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1.
J Physiol Pharmacol ; 71(1)2020 Feb.
Article in English | MEDLINE | ID: mdl-32554847

ABSTRACT

Type 2 diabetes mellitus (T2DM) increases cardiovascular complications. Diabetic vascular dysfunction is associated with the reduced activity of the different smooth muscle potassium (K+) channels. Thus, the objective of our study was to investigate the role of the adenosine triphosphate (ATP)-sensitive K+ (KATP) channels in the relaxant effect of potassium channel opener, pinacidil on the human saphenous vein (HSV) obtained from the patients with and without T2DM. The rings of HSV without the endothelium, obtained from the patients who had undergone coronary bypass surgery, were mounted in an organ bath system and isometric tension was recorded. The relaxation of HSV, precontracted with phenylephrine, was produced by pinacidil. The expression of KATP subunits (Kir6.1, Kir6.2 and SUR2B) was detected by immunohistochemistry and Western blot. Pinacidil produces comparable effects on HSV in patients with and without T2DM. The suppression of pinacidil effect and its maximal relaxation by glibenclamide, selective blocker of KATP channels, was more pronounced on HSV in patients without T2DM. All three types of KATP subunits are expressed on the smooth muscle cells of HSV. While there are no differences in the expression of Kir6.1 and Kir6.2, the expression of SUR2B is lower in HSV in patients with T2DM. Pinacidil produced comparable KATP-dependent and -independent relaxation of the HSV in patients with/without T2DM. According to the effect of glibenclamide and the applied molecular analysis, presented findings demonstrated that diabetes mellitus was associated with the reduced expression of SUR2B subunit in the vascular smooth muscle of HSV.


Subject(s)
Diabetes Mellitus, Type 2/metabolism , KATP Channels/metabolism , Pinacidil/pharmacology , Saphenous Vein/drug effects , Vasodilation/drug effects , Vasodilator Agents/pharmacology , Aged , Diabetes Mellitus, Type 2/physiopathology , Dose-Response Relationship, Drug , Female , Humans , Male , Middle Aged , Organ Culture Techniques , Saphenous Vein/physiology , Vasodilation/physiology
2.
Exp Clin Endocrinol Diabetes ; 123(5): 303-7, 2015 May.
Article in English | MEDLINE | ID: mdl-25988879

ABSTRACT

Nitric oxide synthases (NOSs) and Na(+)/K(+)-ATPase are enzymes essential for regular functioning of the heart. Since both enzymes are under insulin and androgen regulation and since insulin action and androgen level were disturbed in polycystic ovary syndrome (PCOS), we hypothesized that cardiac nitric oxide (NO) production and sodium/potassium transport would be deteriorated in PCOS. To test our hypothesis we introduced animal model of PCOS based on dihydrotestosterone (DHT) treatment of female Wistar rats and analyzed protein expression, phosphorylation or subcellular localization of endothelial NOS (eNOS), inducible NOS (iNOS) and alpha subunits of Na(+)/K(+)-ATPase in the heart. Obtained results indicate that DHT treatment significantly decreased cardiac eNOS protein level and activating phosphorylation at serine 1,177, while inhibitory phosphorylation at threonine 495 was increased. In contrast to expression of eNOS, iNOS protein level in the heart of DHT-treated rats was significantly elevated. Furthermore, cardiac protein level of alpha 1 subunit of the ATPase, as well as its plasma membrane content, were decreased in rats with PCOS. In line with this, alpha 2 subunit protein level in fraction of plasma membranes was also significantly below control level. In conclusion, DHT treatment impaired effectiveness of NOSs and Na(+)/K(+)-ATPase in the female rat heart. Regarding the importance of NO production and sodium/potassium transport in the cardiac contraction and blood flow regulation, it implicates strong consequences of PCOS for heart functioning.


Subject(s)
Disease Models, Animal , Myocardium/enzymology , Nitric Oxide Synthase Type III/metabolism , Nitric Oxide Synthase Type II/metabolism , Polycystic Ovary Syndrome/enzymology , Sodium-Potassium-Exchanging ATPase/metabolism , Animals , Cell Membrane/enzymology , Cell Membrane/metabolism , Dihydrotestosterone , Down-Regulation , Female , Myocardium/metabolism , Phosphorylation , Polycystic Ovary Syndrome/metabolism , Protein Processing, Post-Translational , Protein Transport , Random Allocation , Rats, Wistar , Serine/metabolism , Threonine/metabolism , Up-Regulation
3.
Proc Biol Sci ; 268(1479): 1875-81, 2001 Sep 22.
Article in English | MEDLINE | ID: mdl-11564342

ABSTRACT

Prioritizing areas for conservation requires the use of surrogates for assessing overall patterns of biodiversity. Effective surrogates will reflect general biogeographical patterns and the evolutionary processes that have given rise to these and their efficiency is likely to be influenced by several factors, including the spatial scale of species turnover and the overall congruence of the biogeographical history. We examine patterns of surrogacy for insects, snails, one family of plants and vertebrates from rainforests of northeast Queensland, an area characterized by high endemicity and an underlying history of climate-induced vicariance. Nearly all taxa provided some level of prediction of the conservation values for others. However, despite an overall correlation of the patterns of species richness and complementarity, the efficiency of surrogacy was highly asymmetric; snails and insects were strong predictors of conservation priorities for vertebrates, but not vice versa. These results confirm predictions that taxon surrogates can be effective in highly diverse tropical systems where there is a strong history of vicariant biogeography, but also indicate that correlated patterns for species richness and/or complementarity do not guarantee that one taxon will be efficient as a surrogate for another. In our case, the highly diverse and narrowly distributed invertebrates were more efficient as predictors than the less diverse and more broadly distributed vertebrates.


Subject(s)
Biological Evolution , Ecosystem , Animals , Insecta , Rain , Snails , Trees , Vertebrates
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