The rapidly increasing burden of hypertension is responsible for premature deaths from cardiovascular disease (CVD), renal disease, and stroke, with a tremendous public health and financial burden. Hypertension detection, treatment, and control vary worldwide; it is still low, particularly in low- and middle-income countries (LMICs). High blood pressure (BP) and CVD risk have a strong, linear, and independent association. They contribute to alarming numbers of all-cause and CVD deaths. A major culprit for increased hypertension is sympathetic activity, and further complications of hypertension are heart failure, ischemic heart disease (IHD), stroke, and renal failure. Now, antihypertensive interventions have emerged as a global public health priority to reduce BP-related morbidity and mortality. Calcium channel blockers (CCB) are highly effective vasodilators. and the most common drugs used for managing hypertension and CVD. Cilnidipine, with both L- and N-type calcium channel blocking activity, is a promising 4th generation CCB. It causes vasodilation via L-type calcium channel blockade and inhibits the sympathetic nervous system (SNS) via N-type calcium channel blockade. Cilnidipine, which acts as a dual L/N-type CCB, is linked to a reduced occurrence of pedal edema compared to amlodipine, which solely blocks L-type calcium channels. The antihypertensive properties of cilnidipine are very substantial, with low BP variability and long-acting properties. It is beneficial for hypertensive patients to deal with morning hypertension and for patients with abnormal nocturnal BP due to exaggerated sympathetic nerve activation. Besides its BP-lowering effect, it also exhibits organ protection via sympathetic nerve inhibition and renin-angiotensin-aldosterone system inhibition; it controls heart rate and proteinuria. Reno-protective, neuroprotective, and cardioprotective effects of cilnidipine have been well-documented and demonstrated.
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http://dx.doi.org/10.59556/japi.71.0400 | DOI Listing |
Sci Rep
December 2024
Department of Respiratory Medicine, Hunan Provincial People's Hospital (The First-Affiliated Hospital of Hunan Normal University), No. 61 Jiefang Xi Road, Changsha, Hunan, 410219, China.
Pulmonary arterial hypertension (PAH) is a serious medical condition that causes a failure in the right heart. Two-pore channel 2 (TPC2) is upregulated in PAH, but its roles in PAH remain largely unknown. Our investigation aims at the mechanisms by which TPC2 regulates PAH development.
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December 2024
Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), 61 Biopolis Drive, Proteos, Singapore, 138673, Republic of Singapore.
Signaling interplay between the histamine 1 receptor (H1R) and transient receptor potential cation channel subfamily V member 1 (TRPV1) in mediating histaminergic itch has been well-established in mammalian models, but whether this is conserved in humans remains to be confirmed due to the difficulties in obtaining human sensory neurons (SNs) for experimentation. Additionally, previously reported species-specific differences in TRPV1 function indicate that use of human SNs is vital for drug candidate screening to have a higher chance of identifying clinically effective TRPV1 antagonists. In this study, we built a histamine-dependent itch model using peripheral SNs derived from human induced pluripotent stem cells (hiPSC-SNs), which provides an accessible source of human SNs for pre-clinical drug screening.
View Article and Find Full Text PDFBiomed Pharmacother
December 2024
Department of Biology, University of Naples Federico II, Naples, Italy; Biogem, Istituto di Biologia e Genetica Molecolare, Ariano Irpino, AV, Italy.
Intracellular Ca homeostasis dysregulation, through the modulation of calcium permeable ion channels and transporters, is gaining attention in cancer research as an apoptosis evasion mechanism. Recently, we highlighted a prognostic role for several calcium permeable channels. Among them, here, we focused on the plasma membrane bidirectional Na/Ca exchanger SLC8A1.
View Article and Find Full Text PDFBehav Brain Funct
December 2024
Department of Pharmacology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan.
The large-conductance calcium- and voltage-activated potassium (BK) channels, encoded by the KCNMA1 gene, play important roles in neuronal function. Mutations in KCNMA1 have been found in patients with various neurodevelopmental features, including intellectual disability, autism spectrum disorder (ASD), or attention deficit hyperactivity disorder (ADHD). Previous studies of KCNMA1 knockout mice have suggested altered activity patterns and behavioral flexibility, but it remained unclear whether these changes primarily affect immediate behavioral adaptation or longer-term learning processes.
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December 2024
School of Biological Sciences, University of Utah, Salt Lake City, Utah, USA.
Voltage-gated potassium channels (VGKCs) comprise the largest and most complex families of ion channels. Approximately 70 genes encode VGKC alpha subunits, which assemble into functional tetrameric channel complexes. These subunits can also combine to form heteromeric channels, significantly expanding the potential diversity of VGKCs.
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