Bronchial vasodilation by histamine in sheep: characterization of receptor subtype.
Histamine has been shown to mediate features of pulmonary allergic reactions including increased tracheobronchial blood flow. To determine whether the increase in blood flow was due to stimulation of H1- or H2-histamine receptors, we gave histamine base (0.1 micrograms/kg iv) or histamine dihydrochloride as an aerosol (10 breaths of 0.5% "low dose" or 5% "high dose") before and after H1- or H2-receptor antagonists. Blood velocity in the common bronchial branch of the bronchoesophageal artery (Vbr) was continuously measured using a chronically implanted Doppler flow probe. Pretreatment with H2-receptor antagonists cimetidine, ranitidine, or metiamide did not affect the increase in Vbr induced by intravenous histamine [106 +/- 45% (SD)]. Addition of the H1-receptor antagonists diphenhydramine or chlorpheniramine, however, reduced the Vbr response to 16 +/- 22, 21 +/- 28, 23 +/- 23, and 37 +/- 32% of the unblocked responses (P less than 0.05) when intravenous histamine was given at 3, 10, 20, and 30 min, respectively, after the H1 antagonist. At 40, 50, and 60 min the H1-receptor blockade appeared to attenuate, but subsequent continuous infusion of chlorpheniramine (2 mg.kg-1.min-1) then blocked the histamine response for 60 min. Low-dose histamine aerosol did not change mean arterial or pulmonary arterial pressures, cardiac output, or arterial blood gases but increased Vbr transiently from 15.2 +/- 3.4 to 37.6 +/- 8.4 (SE) cm/s. After chlorpheniramine, the Vbr response to histamine, 16.3 +/- 2.2 to 22.6 +/- 3.6 cm/s, was significantly reduced (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Parsons
G H
GH
Department of Medicine, University of California, Davis 95616.
Villablanca
A C
AC
Brock
J M
JM
Howard
R S
RS
Colbert
S R
SR
Nichol
G M
GM
Chung
K F
KF
D000336:Aerosols; D000818:Animals; D001980:Bronchi / Q000098:blood supply* / Q000187:drug effects*; D002927:Cimetidine / Q000494:pharmacology; D004155:Diphenhydramine / Q000494:pharmacology; D006632:Histamine / Q000008:administration & dosage / Q000494:pharmacology*; D007275:Injections, Intravenous; D011969:Receptors, Histamine H1 / Q000187:drug effects / Q000502:physiology; D011970:Receptors, Histamine H2 / Q000187:drug effects / Q000502:physiology; D012756:Sheep; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D000336:Aerosols; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D002927:Cimetidine; D006632:Histamine; D004155:Diphenhydramine