DIFFERENT HISTAMINE ACTIONS IN PROXIMAL AND DISTAL HUMAN CORONARY-ARTERIES INVITRO

Study objective - The aim was to investigate the receptor mechanisms for different histamine actions in proximal and distal human coronary arteries.Design - Postmortem human coronary rings precontracted by 50 mM KC1 were exposed to histamine (10-8 - 10-4) in control and after treatment with 10-5 M pyrilamine (an H1 receptor antagonist), or 10-4 M cimetidine (an H2 receptor antagonist), and/or endothelial removal. Tension changes at the point of maximum relaxation (at 10-5 M in most rings) were obtained.Measurements and results - Endothelium dependent relaxations to histamine were clearly distinguished from endothelium independent relaxations by their transient nature and their inhibition by pyrilamine, but not by cimetidine. While most distal rings (group I, n = 42/58) and only some of the proximal rings (group II, n = 10/83) showed >50% relaxation with histamine, nearly half the proximal rings (group III, n = 40/83) showed only contraction. Signifcant differences were found between group I and III, but not II, in control [-66(SD 15.2)% v +25(20.4)%, p<0.00l] and after pyrilamine treatment [-66(9.2)% v -25(12.0)%, p<0.00l], cimetidine treatment [-30(25.5)% v +42(20.9)%, p<0.001] and endothelial removal [-24(37.1)% v +36(20.2)%, p<0.0l]. However, a combination of cimetidine and endothelial removal resulted in a contraction to histamine which was similar among the three groups.Conclusions - These results suggest that hypercontractility to histamine was found in proximal human coronary arteries, but not in distal ones, probably due to the reduction of both direct and endothelial mediated relaxations rather than to an increase in the contraction itself.