA. PRA reductions persisted 4 weeks after stopping aliskiren, suggesting an inhibitory effect beyond the elimination half-life of the drug.

Methods. The patients were treated for a 12-month period with a candesartan-based regimen (8/16 mg + hydrochlorothiazide12.5 mg + additional drugs to target blood pressure < 140/90 mmHg [< 130/80 in diabetics]). Cornell voltage index (CorV), Cornell product (CorP), Sokolow-Lyon voltage index (SokV), and Sokolow-Lyon product (SokP) were calculated. In total 276 patients were included, 51 with diabetes.

Results. At study end, blood pressure was reduced 19.0±9.2/7.3±3.4 mmHg in diabetic patients and 18.8±9.1/8.0±3.2 mmHg in non-diabetic subjects (both p<0.01 vs. baseline; p=0.85 between groups).At baseline, 37.5% of diabetic and 26.4% of non-diabetic patients fulfilled criteria of ECG-LVH by CorP (p=0.02), 25.7% and 23.2%, respectively, by SokP (p=0.18), 11.8% and 13.7% by CorV (p=0.16), and 14.3% and 11.6% by SokV (p=0.10).At study end, the prevalence of ECG-LVH was reduced to 25.1% (relative risk reduction [RRR] 33.3%, p=0.001) and 18.2% (RRR 29.2%, p=0.001) by CorP and SokP, in diabetic patients, respectively. In non-diabetic patients, only the CorP criterion showed a significant decrease (RRR 18.9%, p=0.01). No significant changes were observed by other criteria.The RRR of ECG-LVH with treatment was significantly higher in diabetics according to CorP and SokP criteria.

Conclusions. The prevalence of ECG-LVH detected by CorP was higher in diabetics. Diabetics achieved higher reductions in ECG-LVH prevalence than non-diabetics with a candesartan-based regimen.

Subjects and methods. The present study included a total number of 221 subjects (107 myocardial infarction patients and 114 age- and sex-matched controls). Demographic and clinical characteristics were collected. Lipid profiles were estimated. DNA was isolated and the angiotensin II type 1 receptor gene A/C polymorphism was determined by polymerase chain reaction.

Results. Comparison of the lipid profiles between patients and controls showed that patients had statistically highly significant values (p=0.0001).The CC genotype of the angiotensin II type 1 receptor was not associated with myocardial infarction patients when compared to controls. CC vs. AA was ² = 2.08, odds ratio 2.30, 95% confidence interval 0.72 — 7.23, and p value was 0.14.

Conclusion. The angiotensin II type 1 receptor CC genotype is not a risk factor for myocardial infarction in patients in a South Indian population.

Subjects and methods. In the present case-control study, genotyping of 187 unrelated patients with MDD (44.89±12.92 years) and 207 unrelated healthy controls (41.34±9.76 years) from the northeastern part of Thailand was performed using polymerase chain reaction-restriction fragment length polymorphism technique.

Results. Comparing the two groups, no significant difference was observed with regard to either genotype distributions or allele frequencies of the –93T/C SNP of ACE. For the –240A/T SNP, a significant difference in genotype distributions was found (²=6.65, df=2, p=0.036).The presence of the –240A allele of ACE was associated with a decreased risk for MDD compared with the –240T allele (²=4.24, df=1, p=0.040, odds ratio=0.702 [95% confidence interval=0.508—0.971]). Moreover, haplotype frequency analysis revealed that the –240T/—93T combination was significantly over-represented in patients with MDD in comparison with controls (13.6% and 6.8%, p=0.002 on ² test, empirical p=0.004).

Conclusions. In the present investigation, an association between the –240A allele and a reduced risk for MDD was observed, but the genotype distributions of controls were only just in marginal agreement with Hardy-Weinberg equilibrium.The T-T haplotype in the ACE gene was significantly associated with an increased risk for MDD.

Materials and methods. We compared in a prospective double blind trial, the effects of treatment with enalapril or nifedipine on muscle performance in hypertensive elderly subjects. Patients were followed for nine months, and at baseline, 4.5 months and the end of follow-up, quadriceps and hand grip muscle strength, walking capacity, timed up and go and the short physical performance test were measured. Results. During follow-up, more subjects on nifedipine than on enalapril discontinued the medication due to side-effects. No differences in the evolution of muscle strength, walking capacity or functional measures were observed. At nine months, plasma angiotensin-converting enzyme activity decreased by 6.0±2.5 U/L among patients on enalapril and increased by 8.5±4.2 U/L (p<0.001) among patients on nifedipine.

