Top Scientific Advances In High Blood Pressure Research For 2011


As you know, the mission of the Council for High Blood Pressure Research (HBPR) is to foster excellence in high blood pressure research and education and achieve the association's objectives in the field of hypertension.

The HBPR Council holds an annual international scientific conference for presentations on basic and clinical hypertension research. The fall conference presentations are published in the American Heart Association's journal Hypertension.

Annually, AHA asks all of its Councils and science groups what, in their opinion, have been the most important advances in their respective fields within the past year. These top advances relevant to our Council have the potential for great impact.

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

HBPR Top Advances for 2011

Uncoupling the mechanisms of obesity and hypertension by targeting hypothalamic IKK-β and NF-κB
Purkayastha S, Zhang G, Cai D. Nat Med. 2011 Jun 5;17(7):883-7. doi: 10.1038/nm.2372.

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
Choi M, Scholl UI, Yue P, Björklund P, Zhao B, Nelson-Williams C, Ji W, Cho Y, Patel A, Men CJ, Lolis E, Wisgerhof MV, Geller DS, Mane S, Hellman P, Westin G, Åkerström G, Wang W, Carling T, Lifton RP. Science. 2011 Feb 11;331(6018):768-72.

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.

3   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.

4   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
Zhang MZ, Yao B, Wang S, Fan X, Wu G, Yang H, Yin H, Yang S, Harris RC. J Clin Invest. 2011 Jul;121(7):2845-54. doi: 10.1172/JCI57324. Epub 2011 Jun 23.

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
Shibata S, Mu S, Kawarazaki H, Muraoka K, Ishizawa K, Yoshida S, Kawarazaki W, Takeuchi M, Ayuzawa N, Miyoshi J, Takai Y, Ishikawa A, Shimosawa T, Ando K, Nagase M, Fujita T. J Clin Invest. 2011 Aug;121(8):3233-43. doi: 10.1172/JCI43124. Epub 2011 Jul 18.

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
Boulos N, Helle F, Dussaule JC, Placier S, Milliez P, Djudjaj S, Guerrot D, Joutel A, Ronco P, Boffa J, Chatziantoniou C. Hypertension. 2011; 57: 1176-1182 Published online before print April 25, 2011, doi: 10.1161/HYPERTENSIONAHA.111.170746.

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
Gurley SB, Riquier-Brison AD, Schnermann J, Sparks MA, et al. Cell Metab. 2011 Apr 6;13(4):469-75.

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
Yamazaki D, Tabara Y, Kita S, Hanada H, et al. Cell Metab. 2011 Aug 3;14(2):231-41.

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
Aronow WS, Fleg JL, Pepine CJ, Artinian NT, Bakris G, Brown AS, Ferdinand KC, Forciea MA, Frishman WH, Jaigobin C, Kostis JB, Mancia G, Oparil S, Ortiz E, Reisin E, Rich MW, Schocken DD, Weber MA, Wesley DJ, Harrington RA; ACCF Task Force. ACCF/AHA 2011 expert consensus document on hypertension in the elderly: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents. Circulation. 2011 May 31;123(21):2434-506

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
Lob HE, Vinh A, Li L, Blinder Y, Offermanns S, Harrison DG. Role of vascular extracellular superoxide dismutase in hypertension. Hypertension. 2011 Aug;58(2):232-9.

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.

Posted by Stacy AHA Science on Mar 12, 2012 5:31 PM America/Chicago