ENDOGENOUS HISTAMINE STIMULATES ISCHEMICALLY SENSITIVE ABDOMINAL VISCERAL AFFERENTS THROUGH H-1 RECEPTORS

Abdominal ischemia stimulates sympathetic visceral afferents to reflex ly activate the cardiovascular system. We have shown previously that t opical application of histamine (HA) to the gastric wall causes reflex cardiovascular responses and have documented increased histamine conc entrations in intestinal lymph and portal venous plasma during brief a bdominal ischemia. In the present study, we hypothesized that histamin e produced during ischemia activates ischemically sensitive C-fiber af ferents by stimulation of H-1 receptors. Nerve activity of single-unit abdominal visceral C-fiber afferents was recorded from the right thor acic sympathetic chain of anesthetized cats. Injection of histamine (2 5 mu g/kg ia) significantly increased activity of nine ischemically se nsitive C fibers from 0.09 +/- 0.06 to 1.11 +/- 0.20 imp/s. An Hi-rece ptor agonist, 2-(3-chlorophenyl)histamine (250 mu g/kg ia), also incre ased activity of these afferents from 0.11 +/- 0.04 to 0.64 +/- 0.18 i mp/s (P < 0.05). Furthermore, an H-1-receptor antagonist (pyrilamine, 0.2 mg/kg iv) significantly attenuated the increased activity in 11 ot her C fibers from 0.91 +/- 0.16 to 0.35 +/- 0.06 imp/s (ischemia vs. p yrilamine f ischemia) and eliminated the response of 9 separate ischem ically sensitive afferents to histamine. Conversely, both the H-2-rece ptor agonist dimaprit (500 mu g/kg ia) and the H-3-receptor agonist (R )-alpha-methylhistamine (250 mu g/kg ia) did not significantly alter t he activity of these nine afferents. In nine separate cats treated wit h indomethacin (5 mg/kg iv), pyrilamine (0.2 mg/kg iv) further signifi cantly attenuated the increased activity in seven of nine C fibers dur ing ischemia, and indomethacin (5 mg/kg iv) attenuated the response of eight other afferents to histamine. These data suggest that during me senteric ischemia endogenous histamine contributes to the activation o f afferents through direct stimulation of histamine H-1 receptors and that histamine's stimulating effect on these afferents is dependent pa rtially on production of prostaglandins.