HISTAMINE-INDUCED PULMONARY VASODILATATION IN THE RAT - SITE OF ACTION AND CHANGES IN CHRONIC HYPOXIA

Histamine constricts postcapillary lung vessels and also causes dilata tion, site unknown. In chronically hypoxic rats, pulmonary arterioles are muscularized and histamine-containing mast cells increase. We want ed to determine a) whether vasoreactivity to histamine changes in chro nic hypoxia; b) whether dilatation is due to H2 receptors; and c) whic h vessels dilate. We perfused isolated lungs of normal (C) and chronic ally hypoxic (CH) rats. Histamine was tested during hypoxic vasoconstr iction. To examine effects on arteries alone, we raised alveolar (infl ation) pressure above outflow pressure; during inflation, pressure/flo w (P/Q) lines were measured during normoxia, and hypoxia, and after hi stamine during continued hypoxia. Dose-related dilatation was seen, wh ich was abolished by cimetidine and enhanced in CH rats. A mast cell-d ischarging agent, but not exogenous histamine, caused constriction, wh ich 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 expo sed to alveolar pressure in CH rats. Histamine restored the P/Q line t o nearly its normoxic position; it therefore dilated those vessels whi ch constrict in hypoxia in each rat group. It is concluded that histam ine has a strong H2 dilator effect, enhanced in chronic hypoxia, which might be an important attenuating factor in hypoxic pulmonary hyperte nsion.