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The Role Of Calcium-Activated Potassium Channels 2.3 (KCa 2.3) In The Inhibition Of Endothelin-1 (ET-1)-Induced NLRP3 Activation And Impairment Of The Erectile Function In DOCA/Salt Model Of Arterial Hypertension
Erectile dysfunction (ED) is often associated with risk factors for the development of cardiovascular diseases such as arterial hypertension. Arterial hypertension is a public health problem because it is an important risk factor for the development of other cardiovascular, cerebrovascular and renal diseases. In addition, ED occurs twice as frequent as in patients with arterial hypertension compared to normotensive patients. Vascular damage in arterial hypertension occurs in part due to impaired endothelial function as well as increased inflammatory mediators. Besides that, several studies have shown that increased expression of inflammatory mediators are closely linked to the development of ED. The modulation of calcium activated potassium channel 2.3 (KCa 2.3) was proposed as an approach to restore endothelial function and inhibit the inflammatory process. Both ED and arterial hypertension are strongly influenced by the reduction in the activity of KCa 2.3 or by the overexpression of endothelin-1 (ET-1), which has contractile and pro-inflammatory effects. Increased nucleotide binding oligomerization domain (NOD) like receptor [NLR] containing pyrin domain 3 (NLRP3) receptor activity modulates the inflammatory process, promotes vascular damage, increase in blood pressure, cardiac and renal hypertrophy. Studies from our laboratory have shown that increased NLRP3 receptor activity, mediated by ET-1, promotes vascular changes, elevation in blood pressure, endothelial dysfunction and ED. However, the mechanisms by which ET-1 leads to the activation of NLRP3 are still unknown. Therefore, this study will test the hypothesis that ET-1 inhibits the activity of KCa 2,3 and this contributes to the activation of NLRP3 in DOCA/salt hypertension model.
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