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Salt-sensitive (SS) hypertension is accompanied with severe cardiorenal complications. In this condition, elevated blood pressure (BP) resulting from salt retention is associated with counterintuitively lower levels of atrial natriuretic peptide (ANP). In plasma, ANP is degraded by the neprilysin; therefore, pharmacological inhibition of this metalloprotease (i.e., with sacubitril) can be employed to increase ANP level. We have shown earlier that sacubitril in combination with valsartan (75 μg/day each) had beneficial effects on renal function in Dahl SS rats. The goal of this study was to evaluate the effects of a higher dose of sacubitril on renal damage in this model. To induce hypertension, male Dahl SS rats were fed a 4% NaCl diet (HS) for 21 days, and were administered sacubitril (125 μg/day) or vehicle via s.c. osmotic pumps. At the end of the HS challenge, both groups exhibited similar outcomes for GFR, heart weight, plasma electrolytes, BUN, and creatinine. Sacubitril exacerbated kidney hypertrophy, but did not affect levels of renal fibrosis. We also observed aggravated glomerular lesions and increased formation of protein casts in the sacubitril-treated animals compared to controls. Thus, in Dahl SS rats, administration of sacubitril without renin-angiotensin-system blockage had adverse effects on renal disease progression, particularly in regards to glomerular damage and protein cast formation. We can speculate that while ANP levels are increased because of neprilysin inhibition, there are off-target effects of sacubitril, which are detrimental to renal function in the SS hypertensive state.

Sex differences (biological distinctions between males and females) present a complex interplay of genetic, developmental, biological, and environmental factors. More and more studies are shedding light on the importance of sex differences in normal physiology and susceptibility to cancer, cardiovascular and renal conditions, and neurodegenerative diseases. This mini-review is devoted to the role of sex dimorphisms in renal function, with a focus on the distinctions between male and female mitochondria. Here, we cover the aspects of renal mitochondrial bioenergetics where sex differences have been reported to date, for instance, biogenesis, reactive oxygen species production, and oxidative stress. Special attention is devoted to the effects of sex hormones, such as estrogen and testosterone, on mitochondrial bioenergetics in the kidney in physiology and pathophysiology.

Diuretics and renin-angiotensin system blockers are often insufficient to control the blood pressure (BP) in salt-sensitive (SS) subjects. Abundant data support the proposal that the level of atrial natriuretic peptide may correlate with the pathogenesis of SS hypertension. We hypothesized here that increasing atrial natriuretic peptide levels with sacubitril, combined with renin-angiotensin system blockage by valsartan, can be beneficial for alleviation of renal damage in a model of SS hypertension, the Dahl SS rat. To induce a BP increase, rats were challenged with a high-salt 4% NaCl diet for 21 days, and chronic administration of vehicle or low-dose sacubitril and/or valsartan (75 μg/day each) was performed. Urine flow, Na+ excretion, and water consumption were increased on the high-salt diet compared with the starting point (0.4% NaCl) in all groups but remained similar among the groups at the end of the protocol. Upon salt challenge, we observed a mild decrease in systolic BP and urinary neutrophil gelatinase-associated lipocalin levels (indicative of alleviated tubular damage) in the valsartan-treated groups. Sacubitril, as well as sacubitril/valsartan, attenuated the glomerular filtration rate decline induced by salt. Alleviation of protein cast formation and lower renal medullary fibrosis were observed in the sacubitril/valsartan- and valsartan-treated groups, but not when sacubitril alone was administered. Interestingly, proteinuria was mildly mitigated only in rats that received sacubitril/valsartan. Further studies of the effects of sacubitril/valsartan in the setting of SS hypertension, perhaps involving a higher dose of the drug, are warranted to determine if it can interfere with the progression of the disease.

Background It is unclear whether mental illness stigma affects individuals with subthreshold syndromes outside clinical settings. We therefore investigated the role of different stigma variables, including stigma-related stress and shame reactions, for avoidant stigma coping among members of the general population with elevated symptom levels. Methods Based on a representative population survey, general stress resilience, stigma variables, shame about having a mental illness as well as avoidant stigma coping (secrecy and social withdrawal) were assessed by self-report among 676 participants with elevated symptom levels. Stigma variables and resilience were examined as predictors of avoidant stigma coping in a path model. Results Increased stigma stress was predicted by lower general stress resilience as well as by higher levels of perceived stigma, group identification and perceived legitimacy of discrimination. More shame was associated with higher perceived legitimacy. Lower resilience as well as more perceived stigma, group identification and perceived legitimacy predicted avoidant coping. Stigma stress partly mediated effects of resilience, perceived stigma and group identification on avoidant coping; shame partly mediated effects of perceived legitimacy on coping. Stigma stress and shame were also directly and positively related to avoidant stigma coping. Analyses were adjusted for symptoms, neuroticism and sociodemographic variables. Conclusions Stigma may affect a larger proportion of the population than previously thought because stigma variables predicted secrecy and withdrawal among members of the general population with elevated, but overall mild symptom levels. Avoidant stigma coping likely has harmful effects, potentially exacerbating pre-existing psychological distress and undermining social networks. This highlights the need to reduce public stigma as well as to support individuals with subthreshold syndromes in their coping with stigma stress and shame reactions.

Our theory of ego structure starts from a holistic understanding: that psyche and soma form an inseparable unity, which is embedded in its surrounding groups, society, culture, religion, and nature. The skin is a sensory organ; it marks the boundary between ego and non-ego and forms the contact between inside and outside. In our holistic view of man in illness and health, culture and society, it is a part of human faculties to be creative, to further individual talents and abilities, and to react with illness, as well as to act sexually in the special way of one's ego structure. Therefore, we prefer to speak of psychodynamics of skin disease instead of psychosomatics.