{'fraction_non_alphanumeric': 0.06532258064516129, 'fraction_numerical': 0.056451612903225805, 'mean_word_length': 4.223157894736842, 'pattern_counts': {'":': 0, '<': 3, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Abstract 169: Activation of The Interleukin-1 Receptor Contributes to the Pathogenesis of Angiotensin II-dependent Hypertension by Regulating Sodium Excretion


 Interleukin 1(IL-1) is an important regulator of inflammation and innate immunity and exerts diverse actions in multiple tissue beds. Previous studies have found increased renal IL-1 production in the setting of angiotensin (Ang) II-induced hypertension. The current study therefore explored whether activation of the IL-1 receptor (IL-1R) contributes to the pathogenesis of Ang II-dependent hypertension. Thus, we chronically infused uni-nephrectomized IL-1R-deficient (IL-1R KO) mice and wild-type (WT) controls (n=9 per group, 129/SvEv strain) with Ang II (1000ng/kg/min) for 4 weeks. At baseline, the mean arterial blood pressure (MAP) was similar in WT and IL-1R KO mice (131±9 vs. 125±6 mm Hg; p=NS). By contrast, after the 1st week of Ang II infusion, IL-1R KO mice had markedly attenuated elevations in BP (169±6 vs.184±3 mm Hg; p<0.05). Consistent with their lower BPs, IL-1R KO mice had smaller heart weight/body weight ratios compared to WTs after Ang II infusion for 14 days (7.4±0.2 vs. 6.7±0.3 mg/g, p=0.058) and 28 days (9.3±0.8 vs. 7.5±0.9 mg/g, p<0.001). Moreover, Ang II-infused IL-1R KOs had nearly 40% less albuminuria than WTs (5.9±0.9 vs. 9.4±1.4 mg/mg Cr; p=0.05). Consistent with reduced renal damage in the Ang II-infused IL-1R KOs, this group had lower renal mRNA expression of the kidney injury marker NGAL than Ang II-infused WTs (0.37±0.06 vs. 1.00±0.19 au; p=0.008) whereas expressions of IL-1α and β were similar in the 2 groups. Levels of urinary sodium excretion were similar in the groups at baseline and during the 1
 st
 week of Ang II when BPs were also similar. However, during the 2
 nd
 week of Ang II when BPs started to diverge between the groups, the IL-1R KOs excreted 23% more sodium than WT controls (416±23 vs. 337±25 μmol/day; p<0.04) while daily food intake was virtually identical in the groups throughout the experiment. As IL-1 has known vascular effects and renal blood flow can impact sodium excretion, we then examined acute pressor responses to Ang II (100ng) after 2 weeks of chronic Ang II infusion. The pressor response was blunted by 25% in IL-1R KOs compared to WT controls (30±2 vs. 41±4 mm Hg, p=0.04). We conclude that activation of the IL-1R potentiates Ang II-dependent hypertension by enhancing vasoconstriction and thereby limiting sodium excretion.
