Avtor/Urednik		Lenasi, Helena
Naslov		Vpliv kalcijevega antagonista amplodipina na aktivnost sintaze dušikovega oksida v endoteliju arterij prašiča
Tip		monografija
Kraj izdaje		Ljubljana
Založnik		Medicinska fakulteta
Leto izdaje		2003
Obseg		str. 89
Jezik		slo
Abstrakt		Dihydropyridine (DHP) calcium antagonists are reported to increase the release of nitric oxide (NO) from native and cultured endothelial cells. Since endothelial cells do not express voltage-dependent Ca2+ channels, the cellular mechanisms underlying this phenomenon are unclear. Thus, the aim of our study was to investigate whether amlodipine, a Ca2+channel blocker is able to induce an endothelium-dependent, NO-mediated relaxation and to determine whether it can influence the activity of the endothelial NO synthase (eNOS) by altering its phosphorylation. In isolated, precontracted, endothelium-intact porcine coronary arteries, amlodipine elicited a NO-mediated relaxation and a leftward shift in the concentraction-relaxation curve to bradykinin. Furthermore, amlodipine increased the generation of NO from freshly isolated arterial segments, as detected by electron spin resonance spectroscopy and stimulated an increase in cyclic GMP levels in cultured endothelial cells. In unstimulated endothelial cells, eNOS was not phosphorylated on Ser1177 but was phosphorylated on Thr495 (the unactive form of the enzyme). Amlodipine elicited the phosphorylation of Ser1177 and attenuated Thr495 phosphorylation, with a time course similar to that of eNOS activation. The amlodipine-induced relaxation of porcine coronanary artery was attenuated by the B2 kinin receptor antagonist, icatibant, but this antagonist only partially inhibited amlodipine-induced changes in eNOS phosphorylation in cultured endothelial cells. Moreover, amlodipine elicited the NO-mediated relaxation of rat aortic rings which do not express the B2 receptor. Amlodipine time-dependently attenuated the phosphorylation of protein kinase C (PKC) which is known to be the active form of the enzyme, with a time course similar to the changes in eNOS phosphorylation, and prevented the phorbol-12-myristate-13-acetate (PMA)-induced activation of PKC. (Abstract truncated at 2000 characters).
Deskriptorji		ENDOTHELIUM, VASCULAR AMLODIPINE NITRIC-OXIDE SYNTHASE CORONARY VESSELS AORTA RATS, WISTAR NITRIC OXIDE BRADYKININ CYCLIC GMP PHOSPHORYLATION SERINE THREONINE VASODILATION SWINE BLOTTING, WESTERN ELECTRON SPIN RESONANCE SPECTROSCOPY CELL COUNT RADIOIMMUNOASSAY