Blood pressure normalization via pharmacotherapy improves cutaneous microvascular function through NO‐dependent and NO‐independent mechanisms

Hypertension is associated with endothelial dysfunction and vascular remodeling. Objective To assess effects of antihypertensive pharmacotherapy on eNOS ‐ and iNOS ‐dependent mechanisms and maximal vasodilator capacity in the cutaneous microvasculature. Methods Intradermal microdialysis fibers were placed in 15 normotensive ( SBP 111±2 mm Hg), 12 unmedicated hypertensive ( SBP 142±2 mm Hg), and 12 medicated hypertensive ( SBP 120±2 mm Hg) subjects. Treatments were control, iNOS ‐inhibited (1400w), and NOS ‐inhibited ( l ‐ NAME ). Red cell flux, measured during local heating (42°C) and AC h dose‐response protocols, was normalized to CVC (flux MAP −1 ) and a percentage of maximal vasodilation (% CVC max ). Results Compared to normotensives, AC h‐mediated vasodilation was attenuated in the hypertensive ( P <.001), but not in medicated subjects ( P =.83). NOS inhibition attenuated AC h‐mediated vasodilation in normotensives compared to hypertensive ( P <.001) and medicated ( P <.001) subjects. With iNOS inhibition, there was no difference in AC h‐mediated vasodilation between groups. Compared to the normotensives, local heat‐induced vasodilation was attenuated in the hypertensives ( P <.001), but iNOS inhibition augmented vasodilation in the hypertensives so this attenuation was abolished ( P =.31). Compared to normotensives, maximal vasodilator capacity was reduced in the hypertensive ( P =.014) and medicated subjects ( P =.004). Conclusions In the cutaneous microvasculature, antihypertensive pharmacotherapy improved endothelial function through NO ‐dependent and NO ‐independent mechanisms, but did not improve maximal vasodilator capacity.