Zbigniew Heleniak, Zbigniew Zdrojewski, Piotr Wisniewski, Leszek Bieniaszewski, Boleslaw Rutkowski and Alicja Debska-Slizien
Endothelial dysfunction could be related to the limited availability of nitric oxide (NO). NO is synthesized with the participation of an NO synthase whose activity is inhibited by asymmetric dimethylarginine (ADMA). The synthesis of ADMA is exacerbated by oxidative stress, and several studies have shown the efficacy of drugs acting on the renin-angiotensin-aldosterone system (RAAS) (converting enzyme inhibitors and angiotensin II receptor antagonists) in reducing the level of ADMA. The probable mechanism of drug action is a reduction of oxidative stress through a decrease of angiotensin II formation. The aim of this study was to assess the influence of RAAS blockers on the plasma concentration of ADMA in patients with chronic glomerulonephritis (ChGN). The study included 37 patients, placed into group A and group B, depending on the treatment. Both groups were treated with RAAS blockers. In group B, immunosuppressive drugs were additionally administered. The control visits were at the 0, 6 and 12 months of observation. In both the studied groups (A+B), a significant reduction of ADMA (0.77 vs 0.4 μmol/l; p<0.05) was noticed. In patients suffering from ChGN, the use of RAAS blockers resulted in a significant decrease of plasma ADMA concentration, independently of immunosupressive treatment.
Nebojsa Tasic, Danijela Tasic, Dalibor Dragisic and Miroslav Mitrovic
Plasma-renin values vary in normotensive and hypertensive populations. Some studies consider renin to be a key factor in the aetiology of hypertension, but other studies note that renin is an important factor in cardiovascular homeostasis and functions more as a growth factor than as a pressor hormone. The aim of this study was to assess the PRA and aldosterone values under different salt intake regimes in patients with essential hypertension. The study group consisted of 50 untreated patients (27 women and 23 men; average age 42±9,2 yrs.; average BMI 27,91±4,6 kg/m2) with essential hypertension. All patients were put on a high-sodium diet (200 mmol NaCl per day) for one week after a week on a low-sodium diet (20 mmol NaCl per day). Sodium sensitivity (SS) was defined as a 10-mmHg increase in the mean blood pressure at the end of the high- vs. the low-sodium diet. The SS group consisted of 26 patients, and the sodiuminsensitive group consisted of 24 patients. The PRA and aldosterone levels were determined in 12 patients. PRA values in the SS group during rest were significantly lower compared with the salt-resistant group during all regimes of salt intake (F=10,56, p=0,0012). Salt loading in SS patients causes a significant decrease in PRA (in rest and effort) values in comparison to values during a low salt intake regime (rest: t=4,49, p<0,001; effort: t=3,45, p<0,01). The PRA values in the salt-resistant group did not vary significantly under the different salt intake regimes. The aldosterone values followed the pattern of the PRA values. It is necessary to distinguish investigations on salt intake effects based on incidence and value of blood pressure and investigations on salt restriction’s effects on of blood pressure levels (i.e., non-pharmacological hypertension therapy).
Samia Abd El-Moneim Ebied, Nadia Aly Sadek, Nadia El-Sayed Zaki, Samir Ali Abd El- Kaream and Heba Khafagui Ahmed El Kashif
The renin-angiotensin system (RAS) is a bioenzymic cascade that plays an integral role in cardiovascular homoeostasis by influencing vascular tone, fluid and electrolyte balance and the sympathetic nervous system. RAS was viewed as a circulating endocrine system, whereby renin released from the juxtaglomerular cells of the kidney cleaves the liver-derived macroglobulin precursor angio-tensinogen, to produce the inactive decapeptide angiotensin I, which is then converted to the active octapeptide Ang II by angiotensin converting enzyme (ACE) within the pulmonary. There is increasing evidence that Ang II, a major regulator of blood pressure and cardiovascular homeostasis, is involved in the regulation of cell proliferation, angiogenesis, inflammation and tissue remodeling, which suggests that this peptide might also play a role in cancer. Ang II is the main effector of the RAS and it alternatively binds to either Ang II T1R or Ang II T2R. The Ang II T1R and Ang II T2R can act as antagonists, and mediate effects on cell migration and proliferation of metastatic cancer cells and hemopoietic stem-progenitor cells. Components of the RAS are frequently differentially expressed in various cancers in comparison with their corresponding non- malignant tissue. Yet, the RAS has not been fully elucidated in patients with acute leukemia. Objective: The aim of the present work was to study serum level of Angiotensin II receptor type 1 and the soluble angiotensin converting enzyme (CD143) in patients with acute leukemia in order to extrapolate their possible prognostic value.
