Urocortin 2 in patients with hypertension treated with angiotensin converting enzyme inhibitors or angiotensin receptor blockers.

Urocortin 2 (Ucn2) - corticotropin-releasing hormone receptor 2 signalling has favourable effects in the cardiovascular system, including vasodilation, lowering of blood pressure and systemic peripheral resistance, increase in cardiac output and cardiac contractility, as well as cardioprotection against ischemia-reperfusion injury. Vasodilation and lowering of blood pressure seem to be very interesting and important effects, but their mechanism and interaction with the antihypertensive drugs have not been evaluated. The aim of the present study was to assess the relationship between Ucn2 concentration and antihypertensive therapy in patients with primary hypertension. We examined a group of 65 patients with primary hypertension receiving at least 3 antihypertensive drugs. In all of them plasma level of Ucn2, anthropometric measurements, biochemical tests, ambulatory blood pressure monitoring (ABPM), and echocardiography were performed. There were no differences in Ucn2 level related to beta-blockers, calcium channel blockers or diuretics, but we observed that in patients treated with angiotensin converting enzyme inhibitors (ACEI) (n = 52) serum Ucn2 levels were significantly higher than in patients treated with angiotensin-receptor blockers (ARBs) (n = 13) (10.93 versus 5.56 ng/mL; P < 0.05). Moreover, we did not observe any differences in terms of blood pressure on ABPM, biochemical measurements, left ventricular mass index, or presence of diabetes. In addition, in a small subgroup receiving alpha-blockers we also found a lower level of Ucn2, with coexisting higher systolic blood pressure at night, higher left ventricle mass index (LVMI) and more frequent occurrences of diabetes compared to non-alpha-blockers. Our findings suggest that the hypotensive action of renin-angiotensin-aldosterone system blockade may be related to the urocortin system. Ucn2 may be an important element in the mosaic of blood pressure-lowering factors in patients treated for essential hypertension.

Blood pressure and arterial stiffness in patients with high sodium intake in relation to sodium handling and left ventricular diastolic dysfunction status.

In a population with high sodium consumption, we assessed relation between brachial and central blood pressures, elastic properties of large arteries, echocardiographic left ventricular diastolic function and sodium reabsorption as fractional urinary lithium excretion in proximal (FELi) and fractional sodium reabsorption in distal tubules assessed using the endogenous lithium clearance. Mean±s.d. age of 131 treated hypertensive patients (66 men and 65 women) was 61.9±7.5 years. We found significant interaction between left ventricular diastolic function and FELi with respect to the values of brachial blood pressure: systolic (SBP), diastolic (DBP) and mean blood pressure (MBP) (all PINT<0.03). In patients with FELi below the median value and impaired left ventricular diastolic function, the values of SBP (149.3 vs 132.5 mm Hg; P=0.005), DBP (85.1 vs 76.1 mm Hg; P=0.001), MBP (106.5 vs 94.9 mm Hg; P=0.001), central SBP (SBPC) (137.4 vs 122.0 mm Hg; P=0.01), central DBP (DBPC) (84.8 vs 76.0 mm Hg; P=0.003), central MBP (MBPC) (106.9 vs 95.9 mm Hg; P=0.007), aortic pulse wave augmentation (18.0 vs 13.5 mm Hg; P=0.03), pulse wave velocity (14.6 vs 12.5 m s(-1); P=0.02) and central aortic pulse wave augmentation index (155.7% vs 140.9%; P=0.01) were significantly higher than in patients with normal left ventricular diastolic function. Such relationships were not observed in the entire group and patients with FELi above the median value. In the hypertensive population with high sodium intake, increased sodium reabsorption in proximal tubules may affect blood pressure parameters and arterial wall damage, thus contributing to the development of left ventricular diastolic function impairment.

Evolution of rheological properties of erythrocytes and left ventricular geometry in cardiovascular disease risk patients.

The evolution of rheological properties of erythrocytes and geometrical parameters of left ventricle during therapies aimed at reducing cardiovascular disease (CVD) risk has been investigated. The study group consisted of 29 individuals who were diagnosed with the presence of at least one CVD risk factor at the time of entry to the study. Appropriate therapies were applied and the patients were followed for two years. Two groups of patients could be distinguished. The first group consisted of 12 individuals who were rigorously applying the therapy and for whom blood pressure, total cholesterol, LDL and glucose returned to normal levels. The second group included 17 patients for whom the above mentioned parameters remained pathological in spite of the applied therapy. In the first group, erythrocyte deformability as well as LVMI improved: deformability increased on average by 17% (p < 0.025), whereas LVMI decreased by 8% but not in a statistically significant manner (p < 0.27). In the second group, the results indicate worsening of both hemorheological properties and left ventricular geometry: RBC deformability became lower by 15% (p < 0.00001) and LVMI increased by 18% although this change was not statistically significant (p < 0.19). The results indicate that blood rheology improves when the CVD risk is reduced by administered therapy and worsens when the risk increases. Similar behavior shows LVMI. It is very likely that left ventricular geometry is influenced by blood rheology.

