Histamine induced pulmonary vasodilatation in the rat: site of action and changes in chronic hypoxia.
Histamine constricts postcapillary lung vessels and also causes dilatation, site unknown. In chronically hypoxic rats, pulmonary arterioles are muscularized and histamine-containing mast cells increase. We wanted to determine a) whether vasoreactivity to histamine changes in chronic hypoxia; b) whether dilatation is due to H2 receptors; and c) which vessels dilate. We perfused isolated lungs of normal (C) and chronically hypoxic (CH) rats. Histamine was tested during hypoxic vasoconstriction. To examine effects on arteries alone, we raised alveolar (inflation) pressure above outflow pressure; during inflation, pressure/flow (P/Q) lines were measured during normoxia, and hypoxia, and after histamine during continued hypoxia. Dose-related dilatation was seen, which was abolished by cimetidine and enhanced in CH rats. A mast cell-discharging agent, but not exogenous histamine, caused constriction, which was abolished by chlorpheniramine. P/Q lines differed in C and CH rats in a manner which suggests that hypoxia constricts larger "extra-alveolar" vessels in C rats, but mainly muscularized arterioles exposed to alveolar pressure in CH rats. Histamine restored the P/Q line to nearly its normoxic position; it therefore dilated those vessels which constrict in hypoxia in each rat group. It is concluded that histamine has a strong H2 dilator effect, enhanced in chronic hypoxia, which might be an important attenuating factor in hypoxic pulmonary hypertension.
Russell
P C
PC
Dept of Medicine, Royal Hallamshire Hospital, Sheffield, UK.
Wright
C E
CE
Barer
G R
GR
Howard
P
P
D000818:Animals; D002908:Chronic Disease; D002927:Cimetidine / Q000494:pharmacology; D006632:Histamine / Q000502:physiology*; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008168:Lung / Q000098:blood supply*; D008297:Male; D010477:Perfusion; D011669:Pulmonary Wedge Pressure; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000502:physiology; D014664:Vasodilation / Q000502:physiology*; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D003189:p-Methoxy-N-methylphenethylamine; D002927:Cimetidine; D006632:Histamine