1. In human sympathetic denervation due to primary autonomic failure, food and exercise in combination may produce a cumulative blood pressure lowering effect due to simultaneous splanchnic and skeletal muscle dilatation unopposed by corrective cardiovascular reflexes. We studied 12 patients with autonomic failure during and after 9 min of supine exercise, when fasted and after a liquid meal. Standing blood pressure was also measured before and after exercise. 2. When fasted, blood pressure fell during exercise from 162 +/- 7/92 +/- 4 to 129 +/- 9/70 +/- 5 mmHg (mean arterial pressure by 22 +/- 5%), P < 0.0005. After the meal, blood pressure fell from 159 +/- 8/88 +/- 6 to 129 +/- 6/70 +/- 4 mmHg (mean arterial pressure by 22 +/- 3%), P < 0.0001, and further during exercise to 123 +/- 6/61 +/- 3 mmHg (mean arterial pressure by 9 +/- 3%), P < 0.01. The stroke distance-heart rate product, an index of cardiac output, did not change after the meal. During exercise, changes in the stroke distance-heart rate product were greater when fasted. 3. Resting forearm and calf vascular resistance were higher when fasted. Calf vascular resistance fell further after exercise when fasted. Resting superior mesenteric artery vascular resistance was lower when fed; 0.19 +/- 0.02 compared with 0.32 +/- 0.06, P < 0.05. After exercise, superior mesenteric artery vascular resistance had risen by 82%, to 0.53 +/- 0.12, P < 0.05 (fasted) and by 47%, to 0.29 +/- 0.05, P < 0.05 (fed). 4. On standing, absolute levels of blood pressure were higher when fasted [83 +/- 7/52 +/- 7 compared with 71 +/- 2/41 +/- 3 (fed), each P < 0.05]. Subjects were more symptomatic on standing post-exercise when fed. 5. In human sympathetic denervation, exercise in the fed state lowered blood pressure further than when fasted and worsened symptoms of postural hypotension.
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Adv Sci (Weinh)
January 2025
Department of General Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, 710038, P. R. China.
Leaky and structurally abnormal blood vessels and increased pressure in the tumor interstitium reduce the infiltration of CAR-T cells in solid tumors, including triple-negative breast cancer (TNBC). Furthermore, high burden of tumor cells may cause reduction of infiltrating CAR-T cells and their functional exhaustion. In this study, various effector-to-target (E:T) ratio experiments are established to model the treatment using CAR-T cells in leukemia (high E:T ratio) and solid tumor (low E:T ratio).
View Article and Find Full Text PDFCirc Res
January 2025
Hypertension Research Laboratory, School of Biological Sciences (R.R.M., T.Z., E.D., L.X., A.B.-W., H.A.J., M.N., M.P., K.C.L., W.Q., J.A.O.D., F.Z.M.).
Background: Fermentation of dietary fiber by the gut microbiota leads to the production of metabolites called short-chain fatty acids, which lower blood pressure and exert cardioprotective effects. Short-chain fatty acids activate host signaling responses via the functionally redundant receptors GPR41 and GPR43, which are highly expressed by immune cells. Whether and how these receptors protect against hypertension or mediate the cardioprotective effects of dietary fiber remains unknown.
View Article and Find Full Text PDFHypertension
January 2025
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA (W.Z., D.H., M.A.M., Y.M.).
Background: Hypotensive episodes detected by 24-hour ambulatory blood pressure (BP) monitoring capture daily cumulative hypotensive stress and could be clinically relevant to cognitive impairment, but this relationship remains unclear.
Methods: We included participants from the Systolic Blood Pressure Intervention Trial (receiving intensive or standard BP treatment) who had 24-hour ambulatory BP monitoring measured near the 27-month visit and subsequent biannual cognitive assessments. We evaluated the associations of hypotensive episodes (defined as systolic BP drops of ≥20 mm Hg between 2 consecutive measurements that reached <100 mm Hg) and hypotensive duration (cumulative time of systolic BP <100 mm Hg) with subsequent cognitive function using adjusted linear mixed models.
Hypertension
January 2025
Department of Environmental Health, Life Science and Human Technology, Nara Women's University, Japan.
Background: Exposure to cold environments is linked to cold-induced hypertension due to activated sympathetic nerve activity (SNA) and arterial baroreceptor reflex dysfunction. However, direct measurement of SNA during cold-induced hypertension and changes in baroreflex control of SNA remain unexplored.
Methods: Chronically instrumented rats were exposed to cold temperatures (10 °C) over 4 days after a control period (24 °C), and renal and lumbar sympathetic nerve activities were simultaneously measured during cold-induced hypertension.
Hypertension
January 2025
John W. Deming Department of Medicine, Tulane University School of Medicine, New Orleans, LA (K.C.F.).
Background: Black individuals frequently present with resistant hypertension and disproportionately increased cardiovascular risk. We investigated the blood pressure (BP)-lowering effect of the dual endothelin receptor antagonist aprocitentan in Black individuals enrolled in the PRECISION study (Parallel-Group, Phase 3 Study with Aprocitentan in Subjects with Resistant Hypertension).
Methods: Patients with confirmed resistant hypertension were randomized to aprocitentan 12.
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