Control 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; BMI = 28.5 ± 1.8)].
Methods Fasting 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], 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]. The responses were compared to 10 subjects with DM without NOH [RR = 1.10 ± 0.02; QTC = 424 ± 3 mm], and 9 aged-matched control subjects [RR = 1.14 ± 0.03; QTC = 405 ± 2 mm].
Results Leptin levels correlated with BMI (r = .6, p<.01). Both leptin and BNP levels were higher in NOH with and without DM (13.1 ± 4.2 ng/mL;112.6 ± 40.0 pg/mL and 13.7 ± 1.9 ng/mL; 137.6 ± 38.3 pg/mL) than in DM without NOH and controls (6.8 ± 1.3 ng/mL; 62.6 ± 21.3 pg/mL and 8.6 ± 3.7 ng/mL; 74.3 ± 23.4 pg/mL) (p<.001), despite lack of differences in body composition. The higher leptin and BNP levels of NOH patients correlated with more abnormal hemodynamics (r = .9; p<.001).
Conclusion Our data suggest that the neuropeptides play a role in the regulation of blood pressure in patients with autonomic neuropathy.
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