ALVEOLAR, BRONCHIOLAR AND PULMONARY VASCULAR 
RESPONSES OF ISOLATED RAT AND GUINEA PIG LUNGS 
Frederick Sperling,' William L. Marcus" and A-A. 0. Coker* 
Continuously perfused, isolated rat and guinea pig 
lungs, which breathe by negative pressure, and which 
may be injected with single doses of drugs, permit dis- 
tinction between alveolar and bronchiolar effects. This 
distinction is based on the pulmonary vascular differ- 
ences, between the species, in anastomoses between pul- 
monary and bronchial arteries. The differences in re- 
sponse between the pulmonary and the systemic vascu- 
lature may also be distinguished. Barbiturates have been 
shown to be concentrated by the lungs of both species, 
to be retained for long periods of time, and to exert 
profound peripheral inhibitory effects on the capability 
of the lungs to inflate. Differences in the two species in 
response to the barbiturates are small. The two species 
differ in their response to autonomic drugs. Pulmonary 
artery injection in guinea pig lungs appear to reach the 
bronchioles and to affect them. In the rat, the primary 
effect appears to be on the alveoli, and it is doubtful 
that the bronchioles are reached. The pulmonary vas- 
culature of the rat lung does not respond in the same 
manner as does the systemic vasculature. Acetylcholine 
constricts; norepinephrine induces progressively lesser 
constriction with repetitive or increasing doses; isopro- 
terenol dilates. The actions of each of these can be 
blocked by the appropriate blocking agent. All of the 
barbiturate and autonomic effects noted may be rever- 
sible or irreversible, and appear to be dose-related. 
INTRODUCTION*** 
It is now possible in isolated perfused pul- 
monary systems to distinguish alveolar re- 
sponses from those of the tracheobronchiolar 
tree. The tidal volume increases or decreases, 
which may be seen in response to pharmacologi- 
cally active agents, may be due to changes in 
airway patency, alveolar expansibility or both. 
It is now also possible in such systems to 
simultaneously and independently observe 
changes in the pulmonary vascular system. 
Variations in perfusion flow rate reflect vas- 
cular constriction or dilatation. Pulmonary vas- 
• Department of Pharmacology, Howard University College of 
Medicine, Washington, D. C. 
** Oakdale Toxicology Center, University of Iowa, Oakdale, Iowa 
52319. 
Supported in part, by USPHS Grant No. EC-00234. 
cular responses may differ from those of the 
systemic vasculature. 
It can now be shown m vitro and in vivo that 
the pulmonary system has functions other than 
those associated with the exchange of gases 
and other substances between the environment 
and the circulation. Lungs can concentrate many 
circulating substances and retain them for long 
periods of time. Such retained substances, and 
probably others in the circulation as well, may 
have significant peripheral effects on the pul- 
monary system. 
The pulmonary system may be divided into 
three morphologically and physiologically dis- 
tinct parts. The airways are for the most part 
lined internally with a pharmacologically re- 
active and secreting epithelium. They are cov- 
ered, for the most part, with a pharmacologi- 
cally reactive smooth muscle coat. They open 
into the alveoli which are walled by thin parti- 
tions consisting of capillary endothelium, two 
types of scattered epithelial cells, one of which 
secretes the pulmonary surfactant, scattered 
Mast cells in many species, scattered histio- 
cytes, and scattered red and white blood cells. 
There are no smooth muscle fibers. Aside from 
the Mast cells and the surfactant-secreting 
epithelial cells, little pharmacological attention 
has been paid to the other elements and to the 
alveolus as a unit.^ 
The alveoli are separated from each other by 
interalveolar septae through which pass a com- 
plex system of capillaries (Figures 1 & 2) . These 
capillaries arise from the pulmonary artery 
originating from the right ventricle and drain 
into the pulmonary veins entering the left 
atrium. These veins also join, via capillaries and 
anastomoses, with bronchial veins and arteries 
the arteries arising from the aorta. In some 
species, such as the rat, large numbers of atrial 
fibers are found in the walls of the large col- 
243 
