The role of renal nerves in cardiovascular and renal function in normal and pathophysiological states.

Abstract

Video slideshow introduction to the Symposium by Symposium Speaker Clive May can be found here. The notion that increased sympathetic nervous system activity is important to trigger and maintain hypertension has been under consideration for decades. It is well known that an increase in renal sympathetic nerve activity (RSNA) stimulates renin secretion, which leads to renal vasoconstriction and increases sodium reabsorption (DiBona & Kopp, 1997), indicating that excessive RSNA will contribute to hypertension. Historically, surgical sympathectomy has been used to improve blood pressure control (Smithwick, 1940; Grimson, 1941). Nevertheless, this procedure was abandoned because of its high operative morbidity and mortality. Recently, however, catheter-based interventional strategies that interrupt the RSNA have shown promising results in providing a better long-term blood pressure control in patients with resistant arterial hypertension (Esler, 2010; Esler et al. 2010). These studies have raised enormous interest in understanding the role of renal nerves in the control of cardiovascular and renal functions. Nevertheless, the mechanisms underlying the initiation and maintenance of sympathoexcitation in pathophysiological conditions and how the renal denervation leads to a long-term reduction of blood pressure are not well understood. The symposium entitled ‘The Role of renal nerves in cardiovascular and renal function in normal and pathophysiological states’, which was held at The First Pan-American Congress of Physiological Sciences, Iguassu Falls, Brazil, 2–6 August 2014, focused on the new advances regarding the importance of efferent and afferent renal fibres on sodium homeostasis and the effects of renal denervation and reinnervation on cardiovascular and kidney functions. Regarding the mechanisms underlying sympathoexcitation in hypertension, the importance of increased oxidative stress in the paraventricular nucleus of hypothalamus and the rostral ventrolateral medulla for the autonomic dysfunction associated with renovascular hypertension was discussed (Campos et al. 2015). The effect of interaction between the sympathetic nervous system and angiotensin II on sodium reabsorption is a well-known classical mechanism for the maintenance of extracellular volume homeostasis; however, the underlying molecular signalling is not clearly understood. Recent data were presented in this symposium to demonstrate that renal nerve stimulation increases intrarenal angiotensin II and activates angiotensin II type 1 receptors, triggering a signalling cascade that leads to elevation of Na+–H+ exchanger isoform 3-mediated tubular transport. The findings enhance our understanding in relation to the interaction and synergism between the sympathetic nervous system and intrarenal angiotensin II actions in normal conditions (Bergamaschi et al. 2015). Additionally, the interaction between the brain and the kidneys to maintain homeostasis is still a matter of debate and was discussed in this symposium. Recent evidences suggest that increased RSNA and renal afferent nerve activity to the brain may contribute to the outcome to the disease, such as hypertension or heart failure (Nishi et al. 2014). During renovascular hypertension, increased afferent signalling from the ischaemic kidney may contribute to the increase in blood pressure. Indeed, in renovascular hypertensive rats submitted to treatment with bone marrow-derived mesenchymal stem cells, an improvement was found in the kidney tissue and function. This was accompanied by a reduction of sympathetic vasomotor activity to the kidneys and a reduction of blood pressure, probably as a consequence of reduced afferents from the diseased kidney (Oliveira-Sales et al. 2015). In another interesting recent study, the time course of the effects of renal denervation was investigated in sheep. In this study, 11 months after catheter-based radiofrequency renal denervation, functional and anatomical evidence of afferent and efferent renal nerve reinnervation were found. Therefore, the mechanism by which catheter-based renal denervation causes a prolonged decrease in blood pressure is not well understood. Further studies are required to address this important issue (Booth et al. 2015). In conclusion, the present symposium discussed new ideas about the mechanisms by which the brain and kidneys communicate and how they interact to maintain cardiovascular and renal homeostasis. Understanding the mechanisms of crosstalk between these two important organs (brain and kidneys) related to the control of blood pressure will probably increase the possibility of finding new strategies for the treatment of cardiovascular and renal diseases. Disclaimer: Supporting information has been peer-reviewed but not copyedited. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.