title: Nitric oxide and regulation of heart rate in patients with postural tachycardia syndrome and healthy subjects.
abstract: The objective is to study the role of nitric oxide (NO) on cardiovascular regulation in healthy subjects and postural tachycardia syndrome (POTS) patients. Reduced neuronal NO function, which could contribute to a hyperadrenergic state, and increased NO-induced vasodilation, which could contribute to orthostatic intolerance, have been reported in POTS. In protocol 1, 13 healthy volunteers (33 ± 3 years) underwent autonomic blockade with trimethaphan and were administered equipressor doses of Nω-monomethyl-L-arginine (L-NMMA, a NO synthase inhibitor) and phenylephrine to determine the direct chronotropic effects of NO (independent of baroreflex modulation). In protocol 2, we compared the effects of L-NMMA in 9 POTS patients (31 ± 3 years) and 14 healthy (32 ± 2 years) volunteers, during autonomic blockade. During autonomic blockade, L-NMMA and phenylephrine produced similar increases in systolic blood pressure (27 ± 2 versus 27 ± 3 mm Hg). Phenylephrine produced only minimal heart rate changes, whereas L-NMMA produced a modest, but significant, bradycardia (-0.8 ± 0.4 versus -4.8 ± 1.2 bpm; P=0.011). There were no differences between POTS and healthy volunteers in the systolic blood pressure increase (22 ± 2 and 28 ± 5 mm Hg) or heart rate decrease (-6 ± 2 and -4 ± 1 bpm for POTS and controls, respectively) produced by L-NMMA. In the absence of baroreflex buffering, inhibition of endogenous NO synthesis results in a significant bradycardia, reflecting direct tonic modulation of heart rate by NO in healthy individuals. We found no evidence of a primary alteration in NO function in POTS. If NO dysfunction plays a role in POTS, it is through its interaction with the autonomic nervous system.
authors.affiliation: Division of Clinical Pharmacology, Vanderbilt University, Nashville, TN, USA.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Gamboa
authors.forename: Luis E
authors.initials: LE
authors.lastname: Okamoto
authors.forename: Satish R
authors.initials: SR
authors.lastname: Raj
authors.forename: André
authors.initials: A
authors.lastname: Diedrich
authors.forename: Cyndya A
authors.initials: CA
authors.lastname: Shibao
authors.forename: David
authors.initials: D
authors.lastname: Robertson
authors.forename: Italo
authors.initials: I
authors.lastname: Biaggioni
mesh_terms: D000328:Adult; D001341:Autonomic Nervous System / Q000187:drug effects / Q000503:physiopathology*; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010656:Phenylephrine / Q000494:pharmacology; D054972:Postural Orthostatic Tachycardia Syndrome / Q000503:physiopathology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D010656:Phenylephrine; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase