title: Protamine after heparin produces hypotension resulting from decreased sympathetic outflow secondary to increased nitric oxide in the central nervous system.
abstract: To elucidate whether there are linkages among protamine-induced hypotension, nitric oxide (NO), and sympathetic nerve activity, we administered 3 mg/kg protamine sulfate after 300 U/kg heparin after 20 mg/kg of N(G)-nitro-D-arginine methyl ester (D-NAME) or N(G)-nitro-L-arginine methyl ester (L-NAME) as a pretreatment to baroreceptor-denervated rabbits and compared changes in hemodynamic variables and renal sympathetic nerve activity (RSNA). In the D-NAME group, heart rate (HR), mean arterial blood pressure (MAP), and RSNA significantly decreased to 93.7% +/- 0.7%, 75.0% +/- 5.1% and 65.2% +/- 4.6% (mean +/- SE), respectively. In the L-NAME group, the pretreatment of L-NAME significantly inhibited the depressant effects of protamine on these variables. Because the animals were totally baroreceptor-denervated, decreased RSNA was attributable to the central depressant effect of protamine, and decreased sympathetic outflow could have contributed to the reduction of HR and MAP. The depressant effect of protamine on sympathetic outflow was inhibited by the pretreatment with L-NAME, a NO synthase inhibitor, suggesting that decreased sympathetic outflow secondary to a protamine-induced increase in NO concentration in the central nervous system may contribute to protamine-induced cardiovascular depression.
authors.affiliation: *Department of Anesthesiology, Tokyo Medical University, Shinjuku, Tokyo, Japan; †Department of Anesthesiology, University of Kansas Medical Center, Kansas City, Kansas.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Hamada
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kameyama
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Narita
authors.forename: Kirk T
authors.initials: KT
authors.lastname: Benson
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Goto
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002490:Central Nervous System / Q000378:metabolism*; D003714:Denervation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006493:Heparin / Q000009:adverse effects*; D006494:Heparin Antagonists / Q000009:adverse effects*; D007022:Hypotension / Q000139:chemically induced* / Q000503:physiopathology*; D007668:Kidney / Q000187:drug effects / Q000294:innervation; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D011311:Pressoreceptors / Q000502:physiology; D011479:Protamines / Q000009:adverse effects*; D011817:Rabbits; D013564:Sympathetic Nervous System / Q000503:physiopathology*
chemical_list: D004791:Enzyme Inhibitors; D006494:Heparin Antagonists; D011479:Protamines; D009569:Nitric Oxide; D006493:Heparin; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester