Background: Sustained hypotension in end-stage renal disease patients is characterized, despite an overactivation of the sympathetic and renin-angiotensin systems, by decreased vascular resistance and a blunted vascular response to pressor stimuli. An increased production of one or more vasodilator substances might play a role in the reduced vascular resistance and response to pressor stimuli in these patients. We evaluated the possible role of an increased production of nitric oxide and/or adrenomedullin (ADM) in the pathophysiology of chronic hypotension in hemodialysis (HD) patients.
Methods: Three groups of hypotensive (N = 9), normotensive (N = 10), and hypertensive (N = 9) HD patients were included in the study. Plasma renin activity (PRA) and plasma levels of catecholamines, ADM, nitrite/nitrate (an estimator of nitric oxide production), tumor necrosis factor (TNF), and interleukin-1beta (IL-1beta) were measured. Plasma volume and left ventricular ejection fraction (LVEF) were also evaluated.
Results: Plasma levels of nitrite/nitrate and ADM were elevated in HD patients with respect to the reference values in normal subjects. Plasma ADM levels, but not nitrite/nitrate levels, were higher in hypotensive (368.1 +/- 25.4 pg/mL) than normotensive (225 +/- 9.9 pg/mL) and hypertensive HD patients (278.2 +/- 15.5 pg/mL, P < 0.01). When considering hypotensive and normotensive patients together, the mean blood pressure inversely correlated with time on HD (r = -0. 53, P < 0.05) and plasma ADM levels (r = -0.78, P < 0.01).
Conclusions: Plasma ADM and nitrite/nitrate levels are increased in HD patients, but only ADM levels were higher in hypotensive than in normotensive and hypertensive HD patients. The higher plasma levels of this peptide in hypotensive patients and its inverse correlation with mean arterial pressure suggest that ADM may be involved in the pathophysiology of chronic hypotension in HD patients.