Abstract
Purinergic receptors play a central role in the renal pathophysiology of angiotensin II-induced hypertension, since elevated ATP chronically activates P2X7 receptors in this model. The changes induced by the P2X antagonist Brilliant blue G (BBG) in glomerular hemodynamics and in tubulointerstitial inflammation resulting from angiotensin II infusion were studied. Rats received angiotensin II (435 ng kg−1 min−1, 2 weeks) alone or in combination with BBG (50 mg/kg/day intraperitoneally). BBG did not modify hypertension (214.5 ± 1.4 vs. 212.7 ± 0.5 mmHg), but restored to near normal values afferent (7.03 ± 1.00 to 2.97 ± 0.27 dyn.s.cm−5) and efferent (2.62 ± 0.03 to 1.29 ± 0.09 dyn.s.cm−5) arteriolar resistances, glomerular plasma flow (79.23 ± 3.15 to 134.30 ± 1.11 nL/min), ultrafiltration coefficient (0.020 ± 0.002 to 0.036 ± 0.003 nL/min/mmHg) and single nephron glomerular filtration rate (22.28 ± 2.04 to 34.46 ± 1.54 nL/min). Angiotensin II induced overexpression of P2X7 receptors in renal tubular cells and in infiltrating T and B lymphocytes and macrophages. All inflammatory cells were increased by angiotensin II infusion and reduced by 20% to 50% (p < 0.05) by BBG administration. Increased IL-2, IL-6, TNFα, IL-1β, IL-18 and overexpression of NLRP3 inflammasome were induced by angiotensin II and suppressed by BBG. These studies suggest that P2X7 receptor-mediated renal vasoconstriction, tubulointerstitial inflammation and activation of NLRP3 inflammasome are associated with angiotensin II-induced hypertension.
Highlights
Renal tubulointerstitial inflammation is a consistent feature in angiotensin II-induced hypertension
In short-term angiotensin infusion, the inflammatory infiltration is critical in the subsequent development of salt-sensitive hypertension [1,2,3,4,5], whereas in the chronic angiotensin infusion, tubulointerstitial inflammation is a characteristic that impairs pressure natriuresis, maintains sodium retention and supports blood pressure increment [5]
The activation of purinergic receptors plays an important role in the pathophysiology of angiotensin II (Ang II)-induced hypertension, supporting the production of vasoactive mediators [14,15], sustaining the inflammatory response [16] and impairing pressure natriuresis [5]
Summary
Renal tubulointerstitial inflammation is a consistent feature in angiotensin II-induced hypertension. In short-term angiotensin infusion, the inflammatory infiltration is critical in the subsequent development of salt-sensitive hypertension [1,2,3,4,5], whereas in the chronic angiotensin infusion, tubulointerstitial inflammation is a characteristic that impairs pressure natriuresis, maintains sodium retention and supports blood pressure increment [5]. The activation of purinergic receptors plays an important role in the pathophysiology of angiotensin II (Ang II)-induced hypertension, supporting the production of vasoactive mediators [14,15], sustaining the inflammatory response [16] and impairing pressure natriuresis [5]. The activation of purinergic receptors by elevated concentrations of ATP has been shown in the development of salt-sensitive hypertension and Ang II-induced hypertension [17,18,19]. Purinergic receptors are central in the ATP-mediated activation of the nucleotide-binding oligomerization domain (NOD), leucine-rich repeat (LRR)-containing protein 3 (NLRP3) inflammasome [20,21,22,23,24,25]
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