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Background and Aims In experimental investigations conducted in rats, raising serum uric acid (SUA) levels resulted in the stimulation of intrarenal renin expression. Studies in humans exploring the association of SUA with plasma renin activity (PRA) yielded conflicting results. Moreover, little is known about the relationship of SUA with plasma aldosterone concentration (PAC). The study aimed to assess the relationship between SUA levels, PRA, and PAC and the influence of age, gender, body mass index (BMI), and hyperuricemia on these relationships in subjects with essential hypertension (EH). Methods and Results We enrolled 372 hypertensive patients (mean age 45±12 years, men 67%) with uncomplicated EH that was not pharmacologically treated. The study population was divided in tertiles according to SUA levels. While PRA did not differ significantly across the three tertiles, PAC was higher in subjects belonging to the uppermost tertile of SUA than those in the lower ones (p=0.0429); however, this difference lost statistical significance after adjustment for age, sex, BMI, and serum creatinine. Univariate correlation analyses showed significant associations of SUA with PRA (r=0.137; p=0.008) and PAC (r=0.179; p&nbsp

Clinical and experimental data show an increase in sodium reabsorption on the proximal tubule (PT) in essential hypertension. It is well known that there is a link between essential hypertension and renal angiotensin II (Ang II). The present study was designed to examine ouabain-insensitive Na(+)-ATPase activity and its regulation by Ang II in spontaneously hypertensive rats (SHR). We observed that Na(+)-ATPase activity was enhanced in 14-week-old but not in 6-week-old SHR. The addition of Ang II from 10(-12) to 10(-6) mol/L decreased the enzyme activity in SHR to a level similar to that obtained in WKY. The Ang II inhibitory effect was completely reversed by a specific antagonist of AT(2) receptor, PD123319 (10(-8) mol/L) indicating that a system leading to activation of the enzyme in SHR is inhibited by AT(2)-mediated Ang II. Treatment of SHR with losartan for 10 weeks (weeks 4-14) prevents the increase in Na(+)-ATPase activity observed in 14-week-old SHR. These results indicate a correlation between AT(1) receptor activation in SHR and increased ouabain-insensitive Na(+)-ATPase activity. Our results open new possibilities towards our understanding of the pathophysiological mechanisms involved in the increased sodium reabsorption in PT found in essential hypertension.

The kidneys are centrally involved in the regulation of blood pressure. Kidney function requires the coordinated actions of a number of different vascular and tubular cell types in the renal vasculature and in the renal tubular system. The intrarenal coordination of these actions is not well understood. Since gap junctions have been identified in the kidneys, possible pathways involved in this context could be direct intercellular communication via gap junctions or via connexin hemichannels. In this context nine different connexins have been found to be expressed in the kidney, either localized to the vasculature or to the tubular system. Evidence is arising that malfunctions of certain connexins have an impact on the capability of the kidney to maintain blood pressure homeostasis. Findings reported in this context will be outlined and discussed in this review. This article is part of a Special Issue entitled: The Communicating junctions, composition, structure and characteristics.

The present study attempted to evaluate the effects of chronic intermittent hypoxia (CIH) associated with sleep restriction in hemodynamic parameters and the plasma renin–angiotensin system. Wistar–Hannover rats were submitted to isolated CIH exposure (1000–1600 h), sleep restriction (1600–1000 h), defined as 18-h paradoxical sleep deprivation followed by 6-h sleep permission period and CIH associated to sleep restriction for 21 days. The CIH and sleep restriction group showed a preferential increase in renal sympathetic nervous system (rSNA) associated with a reduction in plasma angiotensin (1–7) concentrations. However, CIH-sleep restriction rats did not modify rSNA and showed a higher angiotensin (1–7) concentration when compared to isolated CIH and sleep restriction. These results suggest that CIH and sleep restriction impaired the cardiovascular system, and its association to sleep loss can modify these effects by partially restoring circulating angiotensin (1–7).

Na(+)-transport regulating mechanisms classically considered to reflect renal control of sodium homeostasis and BP, i.e. aldosterone-mineralocorticoid receptors (MR)-epithelial sodium channels (ENaC)-Na(+)/K(+)-ATPase have now been demonstrated to also be present in the central nervous system. This pathway is being regulated independently of the peripheral/renal pathway and contributes to regulation of cerebrospinal fluid [Na(+)] by the choroid plexus, of brain tissue [Na(+)] by the ependyma and to neuronal responses to e.g. Na(+) or angiotensin II. Increases in CSF [Na(+)] by central infusion of Na(+)-rich aCSF or by high salt intake in Dahl S or SHR cause sympatho-excitation and hypertension. These responses appear to depend on activation of a CNS cascade starting with aldosterone-MR-ENaC-"ouabain," the latter lowering neuronal membrane potential leading to enhanced angiotensin II release in e.g. the PVN. Specific CNS blockade of any of the steps in this cascade from aldosterone synthase blockade to AT(1)-receptor blockade prevents the sympathetic hyperactivity and hypertension on high salt intake, irrespective of the presence of a "salt-sensitive kidney." We propose that in salt-sensitive hypertension an increase in CSF [Na(+)] causes a local increase in aldosterone biosynthesis which activates an aldosterone dependent neuromodulatory pathway which enhances activity of angiotensinergic sympatho-excitatory pathways leading to hypertension.