A novel mechanism of bradycardia and the character of acetylcholine in the heart.

UNLABELLED: At first the aim of our study was to observe the simultaneous responses of two hearts after intraarterial (into a. femoralis) adrenaline administration, in the rat with its own heart and a transplanted one--hence non-innervated. After these, some next experiments were performed: in some rats the His bundle of the heterotopically transplanted heart was damaged before transplantation. In all experiments the heart rate was observed on ECG and simultaneously, the arterial blood pressure was recorded from femoral artery in Vetbutal-anaesthetized rats. RESULTS: 1) both the heterotopically transplanted, non-innervated heart and the animal's own heart reacted to adrenaline administeration by producing bradycardia, 2) the heterotopically transplanted heart with the damaged His bundle--hence with a ventricular block reacted to adrenaline administration by raising the heart rate, whereas at the same time and in the same animal its own heart reacted by producing bradycardia. CONCLUSIONS: 1) the cause of bradycardia after adrenaline administration does not lie in the reflex from the arcus aortae, since we observed bradycardia after adrenaline administration also in the transplanted, non-innervated heart; therefore the baroreceptor reflex is not the cause of bradycardia after adrenaline administration; 2) bradycardia after adrenaline occurs in both the proper heart and the transplanted, non-innervated one, as a result of an interaction between two cholinergic centres which must be situated above and below the point of the His bundle interruption. The role of acetylcholine in the heart results from the interaction between these two centres.

Interaction between the central histaminergic and the muscarinic cholinergic systems.

Histamine (HA) was given intracerebroventricularly (icv) to rats anaesthetized with pentobarbital. During the first minute after administration, HA alone elicited a small fall in blood pressure (BP) and a decrease in heart rate (HR), followed by a distinct increase in those parameters. Pretreatment with naloxone (Nx) in a dose of 0.1 microgram icv significantly decreased the rise in BP and augmented the increase in HR. When the rats were premedicated with atropine methyl bromide (ATMB), 15 min before histamine, higher doses of ATMB (100 micrograms icv or 25 micrograms ip) significantly inhibited the histamine induced BP rise. However, a very small dose (0.1 microgram) of ATMB stimulated the hypertensive response, but only after its peripheral and not central application. These changes were significantly reversed by icv pretreatment with Nx. HA-induced changes in HR, in contrast to BP, were not significantly modified by ATMB.

Antagonistic effect of naloxone on the hypertensive response of intraventricularly administered histamine.

Intracerebroventricular (i.c.v.) injections of histamine (HA) to Vetbutal-anaesthetized rats elicited a biphasic pressure response: a fall of blood pressure (BP) in the first minute, followed by a rise in BP. The heart rate (HR) response was also biphasic: bradycardia in the first minute, followed by tachycardia. The H1-receptor agonist 2-pyridylethylamine (PEA) increased the fall in BP in the first minute in comparison with the HA group, and then elicited a rise in BP that was, however, much lower than that produced by HA. Throughout the experiment PEA produced essentially only a bradycardia. The H2-receptor agonist dimaprit elicited a single-phase pressor response, i.e. a rise in BP and did not elicit tachycardia. Intraventricular pretreatment of rats with naloxone greatly reduced the initial response (phase 1) in the first minute in HA groups by 77-83% and PEA groups by 83-100%. Naloxone given in small doses also reduced the fall in HR by 71-100% in those groups. The experimental results permit a conclusion that the phase 1 response, i.e. the fall in BP, results from excitation of H1-receptors. Thus we may propose that H1-receptors are involved in the action of naloxone. Naloxone in a dose of 0.1 microgram inhibited the hypertensive responses of HA after 25-30 min. The reduction reached 71%. Naloxone reduced the small rise in BP induced by PEA (10 micrograms) but totally blocked the rise in BP induced by dimaprit (50 micrograms). This blockade indicates that the central opioid system may transmit the total stimulating response (rise in BP) of H2 receptors induced by dimaprit. Participation of central opioid receptors in HA-stimulated responses has already been demonstrated in corticosterone secretion.