Does leptin play a role in the pathogenesis of essential hypertension?

BACKGROUND: Leptin is produced and released by adipocytes in proportion to fat stores. Leptin as an anorectic hormone plays an important role in the regulation of food intake, energy expenditure, and insulin secretion. In contrast, neuropeptide Y, insulin, cortisol, and growth hormone are presumed to be appetite modulators. Leptin and neuropeptide Y are both involved in the activation of sympathetic tone. Increased body fat stores in obese patients are involved in the pathogenesis of some metabolic disorders (e.g., hyperinsulinaemia, glucose intolerance) and arterial hypertension. METHODS AND RESULTS: Based on this pathophysiological background, we tried to assess the relationship between plasma leptin and blood pressure in 41 patients with essential hypertension (EHP; 20 females, 21 males, mean age 38.7+/-1.9 years, mean body mass index - BMI - 25.8+/-0.5 kg/m2) and in an appropriately sex- and BMI-matched control group of 27 normotensive healthy subjects (NHS; 11 females, 16 males, mean age 39.7+/-2.5 years, mean BMI 24.8+/-0.6 kg/m2). The plasma leptin concentration did not differ significantly between EHP and NHS (13.0+/-1.9 vs. 8.1+/-1.0 ng/ml, respectively). In both groups a significant positive correlation was found between BMI and plasma leptin concentration (p<0.0001). A significant positive correlation (p<0.02) was found between leptinaemia and mean (MAP), systolic and diastolic blood pressures, if data were analyzed for all examined subjects or separately only for women. Such a correlation could not be confirmed for male NHS and EHP subjects. The plasma neuropeptide Y concentration was higher in EHP than in NHS (77.1+/-23.0 vs. 63.6+/-9.8pg/ml, p = 0.05). In contrast to neuropeptide Y plasma insulin, cortisol, and growth hormone concentrations were similar in EHP and in NHS. CONCLUSION: Both EHP and NHS are characterized by a positive correlation between BMI and leptinaemia. Leptin may be indirectly involved in blood pressure regulation, especially in women of both NHS and EHP.

Pathophysiological role of leptin in patients with chronic renal failure, in kidney transplant patients, in patients with essential hypertension, and in pregnant women with preeclampsia.

This paper is a summary of results obtained in our studies on leptinemia in patients with chronic renal failure treated with recombinant human erythropoietin (rHuEPO), in kidney transplant patients, in patients with essential hypertension, and in pregnant women with preeclampsia. In this study, we found that rHuEPO treatment has a suppressive effect on leptinemia in patients with endstage renal failure. These results suggest that the appetite stimulating effect of rHuEPO may be mediated by a reduction of leptin synthesis and release. At the early stage of successful kidney transplantation, a significant decline of leptinemia was noticed, which was not related either to the excretory function of the graft or the kind and dose of immunosuppressants. In kidney transplant patients with grafts functioning well for 2.5 years, significantly elevated leptinemia was found. From these results, we may conclude that factors other than the excretory function of the graft and the kind and dosage of immunosuppressants may be involved in the pathogenesis of abnormal leptinemia in these patients. Both in normotensive subjects and patients with essential hypertension, a positive correlation was found between leptinemia and mean blood pressure, suggesting that leptin may be involved in the regulation of blood pressure. Both healthy and preeclamptic pregnant women show higher leptinemia than nonpregnant women. In preeclamptic women, leptin levels in maternal vein blood, umbilical cord blood, and amniotic fluid were significantly higher than respective values found in healthy pregnant women. In contrast to healthy pregnant and nonpregnant women, in women with preeclampsia, no correlation was found between the body mass index (BMI) and leptinemia. In preeclamptic women the abnormally elevated leptinemia was not related to blood pressure. Finally, no correlation was found between leptinemia in maternal and umbilical cord blood. From these studies, it follows that the elucidation of abnormal leptin secretion in the pathogenesis of preeclampsia needs further study.

[Renin plasma profile and sodium sensitivity of blood pressure in hypertensive patients with or without a family history of hypertension]. / Profil reninowy osocza i sodowrazliwosc cisnienia tetniczego u chorych na nadcisnienie tetnicze z lub bez obciazajacego wywiadu rodzinnego w kierunku nadcisnienia tetniczego.

The relationship between sodium-sensitive hypertension, renin profile and genetic predisposition to hypertension have not been fully clarified. The present study aimed to establish the influence of family history of hypertension (at least one of the parents suffering from hypertension) on the renin profile, incidence of sodium-sensitivity of blood pressure and plasma concentration of selected biochemical parameters (creatinine, uric acid, glucose, sodium, potassium, calcium and cholesterol). 85 patients with essential hypertension (38 females, 47 males) were enrolled in the study. Secondary forms of hypertension were excluded in all patients by careful clinical and biochemical examination performed in the Department of Nephrology, Silesian University School of Medicine in Katowice. Plasma renin activity (PRA) was estimated twice: first after administration of a normal sodium diet (100-120 mmol of sodium per day) and 8 hours of supine position (PRA I) and a second time after 3 days of sodium restriction (10-20 mmol of sodium per day) and 3 hours of upright position (PRA II). All other biochemical parameters were measured once. Only patients with urinary sodium excretion lower than 60 mmol per day (after 3 days of low salt diet), were enrolled in the study. Sodium-sensitive hypertension was diagnosed in patients with a decrease of mean arterial blood pressure (MAP) of more or equal to 10 mm Hg after three days of sodium restriction. Reduction of MAP of less than 10 mm Hg was classified as sodium-nonsensitive hypertension. Among 85 patients with essential hypertension 49 (57.6%) had a positive (group I) while 36 (42.4%) a negative family history of hypertension (group II). Using the criteria presented in this study low, normal, high and rigid plasma renin activity were found, in 14.3%, 57.1%, 18.4% and 10.2% respectively of patients of group I. In patients of group II the incidence of the above mentioned renin profiles was similar: 13.9%, 58.3%, 19.4% and 8.4% respectively. In patients of group I 16 (32.7%) had sodium-sensitive and 33 (67.3%) sodium-nonsensitive hypertension, while in patients of group II 16 (44.4%) had sodium-sensitive and 20 (55.6%) sodium-nonsensitive hypertension (difference between group I and group II is statistically not significant). Patients of group I did not differ significantly from patients of group II with respect to : sex, age, blood pressure, sodium urinary excretion and plasma concentration of above mentioned parameters. From results obtained in this study we may conclude, that patients with and without history of essential hypertension do not differ with respect to renin plasma profile, incidence of sodium-sensitivity of blood pressure and other biochemical parameters.

[Requirement for blood in hemodialyzed patients with chronic renal failure in the period before and after introduction to erythropoietin (r-HuEPO) treatment]. / Zapotrzebowanie na krew u hemodializowanych chorych na przewlekla niewydolnosc nerek w okresie przed po wprowadzeniu do leczenia erytropoetyny (r-HuEPO).

The present paper aimed to assess the influence of EPO-therapy on the requirement of blood transfusion in haemodialysed patients with end-stage renal failure. As shown in this paper, introduction of r-HuEPO into the therapy of uraemic anaemia almost completely eliminated the request for blood transfusion in these patients. EPO therapy did not influence significantly to the serum creatinine concentration and mean arterial blood pressure in these patients.