POSSIBLE MECHANISM OF DEVELOPMENT OF SALT SENSITIVE ESSENTIAL HYPERTENSION.

It has been known that salt-sensitivity of blood pressure is defined genetically as well as can be developed secondary to either decreased renal function or by influence of other environmental factors. The aim of the study was to evaluate the possible mechanism for the development of salt-sensitive essential hypertension in the population of Georgia. The Case-Control study included 185 subjects, 94 cases with Essential Hypertension stage I (JNC7) without prior antihypertensive treatment, and 91 controls. Salt-sensitivity test was used to divide both case and control groups into salt-sensitive (n=112) and salt-resistant (n=73) subgroups. Endogenous cardiotonic steroids, sodium and PRA were measured in blood and urine samples at the different sodium conditions. Determinations of circulating levels of endogenous sodium pump inhibitors and PRA were carried out using the ELISA and RIA methods. Descriptive statistics were used to analyze the data. Differences in variables between sodium conditions were assessed using paired t-tests. Salt-sensitivity was found in 60.5% of total population investigated, with higher frequency in females. Salt-sensitivity positively correlated with age in females (r=0.262, p<0.01). Statistically significant positive correlation was found between 24 hour urine sodium concentration changes and salt-sensitivity r=0.334, p<0.01. Significant negative correlation was found between salt-sensitivity and PRA. Since no significant correlations were found between BMI and salt-sensitivity, we assume that BMI and salt-sensitivity should be discussed as different independent risk factors for the development of Essential Hypertension. Significant correlation was found between changes in GFR in salt-sensitive cases and controls p<0.01. This can be explained with comparable hyperfiltration of the kidneys at high sodium load and discussed as early sign of hypertensive nephropathy in salt-sensitive individuals. At the high sodium condition Endogenous MBG and OU were high in salt-sensitive subjects compared to salt-resistant. These compounds decreased after low salt diet in salt-sensitive cases as well as controls but remained within the same level in salt-resistant individuals. MBG and OU levels positively correlated with SBP in salt-sensitive individuals but salt-resistant subjects didn't show any changes. Our results support the idea that chronic high sodium loading (>200 mmol) which is typical in traditional Georgian as well as other diets switch those humoral and pathophysiological mechanisms that can lead to the development of certain type of hypertension in salt-sensitive individuals. Salt intake reduction can prevent development of hypertension in salt-sensitive subjects, although hypertension develops in the salt-resistant individuals but by other mechanism such as RAAS.

ASSOSIATION OF ENDOGENOUS CARDIOTONIC STEROIDS WITH SALT-SENSITIVITY OF BLOOD PRESSURE IN GEORGIAN POPULATION.

This investigation differentiates types of essential hypertension in a Georgian population as well as describes endogenous cardiotonic steroids in salt-sensitive and salt-resistant subjects. This case control study included 185 subjects: 94 cases with stage 1 essential hypertension (JNC7) naïve to antihypertensive treatment, and 91 controls. A salt-sensitivity test was used to dichotomize case and control groups into salt-sensitive and salt-resistant subgroups. Blood and urine samples were obtained to categorize participants as consuming high and low salt diets. Endogenous cardiotonic steroids, sodium and plasma-renin activity (PRA) were measured in both samples at the different sodium conditions. Determinants of circulating levels of endogenous sodium pump inhibitors were carried out using the ELISA and RIA methods; PRA was assessed by radioimmunoassay. Descriptive statistics were used to analyze the data. Differences in variables between sodium conditions were assessed using paired t-tests. Salt-sensitivity was found in 60.5% of the total population investigated, with a higher proportion in females. A statistically significant positive correlation was found between salt-sensitivity and age in females (r=0.262, p<0.01), and with 24-hour urine sodium concentration changes (r=0.334, p<0.01). A significant negative correlation was found between salt-sensitivity and PRA. At the high sodium condition, endogenous MBG and OU were high in salt-sensitive subjects compared to those who were salt-resistant. These compounds decreased with a low-salt diet in both salt-sensitive cases and controls but remained the same in salt-resistant individuals. The MBG and OU levels positively correlated with systolic blood pressure in salt-sensitive individuals but no variability was evident among salt-resistant subjects. Our results show that MBG and OU levels start to increase at the normotensive stage and sustained high concentrations can lead to elevated systolic blood pressure, a risk factor for arterial hypertension in salt-sensitive subjects.

Salt-sensitivity in normotensive elderly.

