NADPH Oxidase 1 Mediates Endothelial Dysfunction and Hypertension in a Murine Model of Obesity

Figures

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  Figure 1. NOX1 deletion does not alter obesity-derived whole body metabolic derangement. Body weight (A) is unchanged intra-group, with the obese groups demonstrating a significant and marked increased in body weight. Further, fasting glucose (B) and Hba1c (C) are significantly elevated in the obese groups compared to lean controls. NOX1 deletion does not alter muscle mass (D) as gastrocnemius weight is significantly atrophied in both obese groups. n ≥ 5 for all groups. * p ≤ 0.05 versus HdbWNOX1 controls.

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  Figure 2. NOX1 deletion prevents obesity-induced hypertension. Figure 2 is the 5 day average of blood pressure indices recorded using in vivo radiotelemetry. Mean arterial pressure (A) is significantly elevated in obese control (KdbWNOX1) compared to the other groups. Heart rate (B) is unchanged between the four groups. Systolic (C) and diastolic pressure (D) show similar increases in the obese control. n = 5 for lean groups and 7–9 for obese groups. * p ≤ 0.05 versus HdbWNOX1 controls. # p ≤ 0.05 versus KdbWNOX1.

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  Figure 3. NOX1 deletion improves renal dynamics in the obese mouse. Metabolic cages were used to examine food and fluid intake in all groups. Food intake (A) was similar intra-group, albeit significantly elevated in the obese mice. Water consumption (B) and urine production (C) show significant polydipsia and polyuria in the obese control (KdbWNOX1). Daily sodium balance is maintained (D), as sodium excretion (E) remains similar intra-group and elevated in the obese groups. n ≥ 8 for all groups. Obese mice exhibited lesser overall activity (F), which was likewise unchanged intra-group. * p ≤ 0.05 versus HdbWNOX1 controls. # p ≤ 0.05 versus KdbWNOX1.

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  Figure 4. NOX1 deletion prevents obesity-derived increases in renal NOX1. Relevant NOX isoforms were examined in total renal homogenates. Panel (A) shows significant elevation of expression of NOX1 in the obese control (KdbWNOX1), with no significant change in NOX2 (B) or NOX 4 (C) expression. Additionally, NADPH oxidase activator 1 (NOXA1, (D)) is also upregulated in the obese control, with no significant changes in NOXO1 (E) expression. n = 5–6 for all groups. * p ≤ 0.05 versus HdbWNOX1 controls. # p ≤ 0.05 versus KdbWNOX1.

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  Figure 5. Pharmacologic inhibition of NOX1 with GKT771 rescues endothelial function in obese mice. Treatment with GKT771 rescued microvascular endothelial function in obese mice (A), with no appreciable effect on alpha-adrenergic constriction (B) or endothelial-independent vasodilation (C). Pharmacologic treatment did not alter resting internal diameter (D), maximum constriction to saturated KCl (E), or vascular tone (F). n = 5–6 for all groups. * p ≤ 0.05 versus HdbWNOX1 controls.