Involvement of H1 and H2 receptors and soluble guanylate cyclase in histamine-induced relaxation of rat mesenteric collecting lymphatics

Microcirculation. 2014 Oct;21(7):593-605. doi: 10.1111/micc.12138.


Objective: This study investigated the roles of the H1 and H2 histamine receptors, NO synthase, and sGC cyclase in histamine-induced modulation of rat mesenteric collecting lymphatic pumping.

Methods: Isolated rat mesenteric collecting lymphatics were treated with 1- to 100-μM histamine. Histamine receptors were blocked with either the H1 antagonist mepyramine or the H2 antagonist cimetidine. The role of NO/sGC signaling was tested using the arginine analog L-NAME, the sGC inhibitor ODQ, and SNP as a positive control.

Results: Histamine applied at 100 μM decreased tone and CF of isolated rat mesenteric collecting lymphatics. Pharmacologic blockade of either H1 or H2 histamine receptors significantly inhibited the response to histamine. Pretreatment with ODQ, but not L-NAME, completely inhibited the histamine-induced decrease in tone. ODQ pretreatment also significantly inhibited SNP-induced lymphatic relaxation.

Conclusions: H1 and H2 histamine receptors are both involved in histamine-induced relaxation of rat mesenteric collecting lymphatics. NO synthesis does not appear to contribute to the histamine-induced response. However, sGC is critical for the histamine-induced decrease in tone and contributes to the drop in CF.

Keywords: endothelium; lymph flow; lymphatic pump; signal transduction.

Publication types

  • Research Support, N.I.H., Extramural
  • Video-Audio Media

MeSH terms

  • Animals
  • Cimetidine / pharmacology
  • Endothelium, Lymphatic / drug effects
  • Endothelium, Lymphatic / physiology*
  • Guanylate Cyclase / antagonists & inhibitors
  • Guanylate Cyclase / physiology
  • Histamine H1 Antagonists / pharmacology
  • Histamine H2 Antagonists / pharmacology
  • Lymphatic Vessels / drug effects
  • Lymphatic Vessels / physiology*
  • Male
  • Mesentery
  • Muscle Relaxation / drug effects
  • Muscle, Smooth / drug effects
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide / physiology*
  • Nitric Oxide Donors / pharmacology
  • Nitroprusside
  • Oxadiazoles / pharmacology
  • Pyrilamine / pharmacology
  • Quinoxalines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Cytoplasmic and Nuclear / antagonists & inhibitors
  • Receptors, Cytoplasmic and Nuclear / physiology
  • Receptors, Histamine H1 / physiology*
  • Receptors, Histamine H2 / physiology*
  • Soluble Guanylyl Cyclase


  • 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one
  • Histamine H1 Antagonists
  • Histamine H2 Antagonists
  • Nitric Oxide Donors
  • Oxadiazoles
  • Quinoxalines
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Histamine H1
  • Receptors, Histamine H2
  • Nitroprusside
  • Nitric Oxide
  • Cimetidine
  • Guanylate Cyclase
  • Soluble Guanylyl Cyclase
  • Pyrilamine
  • NG-Nitroarginine Methyl Ester