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Post‐Junctional Adrenergic Neurotransmission is Inhibited by Nitric Oxide (NO) in Humans
Author(s) -
Del Pozzi Andrew,
Medow Marvin,
Stewart Julian
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.649.2
Subject(s) - phenylephrine , transcranial doppler , medicine , sodium nitroprusside , vasoconstriction , neurotransmission , anesthesia , middle cerebral artery , heart rate , saline , adrenergic , omega n methylarginine , nitric oxide , hemodynamics , blood pressure , endocrinology , nitric oxide synthase , receptor , ischemia
NO, can modulate adrenergic vasoconstriction by central reduction of sympathetic outflow and by peripheral effects in animal models. We investigated whether NO inhibits post–synaptic α‐1‐adrenergic neurotransmission in humans. To accomplish this we performed intravenous phenylephrine dose‐response experiments under three conditions: during a control saline infusion, after NOS inhibition with L‐N G ‐monomethyl Arginine (L‐NMMA), and following restoration of NO by adding sodium nitroprusside (SNP) to L‐NMMA. We studied 11 healthy controls (21 ±3 yrs) using repeated measures ANOVA. All subjects received at least 0.5, 1.0, and 2.0 µg/kg/min in sequence. Patients were instrumented with an oscillometric BP cuff, EKG, and beat‐to‐beat BP, cardiac output (CO), and total peripheral resistance using a Finometer with ModelFlow software. We measured cerebral blood flow velocity (CBFv) in the middle cerebral artery with transcranial Doppler ultrasound. Saline and L‐NMMA experiments were performed on different days. L‐NMMA increased pre‐phenylephrine MAP by 7% while reducing HR by 8% and increasing CBFv by 13%. The change in MAP, and TPR were significantly increased with L‐NMMA (P < 0.001) and returned to baseline following administration of SNP (P > 0.05) for all levels of the dose‐response. HR and CO were significantly decreased with L‐NMMA (P < 0.001) and was returned to baseline with SNP (P > 0.05) for all levels of the dose‐response. The change in CBFv was unaffected (curves were parallel). We conclude that post‐junctional adrenergic neurotransmission is inhibited by NO in humans. Inhibition could occur by reduction of α‐1‐adrenergic properties or of neurovascular transduction.