Arginase inhibition augments reflex cutaneous vasodilation in essential hypertensive humans

Reflex cutaneous vasodilation (VD) is dependent on nitric oxide (NO), which is diminished in hypertension (HTN). Arginase preferentially metabolized L‐arginine (L‐arg) limiting NO synthesis through NOS and may be upregulated with HTN. We hypothesized that NO‐dependent VD would be attenuated, and arginase inhibition (A‐I) would augment VD, in HTN skin. Four microdialysis fibers were placed in skin of 7 unmedicated HTN (MAP: 112±1 mmHg) and 5 age‐matched normotensive (AMN) (MAP: 87±1 mmHg) humans: control (C: Ringers), NOS inhibited (NOS‐I: 10mM L‐NAME), A‐I (5mM BEC + 5mM nor‐NOHA), and L‐arg supplemented (L‐arg: 10mM L‐arg). VD was induced by using a water‐perfused suit to increase core temperature 1.0°C. Red cell flux was measured by laser‐Doppler over each site. Cutaneous vascular conductance was calculated (CVC=flux/MAP) and normalized to maximal CVC (28mM SNP). During heating %CVC max was not different between the groups (HTN: 43±6 vs. AMN: 48±3%CVC max , p>0.05), but maximal CVC was attenuated in HTN subjects (1.47±0.19 vs. 1.83±0.20 flux/mmHg, p=0.01). CVC was higher with NOS‐I in HTN subjects (HTN: 34±5 vs. AMN: 20±5%CVC max , p<0.05). L‐arg did not effect CVC in either group (HTN: 49±5 vs. AMN: 54±5%CVC max , p>0.05), but A‐I augmented CVC only in HTN (HTN: 68±5 vs. AMN: 48±5%CVC max , p<0.05). VD is attenuated with HTN due to decreased NO and can be augmented with arginase inhibition but not L‐arg supplementation.