The influence of nitric compounds on the reactivity of the isolated bovine abdominal aorta in the presence of Lipopolysaccharide (LPS)

Abstract

Nitric compounds, such as glyceryl trinitrate (GTN) and sodium azide, are well known vasodilators. Their vasodilative effect is accomplished via nitric oxide (NO), released during the biotransformation of these compounds in vascular smooth muscle and endothelium. Lipopolysaccharides (LPS) are endotoxins derived from gram-negative bacteria. In the vascular system, LPS cause severe functional disorders, inducing excessive synthesis and release of NO from the vascular endothelium and smooth muscles. The fact that the effect of both nitrovasodilatators and LPS on blood vessels is mediated by nitric oxide prompted us to study their possible synergistic vasodilative interaction, i.e. we wanted to investigate if there is a functional relationship between the activity of nitric compounds and LPS on the bovine abdominal aorta. The experiments were conducted on isolated bovine abdominal aorta, incubated for 4 hours in an organ bath with Tyrode solution. Glyceryl trinitrate and sodium azide bring about a dose-dependent relaxation of isolated bovine abdominal aorta previously contracted with noradrenaline. With an EC50 of 1.531 x 10-9M ± 0.13, glyceryl trinitrate is a more potent relaxant than sodium azide whose EC50 is 2.322 x 10-9M ±0.02. In the presence of LPS, the maximal relaxant effect of GTN was intensified in contrast to the control relaxant effect of GTN on isolated bovine abdominal aorta. The relaxant effect of sodium azide in the presence of LPS was significantly intensified in contrast to the control relaxant effect of this nitric compound. The applied lipopolysaccharide definitely induced the production of NO, which, together with NO derived from nitric compounds (glyceryl trinitrate and sodium azide), caused greater maximal relaxation of the isolated blood vessel, i.e. pretreatment with LPS enhances the biotransformation of both nitric compounds; to a higher degree of sodium azide.

Nitro-jedinjenja, kao što su gliceril trinitrat (GTN) i natrijum azid su poznati vazodilatatori. Mehanizam njihovog vazodilatatornog delovanja odvija se preko azotnog oksida (NO), koji se oslobađa u toku biotransformacije ovih jedinjenja u glatkim mišićima i endotelu krvnih sudova. Lipopolisaharidi (LPS) su endotoksini poreklom iz gram-negativnih bakterija koji u vaskularnom sistemu, prouzrokuju teške funkcionalne poremećaje, tako što indukuju prekomernu sintezu i oslobađanje NO-a iz endotela i glatkih mišića krvnih sudova. Imajući u vidu da se delovanje nitrovazodilatatora, kao i LPS-a na krvne sudove, odigrava posredstvom azotnog oksida, želeli smo da ispitamo da li između njih postoji sinergističko vazodilatatorno dejstvo, odnosno da utvrdimo funkcionalnu povezanost u mehanizmu delovanja nitro-jedinjenja i LPS-a na abdominalnoj aorti govečeta. Eksperimenti su izvedeni na izolovanoj abdominalnoj aorti govečeta, koja je inkubirana 4 časa u vodenom kupatilu za izolovane organe sa Tyrode-ovim rastvorom. Gliceril trinitrat i natrijum azid prouzrokuju dozno-zavisnu relaksaciju prethodno noradrenalinom kontrahovane izolovane abdominalne aorte govečeta. Gliceril trinitrat je potentniji i prouzrokuje jače relaksantno delovanje jer mu je EC50=1-531 x 10-9M±0.13 u odnosu na natrijum azid, čija je EC50=2.322 x 10 M±0.02. U prisustvu LPS-a maksimalan relaksantni efekat GTN-a je potenciran u odnosu na kontrolni relaksantni efekat GTN-a, na izolovanoj abdominalnoj aorti govečeta. Relaksantni efekat natrijum azida u prisustvu LPS-a je izrazito potenciran, u odnosu na kontrolni relaksantni efekat ovog nitro-jedinjenja. Primenjeni lipopolisaharid je indukovao produkciju NO-a, koji zajedno sa NO-om poreklom iz nitro-jedinjenja (gliceril trinitrata i natrijum azida) prouzrokuje jaču maksimalnu relaksaciju izolovanog krvnog suda, odnosno pretretman sa LPS-om povećava biotransformaciju oba nitro-jedinjenja, ali vise natrijum azida.