Top Scientific Advances In High Blood Pressure Research For 2011
Rhian Touyz, MBBCh, MSc (Med), PhD
Chair, Council on High Blood Pressure Research (HBPR)
Director of the Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow
Uncoupling the mechanisms of obesity and hypertension by targeting hypothalamic IKK-β and NF-κB
The study demonstrates how obesity-related hypertension and obesity per se can be dissociated by modification of signaling in the hypothalamus. It suggests an important target to treat obesity-related hypertension and possibly other forms of hypertension.
K+ channel mutations in adrenal aldosterone-producing adenomas and hereditary hypertension
The study describes mutations in a potassium channel gene that give rise to hyperaldosteronism. It provides clues to how aldosterone is regulated in adrenal health and disease.
Epigenetic modulation of the renal β-adrenergic-WNK4 pathway in salt-sensitive hypertension
Mu S, Shimosawa T, Ogura S, Wang H, Uetake Y, Kawakami-Mori F, Marumo T, Yatomi Y, Geller DS, Tanaka H, Fujita T. Nat Med. 2011 May;17(5):573-80. Epub 2011 Apr 17.
This study reports that WNK4, which regulates distal nephron sodium transporters, is downregulated by sympathetic nerve ß2 stimulation. This occurs by cAMP-mediated histone acetylation leading to negative gluococorticoid response element binding to the WNK4 promoter. This suggests that modulation of this system could be an approach in the treatment of salt-sensitive hypertension.
Serine-threonine kinase with-no-lysine 4 (WNK4) controls blood pressure via transient receptor potential canonical 3 (TRPC3) in the vasculature
Park HW, Kim JY, Choi SK, Lee YH, et al. Proc Natl Acad Sci U S A. 2011 June 28; 108(26): 10750–10755. Published online 2011 June 13. doi: 10.1073/pnas.1104271108
The authors make the new findings that WNK4 can be modulated arterial pressure by reducing calcium influx via TRPC3 in the vasculature, thereby providing a potentially new target for treating hypertension.
Intrarenal dopamine deficiency leads to hypertension and decreased longevity in mice
This study uses proximal tubule-specific knockout of aromatic amino acid decarboxylase to demonstrate that lack of proximal tubule dopamine leads to fluid retention, hypertension, renal injury and decreased lifespan.
Rac1 GTPase in rodent kidneys is essential for salt-sensitive hypertension via a mineralocorticoid receptor-dependent pathway
This study identifies Rac1 as being involved in salt-sensitive hypertension and that this interacts with aldosterone-dependent mechanisms.
Notch 3 is essential for regulation of the renal vascular tone
Notch3 may be playing an important role in the myogenic responses in the protection of target organs from hypertensive injury. Notch3-/- mice when infused with AngII developed renal injury despite lower BP compared to the wild type, suggesting enhanced transmission of systemic BP to the renal microvasculature. Defective regulation of cerebral blood flow has also been described in humans with mutations of Notch3.
AT1A angiotensin receptors in the renal proximal tubule regulate blood pressure
This paper suggests that effectively targeting epithelial functions of the proximal tubule of the kidney should be a useful therapeutic strategy in hypertension.
TRIC-A channels in vascular smooth muscle contribute to maintaining BP
TRIC-A single nucleotide polymorphisms could provide biomarkers for constitutional diagnosis and personalized medical treatment of hypertension, and TRIC-A channels contribute to maintenance of blood pressure.
HYVET Translation into Practice
This first of its kind document addressed therapeutic targets for patients aged 80 and older; medication, including antihypertensives; blood pressure monitoring; and encouragement of lifestyle changes.
Paradigm shift on extracellular SOD
This paper changes the paradigm previously believed that extracellular SOD was the major isoform involved in hypertension. The paper also highlights the importance of the CNS in BP regulation.
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