Conclusion. In this group of elderly subjects, enalapril was not superior to nifedipine with regard to the age-related decline of muscle performance.

Results. PWDs were significantly shortened at the first, third and sixth months (41.7±8.8 ms, 39.1±6.9 ms and 38.3±7.1 ms, respectively) compared with baseline and first-week measurements (54.3±9.2 ms and 49.0±9.1 ms, respectively, p<0.001). Baseline PWD was correlated with body mass index (r=0.32, p=0.026), while PWD at the sixth month of treatment was significantly correlated with left atrial volume index (r=0.30, p=0.042). Multiple linear regression analysis revealed that PWD at the sixth month was related to baseline PWD (p=0.001).

Conclusion. Perindopril treatment significantly reduced PWD in hypertensive patients.

Materials and methods. The efficacy of a polymer-free drug-eluting stent coated with 300 mcg valsartan was compared to a coating with a 2% rapamycin solution in small (≤ 2.5 mm) coronary vessels with and without oral valsartan on the basis of the YUKON Choice stent system (Translumina GmbH, Hechingen, Germany). Fifteen patients (eight males, mean age 64.4±7.7 years) were treated with YUKON Choice valsartan-eluting stents and 30 patients (24 males, mean age 65.7±8.4 years) received YUKON Choice rapamycin-eluting stents. Clopidogrel was given for six months in all patients.

Results. Within the first 30 days, no adverse events occurred in either group. Binary in-stent restenosis rate was 30.8% (four in 13 angiographic controls) in the valsartan-eluting stent group and 35.0% (eight in 20 angiographic controls) in the rapamycin-eluting YUKON Choice stent group. Mean late lumen loss was 0.78±0.53 mm and 0.79±0.58 mm, respectively. Target lesion and target vessel revascularisation rate was 26.6% and 25.0%, respectively. No restenoses in rapamycin-eluting YUKON Choice stents appeared in 12 patients with adjunct oral valsartan administration.

Conclusions. If polymer-free YUKON Choice stents are used in small vessels, valsartan-eluting stents show an identical efficacy as rapamycin-loaded stents. In patients with rapamycin-eluting YUKON Choice stents it seems that the efficacy can be increased by oral valsartan administration.

Subjects and methods. This study comprised 79 Egyptian myocardial infarction cases with a mean age of 54.4±9.9 years including 60 males and 19 females, plus 238 healthy unrelated individuals of nearly matched age and sex as a control group. For all subjects, DNA testing for the angiotensin-converting enzyme gene I/D polymorphism was done using PCR amplification for detection of both the D and I alleles followed by a second run PCR specific for the I allele for samples typed as DD in the first run.

Results. Cases had a higher frequency of DD (29.1%) and ID (62.0%) genotypes than II (8.9%) genotype, with a higher frequency of D allele than I allele (64.4% vs. 33.6%). Compared to controls, cases had a significantly higher frequency of ID genotype (62.0% vs. 47.5%, p<0.05).This was more apparent among cases in the low risk group (p=0.002) than in the high risk group (p=0.041).

Conclusion. The angiotensin-converting enzyme gene I/D polymorphism is probably a risk factor for ischaemic heart disease among Egyptian cases, particularly if integrated with other environmental and genetic risk factors.

Materials and methods. We performed a matched case-control study among antihypertensive drug users. Pharmacy records and questionnaires were used to ascertain incident diabetes (cases), antihypertensive drug use, and risk factors. Controls did not (yet) have diabetes.We genotyped ACE (G4656C, which is in complete linkage disequilibrium with the ACE insertion/deletion polymorphism), angiotensinogen (M235T), and angiotensin II type 1 receptor (A1166C).