Subjects and Methods
The present study included 20 healthy volunteers clinically free from hypertension or sarcoidosis, 20 patients of newly diagnosed AML and 20 patients of newly diagnosed ALL. Blood samples were collected from all subjects and the level of serum ACE and serum Ang IIT1R were measured by enzyme linked immunossorbent assay.
The activity of ACE (U/L) and the concentration of Ang IIT1R (U/L) in patients groups with either AML or ALL before therapy were significantly higher than in control group. After therapy, the activity of the enzyme and its receptor concentration in both groups of patients were significantly decreased but still significantly higher than in normal control subjects.
Estimating the serum level of ACE and soluble Ang IIT1R is of informative diagnostic and prognostic value. Estimation serum level of ACE and Ang IIT1R levels in patients with either AML or ALL is of value in deciding the treatment protocol.
I Prieto, AB Segarra, M Martinez-Canamero, M De Gasparo, S Zorad and M Ramirez-Sanchez
The cardiovascular control involves a bidirectional functional connection between the brain and heart. We hypothesize that this connection could be extended to other organs using endocrine and autonomic nervous systems (ANS) as communication pathways. This implies a neuroendocrine interaction controlling particularly the cardiovascular function where the enzymatic cascade of the renin-angiotensin system (RAS) plays an essential role. It acts not only through its classic endocrine connection but also the ANS. In addition, the brain is functionally, anatomically, and neurochemically asymmetric. Moreover, this asymmetry goes even beyond the brain and it includes both sides of the peripheral nervous and neuroendocrine systems. We revised the available information and analyze the asymmetrical neuroendocrine bidirectional interaction for the cardiovascular control. Negative and positive correlations involving the RAS have been observed between brain, heart, kidney, gut, and plasma in physiologic and pathologic conditions. The central role of the peptides and enzymes of the RAS within this neurovisceral communication, as well as the importance of the asymmetrical distribution of the various RAS components in the pathologies involving this connection, are particularly discussed. In conclusion, there are numerous evidences supporting the existence of a neurovisceral connection with multiorgan involvement that controls, among others, the cardiovascular function. This connection is asymmetrically organized.
Dejan Petrovic, Miodrag Sreckovic, Tomislav Nikolic, Marija Zivkovic-Radojevic and Vladimir Miloradovic
Renovascular hypertension is caused by renal artery stenosis. Its prevalence in populations of hypertensive patients is 1-8%, and in populations of patients with resistant hypertension, it is up to 20%. The two main causes of stenosis are atherosclerosis and fibromuscular dysplasia of the renal artery. The main clinical consequences of renal artery stenosis include renovascular hypertension, ischemic nephropathy and “flash” acute pulmonary oedema. Unilateral stenosis of the renal artery causes angiotensin II-dependent hypertension, and bilateral stenosis of the renal arteries produces volume-dependent hypertension. Renovascular aetiology of hypertension should be questioned in patients with resistant hypertension, hypertension with a murmur identified upon auscultation of the renal arteries, and a noticeable side-to-side difference in kidney size. Non-invasive diagnostic tests include the determination of concentrations of peripheral vein plasma renin activity, the captopril test, captopril scintigraphy, colour Doppler ultrasonography, computed tomography angiography, and nuclear resonance angiography. Renovasography represents the gold standard for the diagnosis of renovascular hypertension. The indications for revascularization of the renal artery include haemodynamically significant renal artery stenosis (with a systolic pressure gradient at the site of stenosis of - ΔP ≥ 20 mmHg, along with the ratio of the pressure in the distal part of the renal artery (Pd) and aortic pressure (Pa) less than 0.9 (Pd/Pa < 0.9)), resistant hypertension, loss of renal function after administration of ACE inhibitors or angiotensin receptor II blockers, and recurrent flash pulmonary oedema associated with bilateral renal artery stenosis. The contraindications for renal artery revascularization include a longitudinal diameter of the affected kidney that is less than 8.0 cm, the resistance index measured from the segmental arteries peak blood flow (RI) > 0.8, chronic kidney disease (GFR <30 ml/min/1.73 m2) and negative captopril scintigraphy (lack of lateralization).
