Molecular Interactions of Arterial Hypertension in Its Target Organs

Arterial hypertension (AH) is a major risk factor for the development of cardiovascular diseases. It is estimated that the disease affects between 10% and 20% of the adult population and is responsible for 5.8% of all deaths worldwide. Several pathophysiologic factors are crucial in AH, including inappropriate activation of the renin-angiotensin-aldosterone system, oxidative stress and inflammation. The heart, kidney, brain, retina and arterial blood vessels are prime targets of hypertensive damage. Uncontrolled and untreated AH accelerates the damage to these organs and could cause their failure. Damage to these organs could also manifest as coronary heart disease, cognitive impairment, retinopathy or optic neuropathy. For better understanding, it is important to analyze molecular factors which take part in pathogenesis of AH and hypertension-related target organ damage. In our paper, we would like to focus on molecular interactions of AH in the heart, blood vessels, brain and kidneys. We focus on matrix metalloproteinases, the role of immune system, the renin-angiotensin-aldosterone system and oxidative stress in hypertensive induced organ damage.     

Differential Expression of Sphingolipid Metabolizing Enzymes in Spontaneously Hypertensive Rats: A Possible Substrate for Susceptibility to Brain and Kidney Damage

Alterations in the metabolism of sphingolipids, a class of biologically active molecules in cell membranes with direct effect on vascular homeostasis, are increasingly recognized as important determinant in different vascular disorders. However, it is not clear whether sphingolipids are implicated in the pathogenesis of hypertension-related cerebrovascular and renal damage. In this study, we evaluated the existence of possible abnormalities related to the sphingolipid metabolism in the brain and kidneys of two well validated spontaneously hypertensive rat strains, the stroke-prone (SHRSP) and the stroke-resistant (SHRSR) models, as compared to the normotensive Wistar Kyoto (WKY) rat strain. Our results showed a global alteration in the metabolism of sphingolipids in both cerebral and renal tissues of both hypertensive strains as compared to the normotensive rat. However, few defects, such as reduced expression of enzymes involved in the metabolism/catabolism of sphingosine-1-phosphate and in the de novo biosynthetic pathways, were exclusively detected in the SHRSP. Although further studies are necessary to fully understand the significance of these findings, they suggest that defects in specific lipid molecules and/or their related metabolic pathways may likely contribute to the pathogenesis of hypertensive target organ damage and may eventually serve as future therapeutic targets to reduce the vascular consequences of hypertension.