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Central antidysrhythmic action of substance P in rabbits

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The effect of substance P (SP) and a neurokinin 1 (NK1) receptor antagonist, SR 140 333, infused in the vertebral artery or directly into the fourth ventricle was examined in rabbits subject to spontaneously occurring cardiac dysrhythmias. These experiments were conducted in order to see if SP, already known to increase the baroreflex, could interfere in this cardiac pathology. The results showed that the intravertebral infusion of SP did not change the heart beat pattern, within the limits of the doses used (0.7×10-4 to 3.7×10-9 M). Conversely the same dose of SP, injected into the fourth ventricle, induced a total block of the pathological heart beat pattern. This antidysrhythmic effect is blocked dose dependently by a specific NK1 receptor antagonist, SR 140 333. The extrasystoles could also be abolished by an electric stimulation of aortic nerves or naturally occurring increase of blood pressure. These results suggest that SP may be implied as a neurotransmitter in the baroceptive aortic afferents and demonstrates that it is able to normalize the pathologic heart beat pattern by acting on the baroreflex at the medullar level.


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