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Age-related change of angiotensin receptor promotes hypertension

Heterodimerization of AT1R with P2Y6R along with age promotes angiotensin II-induced hypertension

Date:
January 19, 2016
Source:
National Institutes of Natural Sciences
Summary:
The purinergic P2Y6 receptor (P2Y6R) promoted angiotensin II-induced hypertension in mice, new research indicates. Furthermore, heterodimerization of angiotensin type 1 receptor with P2Y6R along with age promotes angiotensin II-induced hypertension.
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(a) Mean blood pressure of wild-type or P2Y6R(-/-) mice treated with or without angiotensin II. (b) Hematoxylin and eosin-stained images of aortae from wild-type or P2Y6R(-/-) mice treated with angiotensin II.
Credit: NINS/NIPS

Hypertension is a major risk factor of various diseases including stroke, heart failure, vascular disease, and kidney disease. Angiotensin II, which is produced by the renin-angiotensin system, primarily functions as a physiological regulator of blood pressure and cardiovascular homeostasis, but it also plays a major role in the pathogenesis of hypertension. In the aorta, angiotensin II promotes hypertrophy of vascular smooth muscle cells through angiotensin type 1 receptor (AT1R), resulting in hypertension by increasing arterial wall thickness and vascular resistance. Additionally, angiotensin II induces physiological proliferation of neonatal but not adult vascular smooth muscle cells. How vascular smooth muscle cells determine the responsiveness to angiotensin II under different developmental conditions is mostly unclear.

The Japanese research team, led by Professor Motohiro Nishida of National Institute for Physiological Sciences (NIPS), National Institutes of Natural Sciences (NINS), found that the purinergic P2Y6 receptor (P2Y6R) promoted angiotensin II-induced hypertension in mice. Mice with a deletion of P2Y6R attenuated an angiotensin II-induced increase in blood pressure and medial hypertrophy (Image 1). AT1R and P2Y6R formed stable heterodimers. P2Y6R antagonist MRS2578 disrupted heterodimer formation of AT1R and P2Y6R, and suppressed angiotensin II-induced hypertension in mice.

Furthermore, P2Y6R abundance was developmentally increased in vascular smooth muscle cells. The increased abundance of P2Y6R converted AT1R-stimulated signaling in vascular smooth muscle cells from proliferation to hypertrophy (Image 2). These results suggest that increased formation of AT1R-P2Y6R heterodimers with age may increase the likelihood of hypertension induced by angiotensin II.


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Journal Reference:

  1. A. Nishimura, C. Sunggip, H. Tozaki-Saitoh, T. Shimauchi, T. Numaga-Tomita, K. Hirano, T. Ide, J.-M. Boeynaems, H. Kurose, M. Tsuda, B. Robaye, K. Inoue, M. Nishida. Purinergic P2Y6 receptors heterodimerize with angiotensin AT1 receptors to promote angiotensin II-induced hypertension. Science Signaling, 2016; 9 (411): ra7 DOI: 10.1126/scisignal.aac9187

Cite This Page:

National Institutes of Natural Sciences. "Age-related change of angiotensin receptor promotes hypertension: Heterodimerization of AT1R with P2Y6R along with age promotes angiotensin II-induced hypertension." ScienceDaily. ScienceDaily, 19 January 2016. <www.sciencedaily.com/releases/2016/01/160119151131.htm>.
National Institutes of Natural Sciences. (2016, January 19). Age-related change of angiotensin receptor promotes hypertension: Heterodimerization of AT1R with P2Y6R along with age promotes angiotensin II-induced hypertension. ScienceDaily. Retrieved May 23, 2017 from www.sciencedaily.com/releases/2016/01/160119151131.htm
National Institutes of Natural Sciences. "Age-related change of angiotensin receptor promotes hypertension: Heterodimerization of AT1R with P2Y6R along with age promotes angiotensin II-induced hypertension." ScienceDaily. www.sciencedaily.com/releases/2016/01/160119151131.htm (accessed May 23, 2017).

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