Neurohumoral–renal interactions in blood pressure control

This issue of Acta Physiologica includes the first of a series of review articles summarizing the proceedings of the third conference on Neural, Hormonal and Renal Interactions in Blood Pressure Control, held from December 7–10, 2015 in the hill station of Mussoorie (Uttarakhand, India). The first two conferences were held in Samode (Rajasthan) in 2004 (Evans et al. 2005) and Mahabalipuram (Tamil Nadu) in 2008 (May & Evans 2010). The goal of these meetings has been to bring together experts in integrative cardiovascular biology to discuss the central questions that will drive future research in blood pressure control and the pathogenesis of hypertension in the coming decades. But these conferences have all been about more than just the science. They have also provided an opportunity for delegates to experience the rich and diverse culture and warm and hospitable peoples of India. Having experienced the wonders of the deserts of Rajasthan in 2004 and the seaside temples and rich Hindu culture of Mahabalipuram in 2008, we set off for the Gahwali Himalaya in 2015. The scientific programme included 35 oral presentations interspersed by sessions set aside for open discussion. The review articles in Acta Physiologica reflect the range of issues that were discussed in detail. Basically, most cases of hypertension, particularly of essential hypertension, are characterized by elevated peripheral resistance and normal cardiac output. The peripheral resistance vessel dysfunction can be primary or secondary. In the latter case, primary changes in brain or kidney functions may be the culprits providing ‘neurocentric’ and ‘renocentric’ concepts of the aetiology of hypertension. One of the major controversies in the debate between the renocentrics and the neurocentrics has been over the existence of alternative ‘brain baroreflex’ mechanisms, for example reflex control of arterial blood pressure driven by signals from sensors within the central nervous system itself. McBryde et al. discuss the various mechanisms that could underlie the putative ability of the brain to control arterial pressure via the function intracranial mechanoreceptors and chemoreceptors as well as through carotid body chemoreceptors (McBryde et al. 2016). Our understanding of the pathogenesis of hypertension is further complicated by the interactions between mother, placenta and foetus during critical windows in development that ‘programme’ later cardiovascular function in both child and mother (Paauw et al. 2016). Indeed, epigenetic factors render some of these programming effects intergenerational. Paauw et al. review this area and point the way forward to potential interventions that might be capable of ‘reprogramming’ cardiovascular function to reduce the risk of cardiovascular disease (Paauw et al. 2016). Bie and Evans attempt to reconcile the renocentric and neurocentric concepts that dominate our understanding of the pathogenesis of hypertension (Bie & Evans 2016). They identify aspects of these concepts that are at odds with each other, but also the increasing realizations that long-term control of blood pressure, both in normotension and hypertension, must be achieved through interaction between the brain and the kidney, and that essential hypertension sometimes is generated by primarily by the central nervous system, other times primarily by the kidney. Notably, details of specific molecular mechanisms responsible for the development of hypertension presently are available to a much larger extent in the kidney than in the brain. Often renal insufficiency is associated with hypertension due to dysfunction of the neurohumoral mechanisms of cardiovascular control. Underwood et al. (2016) focus on changes in neural activity driven by uraemic toxins via superoxide/nitric oxide imbalance and low-grade inflammation, and provide preliminary data in a rat model indicating augmented superoxide production within the hypothalamic paraventricular nucleus as a possible mediator of neurohumoral dysfunction. They suggest that this is but one example of mechanisms by which the uraemic state sensitizes CNS to sympathoexcitatory factors including renal afferent nerve inputs to the CNS and angiotensin II by the way of recruiting convergent superoxide-dependent and pro-inflammatory pathways. New targets for modulation of renal function, and thus cardiovascular function, continue to be identified. These include the inward rectifying potassium channels Kir4.1 and Kir5.1 (Palygin et al. 2016) which in the distal nephron appear to be critical elements of the regulation of the activity of the electroneutral sodium chloride cotransporter (NCC) and thus the interaction between NCC, the epithelial sodium channel (ENaC) and the renal outer medullary potassium channel (ROMK) in the physiological control of potassium excretion potentially explaining the effect