Up to now little has been known about mechanisms of salt sensitivity as well as causes of increasing frequency of salt-sensitivity and its distribution in elderly population. Data regarding activation of renin-angiotensin-aldosterone system in the elderly are quite controversial . Number of studies showed increased plasma rennin activity (PRA) while others indicate decreased renin levels. The study aimed to assess salt-sensitivity in normotensive young and elderly men. and assess their renin profile. Salt sensitivity was assessed in normotensive 44 young and 58 elderly males. Salt sensitivity was assessed by the difference of mean arterial pressure (MAP) on high (200 mmol/day) vs. low (40 mmol/day) sodium diet. Plasma rennin activity (PRA) was assessed during both diets. High salt diet led to significant increase in systolic blood pressure and MAP only in salt-sensitive subjects with peak levels in the elderly. Only salt-resistant subjects responded adequately during high salt diet by decrease in PRA which was significantly lower compared to basal levels. In salt-sensitive groups, especially in the elderly, PRA decreased to a lesser extent. Final clarification of mechanisms of salt-sensitivity in normotensive elderly further investigations is needed.

Influence of nebivolol on endothelial dysfunction in salt-sensitive hypertension.

The study was aimed to assess influence of nebivolol (nebilet) on endothelial factors (NO and endothelin1) during treatment of salt-sensitive hypertensive patients. A total of 40 patients (18 females and 22 males, mean age 53,1+/-1,58 yrs) with mild (I stage) arterial hypertension (with diastolic pressure 90-99 mm Hg and/or systolic pressure 140-159 mm Hg) were studied. Twelve age matched healthy subjects (4 women and 8 males) composed control group. Salt sensitivity was detected by M. Weir (1993) method. Patients were divided in two groups: salt sensitive hypertension (group I, 16 patients) and salt-resistant hypertension (group II, 24 patients). Nebivolol (Nebilet, Berlin-Chemie, Germany) was administered to 25 patients in dosage of 5 mg once a day during two weeks. Our studies have showed that ET-1 plasma levels were significantly elevated in patients with essential hypertension, while NO was markedly reduced compared to control group. NO levels were slightly lower in salt-sensitive hypertensives than in salt-resistant patients (p>0,05). ET-1 levels expressed opposite changes: in patients with salt-sensitive hypertension ET-1 levels almost twice exceeded those of salt-resistant patients (p<0,01). After treatment with nebivolol NO plasma level in salt-sensitive hypertensives significantly increased in Group I and did not change significantly in salt-resistant patients. Only slight decrease in ET-1 levels was detected in both groups after taking nebilet. Nebilet (nebivolol) treatment has an influence only on NO levels and appears to be the most effective in salt-sensitive hypertension.

Flow-mediated dilation in patients with left ventricular diastolic dysfunction.

The aim of the study was to evaluate the endothelium dependent FMD of the brachial artery in patients with LVDD. Endothelial function was assessed in 36 male patients (mean age 49+/-6 years) with LVDD due to CAD (22 patients) and essential hypertension (14 patients) as well as in 18 male patients (control group) without LVDD (12 patients with CAD and 6 with hypertension) of matched age. Our studies had showed significant decrease of FMD in patients with LVDD compared to those without LVDD (4.67%+/-1.68 vs. 6.12%+/-2.54, p<0.05). At the same time FMD in both groups appeared to be significantly lower than in healthy subjects. Post-ISDN vasodilation was almost similar in both groups of patients and lower than in controls. The post-ISDN vasodilatation did not differ regarding presence of LVDD or causative disease (CAD or arterial hypertension) and its extent was lower than in healthy controls. A weak correlation was found between FMD and post-ISDN vasodilatation (r=0.231, p>0.05). Data obtained suggest that endothelial dysfunction exists in patients with diastolic dysfunction. Based on these results it is considered that patients with early stages CAD and arterial hypertension depressed FMD might be indicator of LVDD.

Health-related interests of Georgian adolescents.

The aim of the study was to find out what adolescents in Georgia would like to know about health. Pupils of 6-10 grades (11-17 years old) (n=524) of the focus schools (secondary schools where FRESH program is being implemented) were investigated. A method of participatory research (so called social anthropologic approach) was applied. The study was anonymous. It yielded 3756 questions in total. The questions dedicated to health-related issues made up 36.8% for group I (11-13y.o.), 45,75% for group II (14-17y.o.), 40.5% -- total. The interest in different somatic and psychological problems and diseases was the same in both age groups (14,3%). Interest in sexual items was higher in later adolescents (group I -- 10.58+/-0.66%, group II -- 14.97+/-0.90%, p<0.05). Girls have shown more interest in diseases and common medical problems (M -- 27.3+/-3.2%, F - 45.2+/-2.6%; p<0.05). Boys were more interested in sexual behavior (M -- 40.2+/-3.6%, F -- 25.2+/-2.3%; p<0.05). There was shown a purposefullness of applied research methodology.