Purinergic receptors in tubulointerstitial inflammatory cells: a pathophysiological mechanism of salt‐sensitive hypertension

Abstract

Recent studies have suggested that both the tubulointerstitial inflammatory cells and the activation of purinergic receptors integrate common mechanisms that result in salt-sensitive hypertension. The basis of this hypothesis is that renal endothelial cells release ATP in response to shear stress in the setting of hypertension. It has been demonstrated that the over-expression and activation of the P2X7, P2Y12 and P2X1 receptors favour the elevation of blood pressure induced by high-salt intake. In addition, the release of interleukins and inflammatory mediators in the tubulointerstitial area appears to be related to the activation of these receptors. Renal vasoconstriction and tubulointerstitial injury develop as a result, which increase sodium reabsorption by epithelial cells. Consistent with these effects, the reduction of tubulointerstitial inflammation caused by immunosuppressants, such as mycophenolate mofetil, prevents the development of salt-sensitive hypertension. Also, P2X7-receptor knockout mice develop minor renal injury when hypertension is induced via the administration of deoxycorticosterone acetate and a high-salt diet. In the setting of angiotensin II-induced hypertension, which is an early stage in the development of salt-sensitive hypertension, an acute blockade with the specific, non-selective P2 antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid prevented the renal vasoconstriction induced by angiotensin II. In addition, it normalized glomerular haemodynamics and restored sodium excretion to control values. These findings suggest that chronic administration of P2 purinergic antagonists may prevent the deleterious effects of purinergic receptors during the development of salt-sensitive hypertension.

Salt: a matter of balance

“…Purinergic signalling mechanisms (Franco et al 2015) (Mironova et al 2015) (Menzies et al 2015) are one hot topic, with adenosine signalling as a promising target for drug development (Chen et al 2013) (S€ allstr€ om et al 2014) (Kim et al 2015) (Welch 2015).…”

The renal and blood pressure response to low sodium diet in P2X4 receptor knockout mice

“…Normal renal function is essential for long‐term blood pressure (BP) regulation (Ivy and Bailey ), thus the P2 system is also a focus of hypertension research (Franco et al. ; Menzies et al. 2015a).…”

“…Indeed, abnormalities in the P2 system contribute to a range of renal diseases (Menzies et al 2017a), including diabetic nephropathy (Menzies et al 2017b). Normal renal function is essential for long-term blood pressure (BP) regulation (Ivy and Bailey 2014), thus the P2 system is also a focus of hypertension research (Franco et al 2015;Menzies et al 2015a).…”

Nephropathies

“…Franco et al . report that P2 purinergic receptors might play a role in the development of salt‐sensitive hypertension as well as angiotensin II‐induced hypertension, which also leads to the salt‐sensitive form . The usage of inflammatory modulators leads to a lower risk for hypertension.…”