title: Endogenous histamine stimulates ischemically sensitive abdominal visceral afferents through H1 receptors.
abstract: Abdominal ischemia stimulates sympathetic visceral afferents to reflexly activate the cardiovascular system. We have shown previously that topical application of histamine (HA) to the gastric wall causes reflex cardiovascular responses and have documented increased histamine concentrations in intestinal lymph and portal venous plasma during brief abdominal ischemia. In the present study, we hypothesized that histamine produced during ischemia activates ischemically sensitive C-fiber afferents by stimulation of H1 receptors. Nerve activity of single-unit abdominal visceral C-fiber afferents was recorded from the right thoracic sympathetic chain of anesthetized cats. Injection of histamine (25 micrograms/kg ia) significantly increased activity of nine ischemically sensitive C fibers from 0.09 +/- 0.06 to 1.11 +/- 0.20 imp/s. An H1-receptor agonist, 2-(3-chlorophenyl)histamine (250 micrograms/kg ia), also increased activity of these afferents from 0.11 +/- 0.04 to 0.64 +/- 0.18 imp/s (P < 0.05). Furthermore, an H1-receptor antagonist (pyrilamine, 0.2 mg/kg i.v.) significantly attenuated the increased activity in 11 other C fibers from 0.91 +/- 0.16 to 0.35 +/- 0.06 imp/s ischemia vs. pyrilamine + ischemia) and eliminated the response of 9 separate ischemically sensitive afferents to histamine. Conversely, both the H2-receptor agonist dimaprit (500 micrograms/kg ia) and the H3-receptor.agonist (R)-alpha-methylhistamine (250 micrograms/kg ia) did not significantly alter the activity of these nine afferents. In nine separate cats treated with indomethacin (5 mg/kg i.v.), pyrilamine (0.2 mg/kg i.v.) further significantly attenuated the increased activity in seven of nine C fibers during ischemia, and indomethacin (5 mg/kg i.v.) attenuated the response of eight other afferents to histamine. These data suggest that during mesenteric ischemia endogenous histamine contributes to the activation of afferents through direct stimulation of histamine H1 receptors and that histamine's stimulating effect on these afferents is dependent partially on production of prostaglandins.
authors.affiliation: Department of Internal Medicine and Human Physiology, University of California, Davis 95616, USA.
authors.forename: L W
authors.initials: LW
authors.lastname: Fu
authors.forename: H L
authors.initials: HL
authors.lastname: Pan
authors.forename: J C
authors.initials: JC
authors.lastname: Longhurst
mesh_terms: D000005:Abdomen / Q000098:blood supply*; D000344:Afferent Pathways / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D000818:Animals; D001652:Bile Ducts / Q000098:blood supply; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D002744:Chlorpheniramine / Q000494:pharmacology; D017259:Dimaprit / Q000494:pharmacology; D004386:Duodenum / Q000098:blood supply; D005260:Female; D005704:Gallbladder / Q000098:blood supply; D006632:Histamine / Q000494:pharmacology* / Q000502:physiology; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D007511:Ischemia / Q000503:physiopathology*; D008297:Male; D008761:Methylhistamines / Q000494:pharmacology; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology; D009431:Neural Conduction / Q000187:drug effects; D010179:Pancreas / Q000098:blood supply; D011738:Pyrilamine / Q000494:pharmacology; D011969:Receptors, Histamine H1 / Q000187:drug effects / Q000502:physiology*
chemical_list: D006634:Histamine H1 Antagonists; D008761:Methylhistamines; D011969:Receptors, Histamine H1; D002744:Chlorpheniramine; C069357:alpha-methylhistamine; D006632:Histamine; D011738:Pyrilamine; D007213:Indomethacin; D017259:Dimaprit