Effects of Repetitive Stimulation by Norepinephrine, Histamine or Potassium Chloride on Contractile Responses of Pulmonary Vascular Smooth Muscle

Abstract

We examined consecutive contractile responses of isolated rabbit pulmonary arteries during repeated exposures to either norepinephrine, histamine or KCl, with washout and relaxation between trials. For each agonist, EC₅₀ values remained constant during consecutive determinations, but the maximum force increased after the first determination. A maximum concentration of norepinephrine or histamine produced a biphasic contraction: the fast phase increased subsequent to the first determination and was retained in a calcium-free medium, while the slow phase was unaltered during consecutive determinations and was absent in a calcium-free medium. We conclude that in the rabbit pulmonary artery: (l)the initial contractile response is a useful control for studies of sensitivity but not of maximum activity; (2) there may be a nonspecific increase in the availability of intracellular calcium after the initial contraction and relaxation, and (3) desensitization or tachyphylaxis to these agonists does not occur.