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Published on: September 1, 2015
[ATP-sensitive potassium channels and changes in their functional activity during streptozocin-induced diabetes
R B Strutyns'kyĭ1, O O Moĭbenko, S M Pyvovar
1A.A. Bogomoletz Institute of Physiology, National Academy of Science of Ukraine, Kiev.
Abstract:
Attenuation in the vasodilatory effects of a new synthesized opener of ATP-sensitive K' channels on isolated aorta strips of rat has been shown under experimental (streptozocin-induced) diabetes mellitus. The level of that attenuation depended on the nature of initial vasoconstriction. The most pronounced decrease--43.34% as compared to the control responses in healthy rats, we observed after norepinephrine-induced vasoconstriction. Following preliminary angiothensin-induced vasoconstriction and potassium depolarization, attenuation in vasoconstriction was 20.37% and 22.4%, respectively. Norepinephrine inhibited vasodilator effects of phlocalin in the aorta of diabetic rats much more significantly, as compared to those after potassium depolarization. Inhibitory effects of angiothensin II in rats with diabetes mellitus did not differ from those in the control rats. At the same time, constrictory responses to biological active agents were preserved and they did not differ from those in control rats. We suggest that impairment in vascular reactivity under diabetes mellitus, at least in part, depends on the changes in the functioning of ATP-sensitive potassium channels.
Insights
Experimental diabetes mellitus impairs vasodilatory effects of ATP-sensitive K+ channel openers in rat aorta. This impairment is most significant following norepinephrine-induced vasoconstriction, suggesting altered channel function contributes to vascular dysfunction.
Area of Science:
- Pharmacology
- Cardiovascular Physiology
- Endocrinology
Background:
- Diabetes mellitus is associated with vascular dysfunction.
- ATP-sensitive potassium (K+) channels play a role in regulating vascular tone.
- Impaired function of these channels may contribute to diabetic vascular complications.
Purpose of the Study:
- To investigate the vasodilatory effects of a novel ATP-sensitive K+ channel opener in diabetic rat aorta.
- To determine if diabetes mellitus affects the efficacy of this opener.
- To explore the influence of different vasoconstrictive states on the observed effects.
Main Methods:
- Isolated rat aorta strips were used to assess vasodilatory responses.
- Experimental diabetes mellitus was induced using streptozocin.
- Vascular responses were measured following pre-constriction with norepinephrine, angiotensin II, or potassium depolarization.
- The effects of an ATP-sensitive K+ channel opener were evaluated under these conditions.
Main Results:
- The vasodilatory effect of the ATP-sensitive K+ channel opener was attenuated in diabetic rat aorta compared to controls.
- The degree of attenuation varied with the initial vasoconstrictive agent, being most pronounced after norepinephrine (43.34% decrease).
- Responses to angiotensin II and potassium depolarization showed less attenuation (20.37% and 22.4%, respectively).
- Constrictory responses to other agents remained preserved in diabetic rats.
Conclusions:
- Experimental diabetes mellitus significantly attenuates the vasodilatory effects of ATP-sensitive K+ channel openers in rat aorta.
- The degree of attenuation is dependent on the type of initial vasoconstriction.
- These findings suggest that altered ATP-sensitive potassium channel function contributes to vascular reactivity impairment in diabetes mellitus.
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