Role of Nitric Oxide, Endothelin-1, and Inflammatory Cytokines in Blood Pressure Regulation in Hemodialysis Patients

Background: Altered regulation of blood pressure (BP) in hemodialysis patients is associated with increased morbidity and mortality. Regulation of BP is dependent in part on such vasoactive agents as nitric oxide (NO) and endothelin-1 (ET-1). Cytokine-mediated NO synthase activation during dialysis previously has been reported. The purpose of this study is to investigate the relationship between cytokine-mediated activation of the NO and ET-1 systems and BP regulation in hemodialysis patients.

Methods: Nine patients with chronic hypotension (predialysis systolic BP < 110 mm Hg, duration > 1 month), nine patients with hypertension (predialysis systolic BP > or = 180 mm Hg), and nine age- and sex-matched normotensive controls were enrolled.

Results: Predialysis NO end product levels in the hypotensive group were greater than in controls (17.63 +/- 5.9 versus 11.06 +/- 2.12 microm/mL; P = 0.01), whereas the hypertensive group showed lower levels (4.76 +/- 2.33 microm/mL; P < 0.01). The hypotensive group had low postdialysis levels (3.45 +/- 1.11 microm/mL; P = 0.01). Predialysis ET-1 levels in the hypotensive and hypertensive groups were greater in comparison to the normotensive group (7.54 +/- 4.52 and 8.95 +/- 3.52 versus 4.41 +/- 0.6 pg/mL; P < 0.01). Postdialysis endothelin levels increased in both the control and hypertensive groups (P < 0.01). Interleukin-1 and tumor necrosis factor-alpha levels increased postdialysis in all groups, but not significantly.

Conclusion: High levels of NO end products in hypotensive patients and low levels in hypertensive patients suggest a critical influence of NO in BP control. In addition, elevated ET-1 levels in hypertensive patients may contribute to systemic vasoconstriction and may suggest vascular dysfunction in this patient population.