| Abstract | CILJ: Odrediti utjecaj terapije Losartanom na protokom potaknutu dilataciju (FID) u zdravih Sprague-Dawley štakora. MATERIJALI I METODE: Za istraživanje su korišteni zdravi muški Sprague-Dawley štakori te su podijeljeni u kontrolnu grupu (CTRL, N = 9) i CTRL + Losartan grupu (N = 10) koja je u vodi za piće primala 40 mg Losartana dnevno kroz 7 dana. Osmi dan životinje su žrtvovane. Prije anesteziranja kombinacijom ketamina (75 mg/kg) i midazolama (0,5 mg/kg), pokusne životinje se izvažu. Slijedila je dekapitacija i izolacija središnje moždane arterije te njeno postavljanje na sustav tlačnog miografa (The Myograph System, DMT) za primjenu metode protokom potaknute dilatacije. Arteriju smo postavili na komoricu, inkubirali ju 60 minuta pri tlaku Δ80 mmHg za procjenu bazalnog promjera. Nakon inkubacije, arterija je izložena protoku koji dobivamo istovremenim promjenama ulaznog i izlaznog tlaka uz tlačne gradijente Δ10, Δ20, Δ40, Δ60, Δ100 mmHg, te je nakon bazalnog mjerenja, mjerena dilatacija u prisutnosti acetilkolina (ACh) i natrijevog nitroprusida (SNP). Na kraju eksperimenta PSS otopina, koja je protokom stvarala gradijent tlaka, zamijenjena je PSS Ca-free otopinom zbog mjerenja maksimalnog promjera arterije. REZULTATI: Rezultati pokazuju smanjen dilatacijski odgovor na protokom potaknutu dilataciju i smanjenu osjetljivost na acetilkolin u eksperimentalnoj skupini, odnosno kod životinja koje su bile na terapiji Losartanom, u odnosu na kontrolnu skupinu zdravih netretiranih štakora. Odgovor na SNP, koji je izravni donor NO-a, bio je podjednak u obje skupine. ZAKLJUČAK: Istraživanjem smo dokazali kako Losartan smanjuje vazodilatacijski odgovor središnje moždane arterije na o endotelu ovisan stimulus, odnosno na protokom potaknutu dilataciju i acetilkolin. |
| Abstract (english) | AIM: Determine the effect of Losartan therapy on the flow-induced dilation (FID) in healthy Sprague-Dawley male rats. MATERIALS AND METHODS: Healthy male Sprague-Dawley rats were used for the study and they were divided into a control group (CTRL, N = 9) and a CTRL + Losartan group (N = 10), which received a daily dose of 40 mg of Losartan in their drinking water for 7 days. On the 8th day they were sacrificed. Prior to anesthesia with the combination of ketamine (75 mg/kg) and midazolam (0,5 mg/kg), the experimental animals were weighed. The middle cerebral artery was isolated and set for flow induced dilation measurements (on a pressure myograph system, The Myograph System, DMT). After the incubation (60 minutes at the pressure of Δ80 mmHg), the arteries were exposed to the flow, which is obtained by simultaneous changes of in-flow and out-flow pressure with pressure gradients of Δ10, Δ20, Δ40, Δ60, Δ100 mmHg. After the measurement of basal response, the vascular response was measured in the presence of acetylcholine (ACh) and sodium nitroprusside (SNP). At the end of the experiment, the PSS solution, which generated the pressure gradient through flow, was replaced by a PSS Ca-free solution for the purpose of measuring the maximum artery diameter. RESULTS: The results showed that the flow induced dilation was decreased in the experimental group of rats that were on Losartan therapy, and dilation to acetylcholine was also reduced in the group of Losartan treated rats, compared to the control group of healthy untreated rats. The response to the direct NO donor, sodium nitroprusside, was not significantly different between the tested groups. CONCLUSION: Losartan reduces the vasodilation response of the middle cerebral artery to the endothelium-dependent stimulus, that is, to the flow-induced dilation, as well acetylcholine. |
