Levels of endothelial substances in patients with newly identified hypertension compared with healthy controls.

INTRODUCTION: Endothelial dysfunction occurs at the very beginning of hypertension. The primary goal of our study was to determine plasmatic levels of multiple endothelial substances in otherwise healthy patients with primary hypertension and compare them to healthy individuals. Secondary goals were to determine the change in NOx levels after initiation of treatment and to compare the NOx levels in patients with established resistant hypertension. MATERIALS AND METHODS: 87 consecutive patients were enrolled. In the exploratory cohort of 22 healthy and 28 hypertensive individuals, plasmatic levels of big endotelin-1, asymmetric dimethylarginin, osteopontin, oxidized LDL, 3-nitro-L-tyrosine, growth/differentiation factor 15, intercellular adhesion molecule, vascular cell adhesion molecule, tumor necrosis factor-α, vascular endothelial growth factor, interleukins -1ß, -6 and nitric oxide levels (NO, expressed as NOx) were determined. The remaining 27 individuals were used as a validation cohort. Ten patients with established resistant hypertension were enrolled from our Hypertension Clinic. RESULTS: There was a statistically significant difference in NOx levels between healthy controls and hypertensive patients/resistant hypertensive patients: 45.164 µmol/L ± 48.627 vs 17.763 µmol/L ± 10.333 (P=0.00004)/14.36 µmol/L ± 7.194 (P=0.00007). CONCLUSION: We identified a decrease in total NOx plasmatic levels in otherwise healthy patients with primary hypertension that was more profound in patients with resistant hypertension. Plasmatic levels of other determined endothelial substances did not differ among the groups. However, due to the significant variability of plasmatic NOx levels even in healthy controls and many factors that affect it, we cannot recommend it to be used to assess endothelial function routinely.

Endothelial function, its relation to arterial hypertension and the possibility of its modulation.

Endothelium has both a protective and a very complex para-, endo- and autocrine functions. Vascular tone is determined as a balance between the production of vasodilating and vasoconstrictive substances. Among the most important vasodilators are nitric oxide (NO), PGI2, endothelial-derived hyperpolarizing factor (EDHF), adenosine and others, among the most important vasoconstrictors, endothelin-1 and angiotensin-2. Therapeutic goal of improving endothelial secretory function should be maximizing production of vasodilators and minimizing production of vasoconstrictors. Improvement of endothelial function can be achieved most effectively by following a healthy lifestyle (changing the diet to a Mediterranean type, sufficient physical activity, weight reduction and smoking cessation) and by initiating the treatment with ACE inhibitors and statins, when indicated. Large number of trials have shown that all of these interventions improve the prognosis of patients and a part of this effect may be mediated by improving endothelial dysfunction. Key words: endothelial dysfunction - endothelium - hypertension.