Hemodynamic and microvascular abnormalities in P450 oxidoreductase deficiency: evidence for COX-dependent dysfunction.

OBJECTIVE

Cytochrome P450 oxidoreductase deficiency (PORD) is a rare form of congenital adrenal hyperplasia caused by impaired electron transfer to multiple microsomal enzymes. Hypertension in PORD has been attributed to mineralocorticoid excess; however, experimental evidence suggests that POR may also regulate endothelial vasodilatory pathways. The vascular effects of PORD in humans remain poorly defined. We evaluated blood pressure regulation, microvascular structure, and serum vasoactive mediators in patients with PORD.

DESIGN

Observational, cross-sectional study.

METHODS

Ten patients with genetically confirmed PORD (4 females, 6 males; age range 8-27 years) and 41 age- and sex-matched healthy controls were evaluated. Office and 24-hour ambulatory blood pressure monitoring (ABPM) were performed. Microvascular structure was assessed using nailfold capillaroscopy (NFC). Serum levels of thromboxane B₂ (TXB₂), prostaglandin E₂ (PGE₂), and nitric oxide (NO) were measured.

RESULTS

Hypertension was present in 80% of patients with PORD compared with 7.3% of controls (P < .001). Office and ambulatory systolic and diastolic pressures were significantly higher in PORD. NFC revealed shorter capillary length (P = .001), more frequent crossed capillaries (P < .001), and avascular areas (P = .039). Serum TXB₂ levels were higher in PORD (P = .007), whereas PGE₂ and NO did not differ between groups.

CONCLUSIONS

PORD is associated with an increased prevalence of hypertension, microvascular capillary abnormalities, and elevated TXB₂, consistent with enhanced cyclooxygenase-mediated vasoconstrictor tone and endothelial dysfunction. These findings suggest that cyclooxygenase-dependent mechanisms may contribute to the vascular alterations observed in PORD.