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Studies have found that blood flow to the renal medulla is an important determinant of pressure-natriuresis and the long-term regulation of arterial pressure. First, a brief review of methods developed enabling the study of the medullary circulation is presented. Second, studies performed in rats are presented showing medullary blood flow plays a vital role in the pressure-natriuresis relationship and thereby in hypertension. Third, it is shown that chronic reduction of medullary blood flow results in hypertension and that enhancement of medullary blood flow reduces hypertension hereditary models of both salt-sensitive rats and salt-resistant forms of hypertension. The key role that medullary nitric oxide production plays in protecting this region from ischemic injury associated with circulating vasoconstrictor agents and reactive oxygen species is presented. The studies cited are largely the work of my students, research fellows, and colleagues with whom I have performed these studies dating from the late 1980s to more recent years. [ABSTRACT FROM AUTHOR]

This article explores the role of 20-HETE, a metabolite of arachidonic acid, in hypertension. Genetic studies and animal models have shown that 20-HETE is associated with hypertension, but the exact mechanisms are not fully understood. The study also highlights the link between mutations in certain genes that inhibit the production of 20-HETE and various health conditions such as hypertension, stroke, kidney disease, and cognitive dysfunction. However, conflicting findings regarding the effects of 20-HETE on blood pressure regulation suggest that further research is needed to fully understand its role in hypertension. [Extracted from the article]

Background: Hypertension is a leading risk factor for the development of Alzheimer's disease and Alzheimer's disease‐related dementia (AD/ADRD), which is closely linked with cerebral vascular inflammation and dysfunction. We previously found that high‐salt‐treated Dahl Salt‐Sensitive (SS) rats displayed blood‐brain barrier (BBB) leakage, astrocyte activation, neurodegeneration, and cognitive impairments. CD14 functions in the Toll‐like receptor 4 (TLR4) complex to initiate proinflammatory signaling events in response to LPS. CD14 levels were elevated in the brains of human and animal AD/ADRD models. This study aims to explore the vascular contribution of CD14 to AD/ADRD. Method: The expression of Cd14 was assessed through RT‐PCR in primary cerebral vascular smooth muscle cells (VSMCs) isolated from TgF344‐AD rats, and the results were compared to cells from control rats. The myogenic response of the middle cerebral artery (MCA) was compared between SS (SSCD14+/+), SSCD14‐/‐, and SD rats with and without the induction of hypertension with 4% NaCl diets. BBB function was detected by the leakage of injected Evans blue and fibrinogen. Brain cytokine levels were detected with Bio‐Plex Rat Cytokine 23‐Plex Assay. Result: Cd14 emerged as one of the significantly upregulated top genes in high‐salt‐fed SSCD14+/+ rats, with a subsequent three‐fold increase observed specifically in cerebral VSMCs of AD compared with control rats. Hypertensive SSCD14+/+ rats exhibited an impaired myogenic response of the MCA compared to normotensive SSCD14+/+ rats and SD rats fed with both high‐ and low‐salt diets. Notably, the deletion of CD14 demonstrated a remarkable trend in enhancing the myogenic response of the MCA in female SSCD14‐/‐ rats. Furthermore, high salt‐fed 24‐week SSCD14+/+ rats displayed BBB dysfunction. An augmented pan‐cytokine panel was observed in low salt‐fed 12‐week SSCD14+/+ rats, and this effect was magnified in high salt‐fed 24‐week SSCD14+/+ rats. Conclusion: These results collectively point to the potential role of CD14 in influencing vascular and immune responses, suggesting a link between CD14, hypertension, and cerebrovascular pathologies, particularly in the context of AD. Additional investigations are warranted to delve into the underlying mechanisms and ascertain whether CD14 exhibits a sex‐specific role in AD/ADRD. [ABSTRACT FROM AUTHOR]

Introduction One of the major complications of hypertension is nephropathy, which is associated with impaired renal vascular responsiveness and structural changes (1). The microvascular injuries are detected in the majority [...], Renal preglomerular arterioles regulate vascular tone to ensure a large pressure gradient over short distances, a function that is extremely important for maintaining renal microcirculation. Regulation of renal microvascular tone is impaired in salt-sensitive (SS) hypertension-induced nephropathy, but the molecular mechanisms contributing to this impairment remain elusive. Here, we assessed the contribution of the SH2 adaptor protein p66Shc (encoded by Shc1) in regulating renal vascular tone and the development of renal vascular dysfunction associated with hypertension-induced nephropathy. We generated a panel of mutant rat strains in which specific modifications of Shc1 were introduced into the Dahl SS rats. In SS rats, overexpression of p66Shc was linked to increased renal damage. Conversely, deletion of p66Shc from these rats restored the myogenic responsiveness of renal preglomerular arterioles ex vivo and promoted cellular contraction in primary vascular smooth muscle cells (SMCs) that were isolated from renal vessels. In primary SMCs, p66Shc restricted the activation of transient receptor potential cation channels to attenuate cytosolic [Ca.sup.2+] influx, implicating a mechanism by which overexpression of p66Shc impairs renal vascular reactivity. These results establish the adaptor protein p66Shc as a regulator of renal vascular tone and a driver of impaired renal vascular function in hypertension-induced nephropathy.