In this study, we investigated whether MCC950, a recently-identified inhibitor of NLRP3 activity, reduces blood pressure (BP), renal inflammation, fibrosis and dysfunction in mice with established hypertension.
Most patients with HTN require combination therapy; however, β-adrenergic antagonists and AII type 1 receptor blockers have been considered less effective because of overlapping mechanisms of action.
The assembly and activation of NLRP3 inflammasome are linked to the pathogenesis of several cardiovascular disease risk factors, such as hypertension and diabetes, and their major consequences-myocardial remodeling.
We investigated the role of macrophage NLRP3 inflammasomes in engulfing and digesting microbes, a key macrophage function, and in early onset of hypertension-associated macrophage injury using biochemical analyses, gene silencing, molecular biotechnology, immunofluorescence, and microbiology.
Despite having higher renal expression of <i>Nlrp3, Casp-1</i> and <i>Il-1β</i>, Ang II-induced hypertension (SBP: 139±7 mmHg) was unaffected by co-infusion of the NLRP3 inflammasome inhibitor, MCC950 (10 mg/kg/d; SBP: 145±10 mmHg).
The present study was designed to determine the roles and mechanisms of NLRP3 inflammasome in phenotypic modulation and proliferation of vascular smooth muscle cells (VSMCs) in hypertension.
NLRP3 inflammasome activation contributes to Ang II-induced VSMC phenotypic transformation and proliferation as well as vascular remodeling and hypertension.
Recent studies suggest that NALP3 and CARD-8 functional mutations contribute to the development of autoinflammatory diseases including hereditary periodic fever syndrome, arthritis as well as hypertension susceptibility.
In rats with AII-induced hypertension, acute rhRLX administration (up to 6 hours) significantly increased CO and ACg (24.9+/-3.9 and 34.3+/-12.6% above baseline, respectively) and significantly decreased SVR (17.2+/-3.5%) without changing MAP.
Approximately one half of the aldosterone-producing adenomas (APA) removed from patients with primary aldosteronism in the Hypertension Unit at Greenslopes Hospital belong to a subgroup in which aldosterone levels are responsive to the renin-angiotensin system (angiotensin-responsive APA; AII-R-APA), unlike classical APAs in which aldosterone is unresponsive (AII-U-APA).
These results could indicate that normotensive subjects with positive family histories of hypertension are characterized by an increased sensitivity to AII in the systemic and renal circulation as compared with subjects with negative family histories of hypertension.