Role of 20-HETE in nitric oxide synthase inhibition induced hypertension model

Hypertension is a disease, which has wide prevalence and serious complications nowadays, is worked on frequently. Studying with experimental animal models is beneficial for understanding the pathogenesis, ethiology and treatment of hypertension. İnhibition of nitric oxide synthase causes hypertension and endothelial dysfunction which indicates analog evidence with essantial hypertension. 20-hydroxyeicosatetraenoic acid (20-HETE) is a very important mediator which regulates vascular tone and blood pressure. It has been demonstrated in various experimental hypertension models that 20-HETE causes enhancement of periferic vascular resistance and effects blood pressure through changing the effects of various vasocontrictor and vasodilatator and causing endothelial dysfunction and oxydative stress. But these effects has not been studied on inhibition of nitric oxide synthase hypertansion mode yet. In the present study, we investigated the affects of 20-HETE on conductive and resistance arteries vasocontriction and vasodilation responses and blood pressure in nitric oxide synthase inhibition hypertension model. We planned two distinct studies which named as in vitro and in vivo (treatment) studies. In vitro study, control and hypertension groups were used. In treatment study; control, treatment, hypertension and hypertension+treatment groups were examined. In both studies, animals drinked water which contained 25 mg.kg-1.day-1 Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) during 5 weeks. Blood pressure of animals measured from tails with non-invasive method. In in vitro study, 20-HETE inhibitor N-Hydroxy-N'-(4-butly-2-methylphenyl)-formamidine (HET0016) added to tissue baths. In in vivo study, HET0016 enjected intraperitoneally at a dose of 10 mg.kg-1.day-1 to animals during last two weeks. At the end of experiment, aortic artery and third branch of mesenteric artery were isolated. They studied on tissue wire myographes. Results of studies showed parallelism. Blood pressure of hypertension group was significantly higher than control group.After administraton of HET0016 blood pressure of hypertension group attenuated significantly. Hypertension group of aortas showed increase with Phe mediated vasoconstriction and decrease with ACh mediated vasodilation. Both adding HET0016 to baths and enjections of HET0016 to animals ameliorated the responses. Neither KCl mediated vasocontriction nor SNP mediated vasodilation responses of aorta changed before or after HET0016 administration. KCl and Phe mediated vasoconstrictions of third branch of mesenteric arteries were similar in groups. Besides, they didn't changed after HET0016 administration. Hypertension group of mesenteric arteries showed decrease with ACh mediated vasodilation. Both adding HET0016 to baths and enjections to animals , corrected the responses. SNP responses were similar in groups. However, SNP mediated vasodilation responces in hypertension group were enhanced after adding HET0016 to baths or enjections to animals. In conclusion in nitric oxide synthase inhibition hypertension model, inhibition of 20-HETE significantly decreased high blood pressure. In conductive arteries inhibition of 20-HETE augmented the vasodilation and reduced the vasoconstriction responses. In resistance arteries, inhibition of 20-HETE caused increament in the endothelial depended and independent responses. We could say that 20-HETE inhibition related to vascular responses and blood pressure. Improving the vascular responses corrected the blood pressure.