Pană Camelia, Fâșie Dragoș, Voinea Claudia and Tuță Liliana Ana
Polycystic kidney disease is an autosomal dominant genetic disorder (ADPKD) associated with arterial hypertension, as a common and early manifestation. However, the combination of hypertension and hypokalemia is very rare in these patients and may have another cause. We present a case of a 45 years old man with ADPKD associated with primary hyperaldosteronism. Unilateral suprarenal macroadenoma on abdominal CT scan, severe hypokalemia and low activity of plasmatic renin led to diagnosis.
Dana Pop, Adela-Viviana Sitar-Tăut, Lucia Procopciuc, Mirela Cebanu, M. Zdrenghea and D. Zdrenghea
Background. Genetic polymorphism of renin-angiotensin-aldosterone system affects the pathogenesis of hypertension (HTN), ischemic heart disease (IHD) and heart failure (HF). The purpose of our study is to analyze A/G renin genetic polymorphism in heart failure patients.
Methods. We investigated renin polymorphism in 83 subjects hospitalized in the Cardiology Department of the Rehabilitation Hospital Cluj-Napoca, using the PCR amplification method. 43 patients were diagnosed with heart failure [NYHA III-IV class], and 40 subjects without cardiovascular disease (control group). The NT-proBNP and the presence of cardiovascular risk factors were assessed.
Results. Heart failure etiology was IHD in 60.46 % of patients. The average value of NT-pro BNP was 2991.24 ± 2034.6 pg/ml. As it was expected, HF patients presented low lipid levels: total cholesterol = 162.36 ± 38.28mg/dl, LDL-Cholesterol = 104.88 ± 27.60mg/dl, triglycerides= 109.12 ± 55.84mg/dl, HDL-Co= 35.68 ± 9.55mg/dl. A/G renin genetic polymorphism [with pathogenic potential] in heart failure patients was of 60.46% (homozygote 4.65% and heterozygote 55.81%). Conversely, pathogenic mutations were found only in 38.46% of hypertensive patients, but also in 55.88% and 22.22% patients with obesity/overweight and diabetes. The heterozygote form was found in only 37.5% of control subjects.
Conclusion. This study showed no involvement of A/G renin polymorphisms in the pathogenesis of HF.
Marko Ravic, Vladimir Jakovljevic, Petar Ristic, Ivan Srejovic, Aleksandra Vranic, Goran Babic and Sergey Bolevich
Diabetes mellitus is a major risk factor for cardiovascular diseases, while cardiovascular diseases are a leading cause of morbidity and mortality worldwide. The renin-angiotensin- aldosterone system controls renal, cardiovascular, adrenal function and regulates fluid and electrolyte balance as well as blood pressure. Because of his role, inhibition of reninangiotensin- aldosteron system is another therapy approach that reduces the risk of diabetes and cardiovascular disease. In this study, our goal was to evaluate effect of valsartan,as inhibitor of angiotensin II receptor type 1, on cardiac tissue and function, with focus on cardiodynamic and oxidative stress. The present study was carried out on 20 adult male Wistar albino rats (8 week old and with body masses of 180- 200 g). Rats were divided randomly into 2 groups (10 animals per group). Healthy animals treated with 1 μM of valsartan and streptozotocin-induced diabetic animals perfused with 1 μM of valsartan 4 weeks after the induction of diabetes. Our results demonstrated that acute application of valsartan has different effect on cardiodynamics in rat heart of diabetic and healthy animals but did not improve cardiac function in hyperglycemia- induced changes. A challenge for further investigations are studies with chronic or acute administration, alone or in combination with other angiotensin-converting-enzyme inhibitor in various models of diabetes.
Chronic kidney disease, no matter the aetiology, has a progressive evolution and a negative prognosis. The rapidity of nephrons loss and deterioration of renal function depends on the aetiology of the kidney disease, the prompt diagnosis, efficiency of the treatment and the patient compliance to the treatment, diet and suitable lifestyle. The therapeutic control of the mechanisms of progression have also demonstrated that it could be possible to attenuate or even to stop the evolution towards kidney failure.