Obesity is associated with increased salt sensitivity and hypertension, but the mechanisms underlying altered renal sodium handling remain unclear. The Na-Cl cotransporter (NCC) is a key regulator of sodium reabsorption in the distal convoluted tubule and is dynamically regulated in response to changes in electrolyte balance. This study investigated whether diet-induced obesity (DIO) alters NCC responsiveness to salt loading in vivo and explored the underlying mechanisms using an ex vivo kidney slice model. Male C57BL/6 J mice were fed either a control or a high-fat (HF) diet for 22 weeks, followed by 2 weeks of NaCl loading. HF-fed mice developed obesity, hyperglycemia, hyperinsulinemia, and elevated systolic blood pressure. Although NaCl loading increased urinary sodium excretion and decreased serum aldosterone in both control and obese mice, the increase in urinary sodium excretion was attenuated in obese mice, suggesting enhanced renal sodium reabsorption. In addition, NaCl loading reduced NCC phosphorylation in control mice, whereas this response was attenuated in DIO mice, with no change in total NCC expression. Notably, STE20/SPS1-related proline-alanine-rich protein kinase (SPAK) phosphorylation was not significantly different among groups. In ex vivo kidney slice experiments, high-concentration insulin attenuated the high-potassium-induced suppression of NCC phosphorylation, whereas high glucose had no effect. These findings suggest that DIO impairs the normal suppression of NCC activity in response to salt loading without affecting basal NCC expression. Ex vivo findings suggest that insulin may modulate NCC responsiveness, although whether this mechanism contributes to NCC regulation in vivo remains uncertain. Impaired NCC responsiveness may promote renal sodium retention and could represent one potential mechanism linking obesity to altered sodium handling and blood pressure regulation.
Taiwan, in common with other high-income East Asian societies, is experiencing rapid demographic aging. Hypertension is present in the majority of older adults and remains the leading modifiable determinant of cardiovascular morbidity and mortality in this population. Yet managing blood pressure (BP) in older adults differs qualitatively from managing it in younger patients: arterial stiffening, salt sensitivity, orthostatic BP dysregulation, atrial fibrillation, frailty, cognitive vulnerability, and multimorbidity collectively alter the benefit-harm balance in ways that conventional guidelines—designed predominantly around middle-aged trial populations—do not adequately capture. To address this gap, the Taiwan Hypertension Society (THS) published the 2026 Guidelines for the Management of Hypertension in Older Adults, endorsed by the Taiwan Society of Cardiology (TSOC), the Taiwan Association of Gerontology and Geriatrics (TAGG), and the Taiwan Society of Family Medicine (TSFM). The guideline comprises 63 actionable recommendations developed through PICO-formulated clinical questions, systematic evidence appraisal, and the GRADE approach, with structured expert consensus for areas of limited evidence. Key updates include a measurement-first framework centered on validated oscillometric devices and the 7-2-2 home BP monitoring (HBPM) protocol; age- and comorbidity-stratified systolic BP (SBP) targets with frailty-sensitive safeguards; structured lifestyle prescriptions packaged as the SP-ABCDE mnemonic; individualized pharmacological management with explicit deprescribing considerations; and dedicated sections on orthostatic hypotension, atrial fibrillation, cognitive impairment, and resistant hypertension. This article summarizes the major highlights and clinical implications of the 2026 THS Hypertension guideline for older adults. Key components of the 2026 Taiwan Hypertension Society (THS) Guidelines for the Management of Hypertension in Older Adults. The upper panels summarize the diagnostic and lifestyle foundations—including the 7-2-2 home blood pressure monitoring (HBPM) protocol and the SP-ABCDE lifestyle prescription—together with the age- and risk-stratified systolic blood pressure (SBP) targets. For the intensive-versus-standard target comparison, an SBP target of <130 mmHg is a Strong recommendation for general older adults aged 65–79 years but a Conditional recommendation for those aged ≥80 years; a more intensive target of <120 mmHg may be considered (Conditional recommendation) in high-risk older adults with two or more additional cardiovascular risk factors. The lower panels summarize precision targets and frailty safeguards—including individualized targets and deprescribing considerations in frail older adults—and emphasize accurate BP measurement as a patient-safety strategy, including screening for orthostatic hypotension to prevent falls and syncope. HBPM, home blood pressure monitoring; OH, orthostatic hypotension; SBP, systolic blood pressure.
