HomeHypertensionVol. 64, No. 3Clinical Implications Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBClinical Implications Originally published1 Sep 2014https://doi.org/10.1161/HYPERTENSIONAHA.114.04247Hypertension. 2014;64:445Subjective Cognition in Patients With Hypertension (page 653)Subjective cognitive failures (SCF) are personal experiences of cognitive problems in everyday life and are a common feature in elderly people with cardiovascular disease. SCF can include perceptions of forgetfulness, slowness in performing simple tasks, or problems in planning or reasoning. It is not completely clear what these cognitive complaints represent. Strong associations between SCF and mood have been found. However, studies on the relationship with objective cognitive performance have shown inconsistent results. In addition, research on the association between SCF and imaging markers of cerebral small vessel disease is limited. In this issue of Hypertension, Uiterwijk et al show that SCF were related to objectively measured overall cognition, memory, and information processing speed. In addition, SCF were associated with the presence of cerebral microbleeds after adjustment for patient characteristics and vascular risk factors. These results provide important evidence that it is necessary to ask about the presence of cognitive complaints during consultation of patients with hypertension because SCF may point to lower objective cognitive function or cerebral microbleeds. Accordingly, this study emphasizes the importance of considering neuropsychological assessment and brain imaging when patients with hypertension report cognitive problems. Longitudinal studies in patients with hypertension are needed to examine whether SCF are predictive of cognitive decline over time.Autonomic Dysfunction in S-P467L Mice (page 590)Download figureDownload PowerPointPeroxisome proliferator-activated receptor-γ (PPARγ) is a ligand-activated transcription factor regulating adipogenesis and metabolism, and genetic data implicate PPARγ in human hypertension. S-P467L mice that specifically express a dominant-negative mutation (P467L) of PPARγ in vascular smooth muscle phenocopy the hypertension inpatients carrying the same mutation. In addition to hypertension, S-P467L mice exhibit impaired vasodilation, augmented vasoconstriction, and cerebral vascular remodeling. Interestingly, S-P467L mice also exhibit tachycardia suggesting baroreflex and autonomic dysfunction, a common feature in diabetes mellitus and predictor of cardiovascular events. In this issue of Hypertension, Borges et al used the S-P467L model to assess the role of vascular smooth muscle PPARγ in regulating baroreflex activity because activation of PPARγ increases baroreflex sensitivity in animals and human subjects, and diabetes mellitus is often associated with PPARγ impairment. S-P467L mice displayed increased sympathetic traffic to the heart and decreased baroreflex effectiveness. Aortic depressor nerve activity in response to increased arterial pressure was blunted in the transgenic mice (Figure), whereas the arterial pressure and heart rate responses to direct aortic depressor nerve stimulation were unaltered. Carotid arteries exhibited inward remodeling without a change in distensibility. These data suggest a defect in the afferent, with preservation of the central and efferent limbs of the baroreflex arc, caused by impaired vascular function, altered vascular structure, or compromised neurovascular coupling. These findings implicate vascular smooth muscle PPARγ as a critical determinant of neurovascular signaling. Because diabetes mellitus is often associated with PPARγ impairment, the study raises the possibility that diabetes mellitus–associated baroreflex alteration is as a result of defective vascular PPARγ and that S-P467L mice may be a useful model to understand the decreased baroreflex sensitivity in diabetes mellitus.Kir6.1 in Vascular Smooth Muscle (page 523)ATP-sensitive K+ channels (KATP) are sensitive to cellular metabolism and open in response to falling ATP and rising ADP levels. They are present in a diverse array of tissues and underlie several physiological processes including insulin release, cellular protection, and smooth muscle relaxation. They have a rich pharmacology with well-known inhibitors such as the antidiabetic sulphonylureas and a chemically diverse array of openers. Over the past 15 years, the molecular composition has been elucidated, and KATP channels are a hetero-octameric complex of a sulphonylurea receptor (SUR1, SUR2A, and SUR2B) and a Kir6.0 subunit, a member of the inwardly rectifying family of K+ channel. A series of murine models have been generated involving the global genetic deletion of these subunits to understand their physiological role. These mice have complex phenotypes that involve several different organ systems, and disentangling the influence of KATP in various tissues has proved difficult. For example, the global genetic deletion of Kir6.1 (kcnj8) leads to hypertension and cardiac arrhythmia potentially because of coronary artery spasm. In this issue of Hypertension, Aziz et al develop a model in which conditional genetic deletion of Kir6.1 is possible. Deletion specifically in vascular smooth muscle leads to hypertension but no sudden death, suggesting that Kir6.1-containing KATP in the endothelium or other tissues have an important role in cardiovascular (patho)physiology. The increased appreciation of the molecular and functional complexity of KATP may allow the development of therapeutic agents that are tissue specific and context dependent. Previous Back to top Next FiguresReferencesRelatedDetails September 2014Vol 64, Issue 3 Advertisement Article InformationMetrics © 2014 American Heart Association, Inc.https://doi.org/10.1161/HYPERTENSIONAHA.114.04247 Originally publishedSeptember 1, 2014 PDF download Advertisement
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Jul 5, 2023
Ibrahim M Salman 
Open Access