RESUMO
Hypertension is a highly prevalent chronic disease and the major risk factor for cardiovascular diseases, the leading cause of death worldwide. Hypertension is characterized by an increased vascular tone determined by the contractile state of vascular smooth muscle cells that depends on intracellular calcium levels. The interplay of ion channels determine VSMCs membrane potential and thus intracellular calcium that controls the degree of contraction, vascular tone and blood pressure. Changes in ion channels expression and function have been linked to hypertension, but the mechanisms and molecular entities involved are not completely clear. Furthermore, the literature shows discrepancies regarding the contribution of different ion channels to hypertension probably due to differences both in the vascular preparation and in the model of hypertension employed. Animal models are essential to study this multifactorial disease but it is also critical to know their characteristics to interpret properly the results obtained. In this review we summarize previous studies, using the hypertensive mouse (BPH) and its normotensive control (BPN), focused on the identified changes in the expression and function of different families of ion channels. We will focus on L-type voltage-dependent Ca2+ channels (Cav1.2), canonical transient receptor potential channels and four different classes of K+ channels: voltage-activated (Kv), large conductance Ca2+-activated (BK), inward rectifiers (Kir) and ATP-sensitive (KATP) K+ channels. We will describe the role of these channels in hypertension and we will discuss the importance of integrating individual changes in a global context to understand the complex interplay of ion channels in hypertension.
RESUMO
BACKGROUND: Coronary arteries supply oxygen and nutrients to the heart. We evaluated the dynamics of microscopic damage throughout the ischemia-reperfusion process in the wall of coronary arteries following myocardial infarction (MI). METHODS: In a swine model of reperfused MI, animals were divided into one control and four MI groups: 90-min ischemia without reperfusion, or followed by one minute, one week or one month reperfusion. Left anterior descending (LAD; infarct-related artery) and control right coronary arteries (RCA) were isolated. Taking the balloon inflation region as a reference, we isolated the proximal and distal LAD areas, performing histological staining and immunohistochemistry. RESULTS: Although mild changes in tunica intima were observed during ischemia, an almost complete absence of endothelium, and abnormal breaks in the internal elastic layer were found post-revascularization. In tunica media, increased thickness was observed soon after reperfusion, whereas larger thickness, disorganized muscle cell distribution and edema were found one week after reperfusion. This damage was more pronounced in distal rather than proximal LAD, whereas no changes were detected in RCA. In the tunica adventitia, vasa vasorum density decayed during ischemia in both LAD regions, but was restored after one month. Leukocyte adhesion to the artery was observed post-revascularization, developing into a massive presence in the three layers one week post-reperfusion. CONCLUSIONS: Ischemia-reperfusion can itself induce damage in the wall of the epicardial coronary artery, becoming more pronounced in the region distal to balloon inflation. Exploring these abnormalities will provide insight into the pathophysiology of coronary circulation and MI.
