The effects of endothelin and L-NAME on plasma uric acid and urea concentration in Wistar rats

Abstract

Effects of endothelins, which include vasoconstriction and vasodilatation are possible by different molecular mechanisms. Endothelins induce increased synthesis of nitric oxide which in turn inhibits the synthesis of endothelin. Changes in biochemical parameters connected with the increased and decreased synthesis of nitric oxide are not thoroughly examined yet. In a series of experiments we compared the effects of endothelin (ET-1) on the inhibition of nitric oxide synthase (NOS), as well as the effects of L-nitro arginin metal estar (L-NAME) on plasma urea and uric acid concentration. Experiments were performed on anesthetized female adult Wistar rats. The experimental groups received an i. v. bolus of ET-1, L-NAME or saline. All parameters, heamodynamic and biochemical, were measured before the animals were sacrificed. L-NAME increased the mean arterial pressure, decreased renal blood flow and increased vascular resistance in carotid and renal arteries and increased in plasma uric acid and urea concentrations. ET- 1 significantly decreased uric acid concentration in the plasma but did not effect plasma urea concentration compared to the control group. These differences show complex relations of nitric oxide with cellular signalization compared to the basic NO-cGMP pathway.

Efekti endotelina koji uključuju vazokonstrikciju I vazodilataciju ostvaruju se različitim molekularnim mehanizmima. Endotelin indukuje povećanu sintezu azotnog oksida za koji se smatra da povratno inhibira sintezu endotelina. Promene biohemijskih parametara vezanih za povećanu i smanjenu sintezu NO nisu dovoljno proučene. U ovom radu su upoređeni efekti endotelina (ET-1) i inhibitora NOS-a, L-NAME na koncentraciju mokraćne kiseline i uree u plazmi. Eksperimenti su izvedeni na anesteziranim odraslim NW pacovima, ženskog pola. Eksperimentalne životinje su u i.v. bolusu primale ET-1, L-NAME ili fiziološki rastvor. Svi hemodinamski i biohemijski parametri su mereni pre žrtvovanja. L-NAME dovodi do povećanja srednjeg arterijskog pritiska smanjenja renalnog protoka i povećanja vaskularnog otpora u karotidnoj i renalnoj arteriji i povećanja koncentracije mokraćne kiseline i uree u plazmi. ET-1 značajno smanjuje koncentraciju mokraćne kiseline u plazmi ali ne utiče na koncentraciju uree u odnosu na kontrolu. Ove razlike pokazuju kompleksnije relacije NO-a sa ćelijskom signalizacijom u odnosu na osnovni NO-cGMP put.