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    Effect of angiotensin II type 1 (AT1) receptor antagonist on the endothelial dysfunction in spontaneously hypertensive rats in correlation with the nitric oxide system
    (Comenius University, School of Medicine - AEPRESS SRO, 2003)
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    Korneti, Petar
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    Jovanoska, E
    Hypertension is associated with impaired endothelial function, which can be explained by a decrease in nitric oxide (NO) generation or by an enhanced inactivation of NO after its release from endothelial cells. The aim of this study was to investigate the effect of long-term treatment with losartan, an angiotensin II (AT1) receptor antagonist, on endothelial dysfunction in an animal model of hypertension in relation to the nitric oxide system. Losartan was administered to 48 sixteen-week-old spontaneously hypertensive rats, in a dose of 10 mg/kg bw/daily in drinking water, for 12 weeks. Systolic blood pressure (SBP) was measured at the beginning, after 4, 8 and 12 weeks of treatment, by the tail-cuff plethysmographic method. At each mentioned time point, a group of 12 animals was sacrificed and blood was withdrawn from the abdominal aorta. Plasma samples were used for determination of total nitrate/nitirite levels, cyclic guanosine monophosphate (cGMP) and endothelin (ET) 1 levels. Statistical evaluation of the results was performed by the use of a computer statistical programme Statistica for Windows 5.0. Losartan produced a significant decrease of SBP at all time points. On the other hand, long-term treatment with this AT1 receptor antagonist produced a significant increase of nitrate/nitrite and cGMP plasma levels. When we compared the values of SBP with plasma nitrate/nitrite as well as with cGMP values, a statistically significant correlation was established. A statistically significant decrease in plasma endothelin 1 values was found during the whole study period. Also, a positive correlation between SBP and plasma endothelin 1 concentrations was observed. Long-term losartan (AT1 receptor antagonist) treatment, apart from its blood pressure lowering effect in hypertension, has beneficial effects on the endothelial dysfunction which is at least partially due to the activation of the nitric oxide system. (Tab. 1, Fig. 2, Ref. 33.)
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    LOCAL NITRIC OXIDE SYNTHESIS IN THE VAGINA AND ITS IMPLICATION ON PREMATURE DELIVERY
    (Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, 2023)
    Albig, Jovana
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    Jovchevski, Sasha
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    Nitric oxide is a ubiquitous molecule involved in a range of physiologic and pathophysiologic processes, and is often at the centre of the scientific debate with its inherent complexity. Synthesised under the influence of its three isoenzymes, this molecule has been implicated in processes like inflammation, premature birth and carcinogenesis. Via comparative and experimental biochemical analysis of the cervical fluid of a group of patients with premature labour pains, using the indirect method of detection (the Griess spectrophotometric analysis), as well as analysis of the systemic inflammatory response, this study shows the association of nitric oxide with the premature births before the gestational week 34 as an independent marker for development of premature birth. It also showsthe association between the local nitric oxide synthesis in the vagina and the systemic inflammatory response and the significance of this association in the development of premature birth
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    Nebivolol: A Different Beta-Blocker for Hypertension
    (MedCrave, 2016-04)
    Otljanska, M
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    Otljanski, A
    Beta blockers are one of the classes of antihypertensive drugs, but there are controversies of their use as an initial therapy in treatment of arterial hypertension based on different guidelines for treatment of arterial hypertension. Nebivolol is a third generation, highly selective β-adrenoceptor antagonist with antihypertensive efficacy similar to other beta blockers but with unique function of increasing the release of nitric oxide (NO) via activation of β3-adrenergic receptors which improves endothelial function, produces vasodilatation, improves arterial compliance and reduces peripheral vascular resistance. Nebivolol highly selective lipophilic B1-adrenergic receptor antagonist and B3 agonist has different pharmacokinetics and pharmacodynamics profile from other beta blockers with more favourable metabolic and hemodynamic profile, like side effect profile, beta receptors blockade affinity, vasodilating properties, and improvement of endothelial function. Nebivolol has been show to be effective beta blocker for treatment of mild to moderate arterial hypertension as monotherapy or in combination therapy.