Search

Renovascular disease irrespective of the cause activates multiple pressor systems, most specifically the renin-angiotensin-aldosterone system (RAAS). This complex hormone system exerts several renal and vascular effects, and seminal studies have outlined the sentinel importance of this system in the context of renovascular disease. Experiments using Goldblatt's classic 2 kidneys-1-clip model generate the prototype of angiotensin-dependent hypertension (Laragh, Am J Hypertens 4:541S–545S, 1991; Pickering, Semin Nucl Med 19:79–88, 1989). In humans, numerous methods to assess the levels of these hormones in the plasma have been proposed to characterize the hemodynamic significance of renovascular disease and to provide guidance on who will benefit of revascularization. However, in recent years, many of these diagnostic methods have been abandoned due to complex work-up, relatively low sensitivity and specificity, and the advent of more reliable non-invasive imaging techniques (Covic and Gusbeth-Tatomir, Prog Cardiovasc Dis 52:204–208, 2009). Although one could argue that the pressure in identifying the pressors roles has decreased, since preservation of function has become the most predominant argument, still, characterization of the RAAS system is important since it may provide useful additional information, including those for important therapeutic decisions. Several screening laboratory tests have been proposed over the years to identify patients with renovascular hypertension. Some of these studies remain based on the identification of the activation of the RAAS system and some may depend on the comparison of the kidneys side-by-side assuming that one kidney is not affected. However, even under the best conditions, these studies are rarely more than 80 % sensitive or specific. As a result, their value as predictors depends greatly on the pretest probability of renovascular disease. Moreover, functional tests are heavily dependent upon test conditions, including volume status, sodium intake and antihypertensive medications, which can affect levels of this complex hormone system. [ABSTRACT FROM AUTHOR]

Renal artery stenosis, often associated with multiple atherosclerotic risk factors, is a common cause of secondary hypertension, exacerbates cardiovascular disease, and leads to chronic renal failure. Therefore, it is critically important to elucidate the mechanisms responsible for disease progression and develop effective therapeutic strategies to treat these patients. Animal models have been extensively used as an experimental platform to mimic many features of human renovascular disease, and provide valuable information to probe its pathophysiology and downstream kidney injury. This chapter summarizes different methods used to develop and evaluate animal models of renovascular disease, often applying the Goldblatt two-kidney one-clip hypertension (2K1C) model in murine to large animal models, such as swine and canine. Finally, this chapter will examine different methods to monitor pathophysiological changes in renovascular hypertensive animal models and the use of therapeutic interventions, such as renal revascularization. [ABSTRACT FROM AUTHOR]

The thiazolidinediones (TZDs) are agonists for peroxisome proliferator-activated receptor-ν (PPARν), and they promote insulin sensitization and improve dyslipidemia in patients with type 2 diabetes mellitus. PPARν is widely expressed, both in circulating and renal parenchymal cells. The TZDs are widely used clinically to improve metabolic syndrome, but may also have beneficial effects on progressive renal damage beyond diabetes. PPARν agonists also have direct benefits on progressive renal injury independent of altering the metabolic profile, including effects on inflammation and oxidative stress.Wewill reviewselected evidence of such actions of PPARν agonists beyond metabolism and examine interactions with other key pro-fibrotic mediators, including transforming growth factor-β (TGF-β) and the renin-angiotensin system (RAS). [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) influence many physiological processes including host defense, hormone biosynthesis, fertilization and cellular signaling. Increased ROS production has been implicated in various chronic diseases, including hypertension, atherosclerosis, diabetes and kidney disease. Oxidative stress may be both a cause and a consequence of hypertension. Although oxidative injury may not be the sole etiology, it amplifies blood pressure elevation in the presence of other prohypertensive factors, such as salt loading, activation of the renin-angiotensin system and sympathetic hyperactivity. Oxidative stress is a multisystem phenomenon in hypertension and involves the heart, kidneys, nervous system, and vessels. Compelling evidence indicates the importance of the vasculature in the pathophysiology of hypertension, and therefore much emphasis has been placed on the (patho)biology of ROS in the vascular system. A major source for cardiovascular and renal ROS is a family of nonphagocytic NAD(P)H oxidases, including the prototypic Nox2 homologue-based NAD(P)H oxidase, as well as other NAD(P)H oxidases, such as Nox1 and Nox4. Other possible sources include mitochondrial electron transport enzymes, xanthine oxidase, cyclooxygenase, lipoxygenase, and uncoupled nitric oxide synthase (NOS). NAD(P)H oxidase-derived ROS is important in regulating endothelial function and vascular tone, and oxidative stress is implicated in endothelial dysfunction, inflammation, hypertrophy, apoptosis, migration, fibrosis, angiogenesis, and rarefaction, important processes involved in vascular remodeling in hypertension. These findings have evoked considerable interest because of the possibilities that therapies targeted against nonphagocytic NAD(P)H oxidase to decrease ROS generation and/or strategies to increase nitric oxide (NO) availability and antioxidants may be useful in minimizing vascular injury and thereby prevent or regress target organ damage associated with hypertension. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) risk is increased even in the earliest stages of chronic kidney disease (CKD) and is comparable to that conferred by diabetes. The main causes of death from CVD in CKD patients are a specific form of cardiomyopathy and accelerated atherosclerosis. Although the causes of the high CV risk are not yet fully understood, the main factors responsible for both progression of kidney disease and CV risk are hypertension, dyslipidemia, activation of the renin-angiotensin system and sympathetic nervous system, retention of sodium and phosphate, and vitamin D deficiency. All these factors are susceptible to intervention. [ABSTRACT FROM AUTHOR]

An encyclopedia entry for the term "renin-angiotensin-aldosterone system" is presented. It generates the peptide hormone angiotensin II and subsequently the mineralocorticoid aldosterone which both exert considerable impact on blood pressure and fluid homeostasis and have prime etiologic and therapeutic significance for cardiovascular diseases.

A definition of the term "hypoaldosteronism" is presented. It refers to the deficiency of aldosterone. In line with the disease, renal secretion of potassium is reduced which causes hyperkalaemia. Moreover, hypoaldosteronism can be treated through the replacement of a mineralocorticoid like fludrocortisone.

A definition of the term "accelerated senescence" is presented. The term refers to the process of rapid terminal growth arrest and is accompanied by cell senescence. Senescence can be induced in normal cells by DNA damage or introduction of mutant renin-angiotensin system. It is also induced in tumor cells by different anti-cancer drugs or ionizing radiation.