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INCREASING LEPTIN SENSITIVITY VIA PTP1B DELETION DOES NOT INCREASE BLOOD PRESSURE THROUGH AN INCREASED SYMPATHETIC TONE IN MICE ON A BALB/C BACKGROUND

Protein tyrosine phosphatase 1B (PTP1B) is a molecular brake on the leptin signaling pathway. Deletion of PTP1B increases leptin sensitivity and triggers hypertension in mice on a Balb/C background but not on a C57Bl/6 background. While leptin increases sympathetic tone (ST), whether PTP1B deletion differently increases ST in Balb/C and C57Bl/6 mice remains to be determined. To test the hypothesis that PTP1B deletion increases sympathetic tone in mice on the Balb/C background only, male and female wild‐type (WT) and knockout (KO) mice from both backgrounds were instrumented with jugular and carotid catheters to measure mean arterial pressure response to ganglionic blockade (mecamylamine) and adrenergic stimulation (phenylephrine). On the Balb/C background, PTP1B deletion increases sympathetic tone and reduces vascular adrenergic tone in both male (WT: −39±3% vs KO: −43±4%) and female mice (WT: −34±5% vs KO: − 35±4%). PTP1B deletion similarly increased ST in KO mice on the C57Bl/6 background (WT: 76±8% vs KO: 129±41%) but did not affect their adrenergic tone. Furthermore, in WT animals, sympathetic tone was higher in C57Bl/6 compared to Balb/c mice. Together these data suggest that the hypertension observed in PTP1B KO mice on the Balb/c background cannot be explained by an enhanced sympathetic tone.