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 ACh dose-response protocols, was normalized to CVC (flux MAP-1 ) and a percentage of maximal vasodilation (%CVCmax ). RESULTS: Compared to normotensives, ACh-mediated vasodilation was attenuated in the hypertensive (P<.001), but not in medicated subjects (P=.83). NOS inhibition attenuated ACh-mediated vasodilation in normotensives compared to hypertensive (P<.001) and medicated (P<.001) subjects. With iNOS inhibition, there was no difference in ACh-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.