dinoprost and lacidipine

Obesity is becoming one of the leading risk factors of coronary heart disease, hypertension, cerebrovascular disease. Despite the presence of a large number of antihypertensive agents and scientific substantiation of antihypertensive treatment principles it would be wrong to assume that the problem is completely solved. Development of endothelial dysfunction is one of the key pathogenic mechanisms in hypertension. This process is proven to have contributed by immune inflammation activation which is mediated by pro-inflammatory cytokines and oxidative stress.. To investigate the additional benefits of the combined antihypertensive therapy with lacidipine and candesartan on the basis of studying their antioxidant properties, impact on endothelial function and pro-inflammatory cytokines activity in hypertensive patients with overweight and obesity.. A combination of a calcium channel blocker and angiotensin receptor blocker (lacidipine 2 mg, 4 mg, and candesartan 4mg, 8mg, 16mg) was prescribed to 30 patients with essential hypertension of grades 1-3, 30 to 65 years old (mean age - 54.7 ± 5.8 years), who previously have not been receiving regular antihypertensive therapy.. During the course of combined antihypertensive therapy with lacidipine and candesartan, a significant reduction in i-NOS activity, TNF-α to its type I soluble receptor ratio (TNF- α/sTNF-αRI), and oxidative stress marker - 8-iso-PgF2α has been observed. Activity of e-NOS, levels of SOD and catalase, in contrast, have increased by the end of observation period.. The improvement of endothelial function due to lower level of oxidative stress and a significant decrease of immune activation has been observed in hypertensive patients with overweight and obesity under the influence of combined antihypertensive therapy with lacidipine and candesartan.

Topics: Adult; Aged; Antihypertensive Agents; Benzimidazoles; Biphenyl Compounds; Case-Control Studies; Dihydropyridines; Dinoprost; Drug Therapy, Combination; Endothelium, Vascular; Female; Humans; Hypertension; Male; Middle Aged; Obesity; Tetrazoles; Tumor Necrosis Factor-alpha

Experiments were performed on perfused human middle cerebral artery (MCA) precontracted with prostaglandin F2a. Nifedipine, isradipine and lacidipine induced dose-dependent relaxant effects on MCA segments. Effects of nifedipine were rather similar on MCA segments with and without endothelium; however, responses of endothelium-denuded vessel segments to isradipine and especially lacidipine were lower than those of vessels with intact endothelium. The vasodilator effects of these agents, especially isradipine and lacidipine, on vessel segments with intact endothelium in the presence of a NO-synthase inhibitor, N-nitro-L-arginine, were significantly attenuated whereas a cyclooxygenase inhibitor, indomethacin, did not significantly alter vasodilator responses of MCA segments to all calcium antagonists tested. It is suggested that the endothelium modulates vascular relaxation to dihydropyridines by an enhancement of calcium antagonist actions by basally released EDRF/NO at the level of vascular smooth muscles or by a dihydropyridine-induced increase in the release of EDRF/NO.

Topics: Adult; Arginine; Calcium Channel Blockers; Cerebral Arteries; Cyclooxygenase Inhibitors; Dihydropyridines; Dinoprost; Dose-Response Relationship, Drug; Endothelium, Vascular; Enzyme Inhibitors; Humans; In Vitro Techniques; Indomethacin; Isradipine; Muscle Relaxation; Muscle, Smooth, Vascular; Nifedipine; Nitric Oxide; Nitric Oxide Synthase; Nitroarginine; Vasodilator Agents