Systemic functional and structural microvascular alterations in patients with resistant arterial hypertension versus non resistant hypertension

Background Systemic arterial hypertension (SAH) is a prevalent global condition associated with significant microvascular dysfunction. In some individuals, SAH progresses to resistant arterial hypertension (RAH), which carries a poorer prognosis than non-resistant arterial hypertension (NRAH). Purpose This study aimed to evaluate systemic microvascular function in patients with RAH, comparing them to individuals with NRAH and healthy controls (CTL). Methods The study involved 52 patients with RAH (mean age 57.8±7.3 years, 50% men), 35 patients with NRAH (mean age 54±9.4 years, 46% men), and 22 CTL individuals (mean age 56.2±7.3 years, 50% men). Individuals with diabetes were excluded. Microvascular function was assessed in the forearm skin using a laser speckle contrast imaging system. Microvascular blood flow was measured in arbitrary perfusion units (APU) and normalized by mean arterial pressure to calculate cutaneous vascular conductance (CVC, APU/mmHg). Endothelium-dependent vasodilation was evaluated via iontophoresis of acetylcholine (ACh), while endothelium-independent vasodilation was assessed using sodium nitroprusside (SNP), both applied through increasing microcurrents (dose-response curves of 30-180 μA). Post-occlusive reactive hyperemia (PORH) was measured following a 3-minute brachial artery occlusion, with pre- and post-occlusion values recorded. Results There were no significant differences between the groups in terms of age and sex. The areas under the curves (AUCs) for vasodilation induced by ACh were 66±8, 76±8, and 88±9 APU/s for RAH, NRAH, and CTL groups, respectively (Figure 1, P<0.0001). Similarly, the AUCs for SNP-induced vasodilation were 55±7, 62±6, and 70±6 APU/s in the respective groups (Figure 1, P<0.0001). Peak CVC values during PORH were 0.6±0.2, 0.7±0.2, and 0.9±0.2 APU/mmHg for RAH, NRAH, and CTL groups, respectively (Figure 2, P<0.0001). The delta values (peak minus baseline) during PORH were 0.3±0.1, 0.4±0.2, and 0.5±0.2 APU/mmHg for the same groups (Figure 2, P<0.0001). Conclusions Patients with RAH exhibited significantly greater impairments in both endothelium-dependent (ACh and PORH) and endothelium-independent (SNP) vasodilation compared to those with NRAH. These findings indicate that the progression from NRAH to RAH involves both functional (endothelial dysfunction) and structural (arteriolar remodeling) microvascular changes. The observed alterations contribute to increased vascular resistance and reduced vasodilatory capacity in RAH, highlighting the progressive nature of microvascular dysfunction in resistant hypertension. This study underscores the critical role of endothelial dysfunction and microvascular remodeling in the persistence and severity of RAH, suggesting their key involvement in its pathophysiology.