28 Neurohormonal Regulation in Patients With Neurogenic Orthostatic Hypotension Due to Various Etiologies of Autonomic Neuropathy

Abstract

BackgroundControl of blood pressure involves a complex interaction of hormonal, neurologic, and cardiovascular reflexes. Leptin interacts with other neurotransmitters to regulate sympathetic cardiovascular function. Brain natriuretic peptide (BNP) has diverse physiologic effects, including vasodilatation and natriuresis, and suppresses the renin-aldosterone axis as well as secretion of endothelin-1 and norepinephrine. The exact mechanisms of control are unclear. We evaluated whether these pathways are disrupted in 26 male patients with autonomic dysfunction (AN) and orthostatic hypotension (NOH) due to various etiologies (mean decrease of systolic/diastolic blood pressure (SBP/DBP) = -30 ± 7/-13 ± 3 mm Hg with lack of an adequate tachycardic response to bedside tilt) (mean age of males = 69 ± 2 yrs).MethodsFasting plasma levels of leptin, BNP, and hemodynamic [(changes in blood pressure (SBP/DBP), heartrate (HR)] responses to bedside tilt were evaluated in 7 patients with NOH due to diabetes mellitus (DM) [RR expiratory: inspiratory ratio = 1.03 ± .01; QTC = 435 ± 8 mm; BMI = 29.5 ± 3.1 kg/m2], and 19 NOH due to other etiologies (10 = primary autonomic failure: 2 = Parkinson's disease: 5 = autoimmune: 2 = other) [RR = 1.05 ± .01; QTC = 421 ± 5 mm; BMI = 28 ± 1 kg/m2]. The responses were compared to 10 subjects with DM without NOH [RR = 1.10 ± 0.02; QTC = 424 ± 3 mm; BMI = 28.4 ± 1.8 kg/m2], and 9 aged-matched control subjects [RR = 1.14 ± 0.03; QTC = 405 ± 2 mm; BMI = 28.4 ± 1.4 kg/m2].ResultsLeptin levels correlated with BMI (r = .6, p<.01). Both leptin and BNP levels were higher in NOH (13.6 ± 1.7 ng/mL; 130.9 ± 29.6 pg/mL) than in subjects without NOH (7.8 ± 1.0 ng/mL; 69.2 ± 15.5 pg/mL) (p<.001), despite a lack of differences of body composition. The higher leptin and BNP levels of NOH patients correlated with more abnormal hemodynamics and autonomic function (r = .9; p<.001).ConclusionOur data demonstrate that neurohormonal levels are abnormal in patients with orthostatic hypotension due to autonomic neuropathy. This suggests that neuropeptides may play an important role in the maintenance of normal homeostasis.