Document Detail


Nitric oxide and regulation of heart rate in patients with postural tachycardia syndrome and healthy subjects.
MedLine Citation:
PMID:  23283362     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Alfredo Gamboa; Luis E Okamoto; Satish R Raj; André Diedrich; Cyndya A Shibao; David Robertson; Italo Biaggioni
Publication Detail:
Type:  Clinical Trial; Journal Article; Research Support, N.I.H., Extramural     Date:  2013-01-02
Journal Detail:
Title:  Hypertension     Volume:  61     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-17     Completed Date:  2013-03-20     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  376-81     Citation Subset:  IM    
Data Bank Information
Bank Name/Acc. No.:
ClinicalTrials.gov/NCT00770484
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MeSH Terms
Descriptor/Qualifier:
Adult
Autonomic Nervous System / drug effects,  physiopathology*
Baroreflex / drug effects,  physiology
Blood Pressure / drug effects,  physiology*
Enzyme Inhibitors / pharmacology
Female
Heart Rate / drug effects,  physiology*
Humans
Male
Nitric Oxide / physiology*
Nitric Oxide Synthase / antagonists & inhibitors
Phenylephrine / pharmacology
Postural Orthostatic Tachycardia Syndrome / physiopathology*
omega-N-Methylarginine / pharmacology
Grant Support
ID/Acronym/Agency:
K23 HL-95905/HL/NHLBI NIH HHS; K23 HL095905/HL/NHLBI NIH HHS; P01 HL056693/HL/NHLBI NIH HHS; P01 HL056693/HL/NHLBI NIH HHS; U54 NS065736/NS/NINDS NIH HHS; UL1 TR000445/TR/NCATS NIH HHS; UL1 TR000445/TR/NCATS NIH HHS
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 1WS297W6MV/Phenylephrine; 27JT06E6GR/omega-N-Methylarginine; 31C4KY9ESH/Nitric Oxide; EC 1.14.13.39/Nitric Oxide Synthase
Comments/Corrections

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