THE USE OF THE RAT RIGHT VENTRICLE STRIP IN STUDIES ON NORADRENERGIC TRANSMISSION

Abstract

The possibility of using contractility studies with the rat right ventricle strip to assess the effects of drugs on all aspects of noradrenergic transmission was examined. The force of the contractile responses to field stimulation at 0.5 and 2, but not 5 Hz, markedly decreased with time. About 55% of the tissues responded directly to (.sbd.)-isoprenaline, 1 .times. 10-6 M (123 tissues from 220 tested) in the absence of other stimuli. In these tissues, the force of the contractile responses remained constant and the rate increased with time. It is essential to provide time controls in studies with rat right ventricle. Under conditions in which the responses to (.sbd.)-isoprenaline, 1 .times. 10-6 M, alone were unaffected, the responses to field stimulation at 5 Hz were inhibited by 66 and 86% by 9 .times. 10-6 M tetrodotoxin and 1 .times. 10-5 M guanethidine, respectively. (.+-.)-Propranolol and timolol (both at 1 .times. 10-6 M), but not phentolamine, 1 .times. 10-6 M, inhibited response to (.sbd.)-isoprenaline, 1 .times. 10-6 M alone and responses to field stimulation at 5 Hz. The responses to field stimulation are largely due to activation of noradrenergic nerves, the released noradrenaline [norepinephrine] acting at postsynaptic .beta.-adrenoreceptors. Although nortriptyline is a potent inhibitor of the neuronal uptake of noradrenaline, at 1 .times. 10-6 M it had no effect on the contractile responses to field stimulation at 5 Hz and inhibited responses to (.sbd.)-isoprenaline, 1 .times. 10-6 M, alone and at a higher concentration (1 .times. 10-5 M) nortriptyline abolished both responses. The rat right ventricle preparation may be useful in examining the effects of drugs on noradrenergic tramsmission in the heart.