Results. Among 495 cases of incident diabetes and 2,624 controls, homozygous 1166C carriers of angiotensin II type 1 receptor who used angiotensin II receptor blockers had an increased risk of diabetes compared to 1166A carriers (interaction odds ratio 5.3 [95% confidence interval: 1.8-16.1]). Homozygous ACE GG subjects who used ACE inhibitors ≥ 1 defined daily dose/day had a higher risk of diabetes compared to subjects with the ACE C allele (interaction odds ratio 2.3 [95% confidence interval: 1.2-4.5]).

Conclusions. Angiotensin II receptor blockers increase the occurrence of diabetes in homozygous 1166C carriers of angiotensin II type 1 receptor, but not in 1166A carriers. ACE inhibitors at doses ≥ 1 defined daily dose/day increase the risk of diabetes among homozygous ACE GG carriers, but not in 4656C carriers.

Conclusions. In Iranian patients with type 2 diabetes, the D allele is associated with progression, but not development, of albuminuria.

Materials and methods. We compared the distribution of ACE insertion/deletion genotype and allele frequencies in two groups: a longevity group (399 subjects) aged over 90 years and a control group (302 subjects) aged less than 60 years.

Results. No difference in genotype and allele frequencies of the ACE gene insertion/deletion polymorphism was observed between the longevity group and the control group.When adjusting for gender, the difference between the longevity group and the control group was also not significant regarding the frequencies of the genotypes (male, p=0.994 and female, p=0.797) as well as allele frequencies (male, p=0.969 and female, p=0.884).

Conclusions. No association of the ACE gene insertion/deletion polymorphism with longevity was observed in our Han Chinese population.

Conclusion.This study demonstrates that increases of urinary sodium and potassium excretion elicited by central administration of Ang II are mediated by NAD(P)H oxidase- dependent production of superoxide and protein kinase C activation in conscious hydrated rats.

Materials and methods. Female Wistar rats treated with enalapril maleate (60 mg.kg^-1.d ^-1, n=38), losartan (20 mg.kg^-1.d^-1, n=36) or high salt diet (1% NaCl, n=38) were trained by two protocols (T1: 60-min swimming session, 5 days per week for 10 weeks and T2: the same T1 protocol until the 8^th week, then 9^th week they trained twice a day and 10^th week they trained three times a day). Salt loading prevented activation of the systemic RAS. Haemodynamic parameters, soleus citrate synthase (SCS) activity and LVH (left ventricular/body weight ratio, mg/g) were evaluated.

Results. Resting heart rate decreased in all trained groups. SCS activity increased 41% and 106% in T1 andT2 groups, respectively. LVH was 20% and 30% in T1 andT2 groups, respectively. Enalapril prevented 39% of the LVH in T2 group (p<0.05). Losartan prevented 41% in T1 and 50% inT2 (p<0.05) of the LVH in trained groups. Plasma renin activity (PRA) was inhibited in all salt groups and it was increased in T2 group.

Conclusions.These data provide evidence that the physiological LVH induced by swimming training is regulated by local RAS independent from the systemic, because the hypertrophic response was maintained even when PRA was inhibited by chronic salt loading. However, other systems can contribute to this process.

Materials and methods. In this observational pilot study, superoxide dismutase and catalase activities were evaluated in leucocyte lysates in a group of 21 HT patients at baseline and after two months of treatment with eprosartan (600 mg/ day). For the control group, 25 normotensive volunteers were recruited with comparable characteristics to the patients.

Results. The results obtained indicate, paradoxically, that the untreated HT patients present greater anti-oxidant enzyme activity than the control group.

Conclusion. This result could be interpreted as a cell defence mechanism against the greater oxidative stress that exists in these patients.This hypothesis is consistent with the facts reported previously by our group in which a reduction in oxidative stress was found after two months of treatment with eprosartan. ¹ Upon reducing this stress, less anti-oxidative activity would be necessary, just as was observed in the present study after two months of treatment with eprosartan.

Materials and methods. The references were retrieved through MEDLINE, Wanfang and VIP Information.The analyses were performed by the software STATA 9.0.

Results. No significant publication bias was observed.The combined data showed no association of the frequencies of the A allele with essential hypertension odds ratio (OR)=1.09 95% confidence interval (CI)=0.98—1.20;p=0.11 in female patients. No associations were shown between the frequencies of the A allele with the genetic susceptibility to essential hypertension in male patients (OR=1.11 95% CI=0.95—1.29; p=0.19).