Left ventricular geometry and rheological properties of erythrocytes in patients at cardiovascular disease risk.

The relationship between erythrocyte deformability and aggregability with left ventricular mass index has been examined in patients diagnosed with at least one cardiovascular risk factor but without ongoing coronary heart disease. The group consisted of 66 individuals, 30 men and 36 women, of the average age 57.7 years. For each patient, deformability and aggregability of red blood cells (RBCs) as well as end-diastolic left ventricle diameter (LVD), interventricular septum thickness (IVST) and posterior wall thickness (PWT) were measured. On the basis of the echocardiographical parameters and anthropometric data, left ventricular mass index (LVMI) was calculated. The analysis revealed statistically significant correlation between the LVMI and erythrocyte deformability and aggregability: the LVMI increases with decreasing deformability and is higher in patients with higher aggregability. This finding indicates that the worsening of RBC rheological properties is one of the main factors contributing to alterations of cardiac geometry through the increase of peripheral resistance which, in turn, significantly augments the heart afterload. Given that left ventricular hypertrophy (LVH) is a predictor of cardiovascular morbidity and mortality, the association between hemorheological parameters and left ventricular geometry may be important in clinical practice.

[The comparison of selected parameters of structure and function of the cardiovascular system in patients with functioning graft on maintenance hemodialysis during a one year period]. / Porównanie wybranych wskazników opisujacych strukture i funkcje ukladu krazenia u pacjentów po przeszczepieniu nerki oraz chorych hemodializowanych w okresie jednego roku.

Successful renal transplantation allows to correct most of the abnormalities that lead to cardiovascular system injury in chronic uremia. The aim of the present study was to analyze selected anatomical and functional parameters of the heart using echocardiography. The study was conducted prospectively in two groups of patients: 73 subjects with functioning graft and 53 patients on maintenance hemodialysis. Obtained results were compared between those two groups at the start of the study and later on after 6 and 12 months of follow-up. Post-transplant patients were included into the study 11 +/- 6.4 months after successful transplantation. Mean dialysis period prior to transplantation was 35 +/- 21 months. Patients in the control group were dialyzed for mean 54 +/- 25 months. The prevalence of various diseases of the cardiovascular system was equal in both groups of patients (most frequently diagnosed was hypertension). There was no difference in ejection fraction within groups during the whole study period, however the value of this parameter was higher among patients with functioning graft at the beginning of the study (p < 0.01) as well as after 6 and 12 months (p < 0.001) as compared to patients on dialysis. The prevalence of different morphological abnormalities of the heart, such as concentric hypertrophy, left ventricle dilatation, valve dysfunction as well as calcification of various structures, was equal in both groups of patients at the beginning of the study. In 87.7% of patients with functioning graft, left ventricle hypertrophy was diagnosed at the beginning of the study (mean LVMI value 176.9 +/- 55.5 g/m2) and this percentage decreased to 63% after 6 months (LVMI 155.8 +/- 60.3 g/m2; p < 0.001 vs. baseline) and 53.4% after 12 months (LVMI 141.6 +/- 62.1 g/m2; p < 0.001 vs. baseline). Regression of initial left ventricle hypertrophy, although less pronounced was also present among patients on maintenance dialysis. There was no difference in LVMI value between the studied groups at the beginning of the study, whereas after 6 and 12 months of observation it became significantly lower in patients with functioning graft (155.8 +/- 60.3 vs. 179.5 +/- 50.9 g/m2; p < 0.01 and 141.6 +/- 62.1 vs. 176.2 +/- 50.5 g/m2; p < 0.001). Based on obtained results we conclude that successful renal transplantation promotes the normalization of a number of echocardiographic parameters, especially leads to regression of left ventricle hypertrophy. Renal transplantation seems to be an optimal method of treatment in patients with end-stage renal failure, considering structure and function of the cardiovascular system.

Determination of AL01576 concentration in rat lenses and plasma by bioassay for aldose reductase activity measurements.

Investigations on the disposition of the highly effective aldose reductase inhibitor AL01576 were carried out in pigmented rats after oral dosing and topical administration of a 0.1% ophthalmic suspension by means of an assay modified from a previously described method measuring aldose reductase activity. The crude enzyme extract of pig lenses was used as a test system. From the activity remaining after addition of the plasma or lens extracts, the concentration could be determined since the inhibition constant (IC50) of AL01576 is known. With this procedure, the concentration of AL01576 in plasma and lenses of Brown-Norway rats given different doses of the drug for 42 consecutive days were determined and compared with a gas chromatographic assay technique. These data indicate that AL01576 is absorbed into the lens with a substantial portion redistributing into the lens following systemic delivery. Drug concentrations were correlated with efficacy measurements, though they were lower in an animal group treated with naphthalene to provoke cataract formation. In a second animal series with Brown-Norway rats over 5 days, AL01576 was administered three times per day to the right eye only. During the washout period, AL01576 had a long persistence in plasma and lenses following this short-term topical ocular administration.