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 mmHg), 12 unmedicated hypertensive (SBP 142±2 mmHg), and 12 medicated hypertensive (SBP 120±2 mmHg) subjects. Treatments were control, iNOS-inhibited (1400w), and NOS-inhibited (L-NAME). Red cell flux, measured during local heating (42°C) and acetylcholine (ACh) dose-response protocols, was normalized to cutaneous vascular conductance (CVC=flux•MAP−1) and a percentage of maximal vasodilation (%CVCmax).
Results
Compared to normotensives, ACh-mediated vasodilation was attenuated in the hypertensive (p<0.001), but not medicated subjects (p=0.83). NOS inhibition attenuated ACh-mediated vasodilation in normotensives compared to hypertensive (p<0.001) and medicated (p<0.001) 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<0.001), but iNOS inhibition augmented vasodilation in the hypertensives so this attenuation was abolished (p=0.31). Compared to normotensives, maximal vasodilator capacity was reduced in the hypertensive (p=0.014) and medicated subjects (p=0.004).
Conclusion
In the cutaneous microvasculature, antihypertensive pharmacotherapy improved endothelial function through NO-dependent and independent mechanisms, but did not improve maximal vasodilator capacity.