Conclusion. The meta-analysis suggests that ACE2 G8790A polymorphism may not be a genetic risk factor for essential hypertension in a Chinese Han population.

Methods. In this study, we analysed the genotypic and the allelic distributions of the ACE I/D polymorphism and conducted a case/control association study between healthy normoglycaemic controls and diabetic patients in the two studied groups.ACE gene polymorphism was analysed by polymerase chain reaction in 272 individuals consisting of 172 diabetic subjects and 100 controls.

Results.The genotype frequencies for DD, ID and II were 75.50%, 19.60% and 4.89% inArabs and 76.66%, 16.66% and 6.67% in Berbers, respectively, in the case group, and 42.85%, 35.71% and 21.43% inArabs and 57.50%, 22.50% and 20.00% in Berbers, respectively, in the control group.The DD frequency was significantly higher in the case group than in the control group (p<0.001), suggesting that the DD genotype is associated with an increased susceptibility to type 2 diabetes in our study populations.

Conclusions.The current investigation provides new evidence regarding the role of the ACE I/D polymorphism in the pathogenesis of type 2 diabetes in Jerbian populations. Furthermore, it underlines the importance of ethnicity, which should be considered in all studies aiming to test the genetic effects on the susceptibility to type 2 diabetes.

Methods. Genotyping was performed by PCR-RFLP (restriction fragment length polymorphism) or PCR (polymerase chain reaction) using genomic DNA extracted from buccal cells of subjects with (101 cases) or without (307 controls) breast cancer.

Results.The frequencies of genotypes for ACE were: DD, ID and II (in %: cases: 60; 20; 20; controls: 46; 37; 17; p=0.019, ²); and for AT₁receptor were:AA,AC and CC (in %: cases: 65; 30; 5; controls: 51; 44; 5; p=0.114, ²).The results suggested that the A1166C polymorphism was not associated with breast cancer risk. On the other hand, for the ACE (I/D), there seemed to be different risks for cancer between cases and controls.

Conclusions.The ID genotype was less frequently associated with the disease than were the DD or II; that is, women with the ID genotype were 3.1 times less likely to develop breast cancer than those with the other genotypes.The ID genotype might be protective against breast cancer and the ACE (I/D) polymorphism a possible target for developing genetic markers for breast cancer.

Methods. The immunohistochemical signals of theAT₁-A and AT₁-B receptors were counted by stereological methods.¹

Results. The number of AT₁-B receptors in the efferent arterioles (expressed in signals/µm ³; mean (CV): 0.32 (0.33)) was significantly higher (78%; p<0.05) as compared with the number in the afferent arterioles (0.18 (0.11)). No differences were found in the AT₁-A receptors. In a number ofAT ₁-A receptors, significant differences (p<0.01) were detected between the afferent arteriolar renin-positive SMCs (0.13 (0.36)) and the number in renin-negative SMCs (0.25 (0.34)).The AT₁-B receptors did not display any differences.

Conclusions. These results indicate that the AT₁ receptor sub-types are regulated independently in the SMCs of the normal kidney arterioles.

Materials and methods. In 194 hypertensives and 304 controls of Hellenic origin, the possible association between the (CA)_n repeat polymorphism of angiotensinogen (AGT), the 250 bp insertion/deletion (I/D) of angiotensin-converting enzyme (ACE), the tetranucleotide repeat polymorphism (TCTG)_n of renin, and the (CT)_n repeat polymorphism of the natriuretic peptide receptor A (NPRA) and hypertension was assessed.

Results. No association between AGT and NPRA polymorphisms and hypertension was observed. The presence of ID or DD genotype of ACE was associated with an increased risk for hypertension compared with the II genotype (OR: 1.782 [95% CI: 1.032—3.077]), whereas the LL genotype of the renin gene was associated with a decreased risk compared with the SS genotype (OR: 0.174 [95% CI: 0.044—0.689]). However, after adjustment for confounding factors only the latter association remained.

Conclusions. In the present study conducted in a homogeneous Hellenic population, no associations betweenAGT,ACE, and NPRA gene polymorphisms and hypertension were found. The presence of a significant negative association between the LL polymorphism of the renin gene and hypertension requires further confirmation.

