Importance of the renal ion channel TRPM6 in the circadian secretion of renin to raise blood pressure.
Yosuke FunatoDaisuke YamazakiDaisuke OkuzakiNobuhiko YamamotoHiroaki MikiPublished in: Nature communications (2021)
Blood pressure has a daily pattern, with higher values in the active period. Its elevation at the onset of the active period substantially increases the risk of fatal cardiovascular events. Renin secretion stimulated by renal sympathetic neurons is considered essential to this process; however, its regulatory mechanism remains largely unknown. Here, we show the importance of transient receptor potential melastatin-related 6 (TRPM6), a Mg2+-permeable cation channel, in augmenting renin secretion in the active period. TRPM6 expression is significantly reduced in the distal convoluted tubule of hypotensive Cnnm2-deficient mice. We generate kidney-specific Trpm6-deficient mice and observe a decrease in blood pressure and a disappearance of its circadian variation. Consistently, renin secretion is not augmented in the active period. Furthermore, renin secretion after pharmacological activation of β-adrenoreceptor, the target of neuronal stimulation, is abrogated, and the receptor expression is decreased in renin-secreting cells. These results indicate crucial roles of TRPM6 in the circadian regulation of blood pressure.
Keyphrases
- blood pressure
- cardiovascular events
- angiotensin converting enzyme
- hypertensive patients
- heart rate
- coronary artery disease
- cardiovascular disease
- induced apoptosis
- poor prognosis
- angiotensin ii
- type diabetes
- spinal cord
- minimally invasive
- blood glucose
- signaling pathway
- oxidative stress
- long non coding rna
- risk assessment
- blood brain barrier
- binding protein
- brain injury
- drug induced
- glycemic control