Materials and methods. A total of 260 subjects consisting of 65 HTN, 60 T2DM, 65 T2DM with HTN and 70 controls were recruited. Genotyping was performed by polymerase chain reaction initially and mistyping of DD genotypes was performed with an insertion-specific primer.

Results. The frequency for II, ID and DD genotypes of the ACE gene was 36.92%, 52.31% and 10.77% in HTN, 40.00%, 41.67% and 18.33% inT2DM, 30.77%, 53.85% and 15.38% inT2DM with HTN and 57.14%, 40.00% and 2.86% in controls, respectively. The frequency for the D allele was 36.92% in HTN, 39.17% in T2DM and 42.31% in T2DM with HTN compared to 22.86% in controls.The genotype and allele frequency of the ACE gene polymorphism differed significantly in patients when compared to controls (p < 0.05).

Conclusion. The D allele of the ACE gene is associated with essential HTN and T2DM in Malaysian subjects.

Methods. Twenty-nine patients with ARVD and 24 controls were included.AllARVD patients had documented sustained ventricular tachycardia. Thirteen patients had syncopal episodes. Six patients were resuscitated from sudden cardiac death.ACE gene polymorphism was identified by polymerase chain reaction technique.

Results. There was no significant difference in DD genotype frequency between ARVD patients and controls (44.8% vs. 45.8%, p=0.94). However, DD genotype frequency was significantly higher in ARVD patients with syncopal episodes compared to those without syncope (69.2% vs. 25.0%, p=0.017, odds ratio:6.750,95% confidence interval: 1.318—34.565). DD genotype was detected in higher frequency also in patients with a family history of sudden cardiac death (66.7% vs. 39.1%,p=0.36).

Conclusion. High prevalence of DD genotype in ARVD patients with syncope suggests that ACE I/D polymorphism might be useful in identifying high-risk patients for syncope.

Methods. Circulating ACE and AP-P levels were measured by activity assay using selective fluorogenic peptide substrates in plasma samples from the Leeds Family Study. In addition, the effect of progesterone on the expression of AP-P and ACE was examined in cells.

Results. Women on the OCP had higher age-adjusted plasma AP-P (mean [95% confidence interval]) (0.27 [0.23-0.32] nmol/min/ml (n = 53)) compared with women not on the OCP (0.17 [0.16-0.19] nmol/min/ml (n = 133), p < 0.001) or males (0.19 [0.17-0.20] nmol/min/ml (n = 209), p<0.001).There were no differences in the age-adjusted plasma ACE levels among the three groups. In HepG2 cells, progesterone treatment increased the AP-P protein and mRNA expression, whereas no effect of progesterone treatment was observed for ACE.

Conclusion. Increased AP-P may result in increased breakdown of bradykinin.These data suggest that progesterone-induced increases in AP-P may contribute to the development of OCP-induced hypertension in susceptible Women.

Methods. Four groups of adult male C57BL/6J mice were studied: group 1, untreated controls (tap water for six weeks); group 2, treated orally with a nitric oxide synthase inhibitor, N-nitro-L-arginine methyl ester (L-NAME, 0.325 mg/ml for six weeks); group 3, treated orally with captopril (0.6875 mg/ml for six weeks); group 4, co-treated orally with L-NAME and captopril (same doses for six weeks).At the end of the study, kidneys were placed in fixative and processed to paraffin for immunohistochemical staining.

Results. GAS-6 and its receptors were not present in control and L-NAME-treated mice. Positive GAS-6 staining was detectable only in those mice receiving some form of chronic dosing with captopril, whether they were treated with captopril only or with captopril and L-NAME. Immunohistochemical detection across cases for MER and RSE was rare, whereas AXL-positive staining in the kidney mirrored GAS-6 staining/expression.The staining of GAS6 and AXL was predominantly localised to the renal tubular cells.

Conclusions. These findings suggest that GAS-6 may not be a final common pathway for nitric oxide synthase inhibition-induced renal disease. Renal tubular GAS-6 expression following captopril treatment was unexpected and could be beneficial in preventing tubular atrophy following the onset of persistent systemic hypertension.