Ind.

Pharmaceuticals Inc., New York,Jy of oxymorphone and Siquil-

esthesia. Acta Anaesth. Scandinav., 11:

d and tissue levels of ether, chlorofonn,106, 1962.eralAnaesthetic Combinations for theiro the Punjab Agricultural University,

.,31: 316-318, 1959.nical Laboratory Methods and Diagno-

latile anaesthetic agent. Vet. Rec., 69:

esia on sheep. Am. J. Very. Res. 29:

Rec., 72: 617-619, 1960.e anaesthesia in horses, effect on blood1968., H. Popper and S. Samdes. FulminantJ. Med., 279 : 798-801, 1968.d chloroform anaesthesia on the equine

nd the evaluation of premedication.

MECHANISM OF STIMULANT EFFECT OF ACETYLCHOLI E IN ISOLATEDFROG HEART

A. W. BHAGWAT, S. S. RAO AND S. S. GUPTA

Department of Pharmacology, Gandhi Medical College, Bhopal

Summary: The mechanism of stimulant effect of acetylcholine has been investigated in atropinised iso-lated frog heart. The effect is reproducible and is not blocked by hexamethonium but is blocked bydichloroisoprenaline, It persists after reserpine treatment and is increased after noradrenaline injectionin such hearts. The mechanism of this effect thus appears to be a dual one, being partly mediatedthrough the release of noradrenaline.

hexamethonium dichloroisoprenaline nicotineKey Words: acetylcholine atropinecardiac stimulant effect

u TRODUCTIO

Isolated rabbit auricles brought to a standstill by quinidine, start contracting againwhenexposed to small concentrations of acetylcholine (2).. Similarly, in atropinised frogheart, acetylcholine produces tachycardia which is blocked 'by ganglion blocking agents (3,6).Thecardiac stimulant effect of acetylcholine in atropinised preparations has been attributedtosympathetic ganglionic stimulation or a direct release of noradrenaline from the sympatheticnerveendings (5). However, although the para sympathetic ganglia are known to exist in thefrogheart, the presence of sympathetic ganglia or similar tissue is uncertain (4). In the presentpaper, the mechanism of the stimulant effect of acetylcholine has been studied in frogheart.

MATERIALS A D METHODS

Isolated frog heart was set up according to the technique of Bulbring (1) and wasperfusedwith frog Ringer solution. The contractions were recorded with Starling heart lever.Thedrugs used were: acetylcholine ( 1x 10":7 to \ I'x '10-5g); atropine sulphate (1X 10-6 g);nicotine(5X 10-6 g) and reserpine (0.5 mg/100 g im for 2 days).

RESULTS AND DISCUSSION

Acetylcholine alone caused cardiac inhibition in all the 12 preparations tested. Afteratropine perfusiou acetylcholine caused cardiac stimulation (Fig. 1) in 7 preparations whilein the remaining 5 preparations cardiac stimulation was not produced even after increasingtheconcentrations of atropine and acetylcholine. The cardiac stimulant effect was reprodu-

160 Bhagwat et al.

. .AA AAAAA" A A ;"·A·

M_ H~ o~

..Fig. 1: Effect of acetylcholine (A at dots) (I) before, (ll) after atropine perfusion (At 1 x 10-6 g), (lIl)after atrop

and hexamethonium perfusion (H 1 x 10-6 g) and (IV) after DCI perfusion (D 1 x 10-6 g). Atrop-perfusion continued during IV.

Fig. 2 : Effect of acetylcholine ·..(Adots) and nicotine (N at din perfused heart of frogtted with reserpine (0.5100 g im for 2 days).atropine perfusion (1xlO-IUpper record shows Ieffects before the administion of noradrenalinelower record shows Iincrease in cardiac stimuleffect of acetylcholine aflprior administrationnoradrenaline (NA at do

olume 16umber 2

cible after repeateperfusion but wasreserpine the cardhearts could beeffect of nicotineeffect of acety1cb

The experilpartly mediatedganglion like stDof acetylcholinereserpine treatinvolved in thii

1. Burn, J.H.2. Briscoe, S.3. Barlow, E.

phia & LOll

4. Evans, C.L.S. Goodman,

New York,6. Heymans, (

lume16umba 2

ible after repeated administration of acetylcholine and was not blocked by hexamethoniumrfusionbut was blocked by DCI in all the 7 preparations (Fig. 1). In hearts treated with.rpine the cardiac stimulant effect of acetylcholine though less than in non-reserpinisedrtscould be elicited in all the preparations (3 experiments) tested. The cardiac stimulant

effectof nicotine was reduced or absent in these preparations. In these hearts the stimulantdT~ctof acetylcholine increased after prior treatment with noradrenaline (Fig. 2).

Cardiac Stimulant Effect of Acetylcholine 161

A •. A .0-+

The experiments indicate that the stimulant effect of acetylcholine in atropinised heart isJrtlymediated through the release of noradrenaline and could not be due to stimulation ofpnglionlike structure. Further, the absence of tachyphylaxis after repeated administrationfacetylcholine in atropinised hearts and the persistence of small but significant effect anareserpinetreatment suggest that the release of noradrenaline may not be the only mechanismml'Olvedin this effect.

Fig. 2 : Effect of .acetylcholine '. (A atdots) and nicotine (N at' dots)In perfused heart of frog trea-ted with reserpine (0.5 mgf100 g. im for .2 days). Atatropine perfusion (1x10-a g)Upper record shows theeffects before the administra_tion of noradrenaline andlower record shows theIncrease III cardiac stimulanteffect of acetylcholine afterprior administration ofnoradrenaline (NA at dots).

REFERENCES

perfusion(At.1 x 10-6 g), (III)after atropineDCI perfusion (D 1 x 10-6 g). Atropine

•I. Burn,J.H. Practical Pharmacology. Blackwell Scientific Publications. Oxford, 1952, P. 30.~.Briscoe,S. and J.H. Burn. Quinidine and acetylcholine. Br. J. Pharmac., 9: 42-45, 1954.J. Barlow, E. Cholinergic agents: In A Mannual of Pharmacology. ed. Sollmann, T. W.B. Saunders Co. Philadel-

phia & London, 1957, P.415.4. Evans,C.L. and H. Hartridge. Principles of Human Physiology, J. & A. Churchill Ltd. London 1956, P. 556.5. Goodman, L.S. and A. Gilman, The Pharmacological Basis of Therapeutics. The MacMillan Company:

New York, 1970, P. 468 .. Heyrnans,C. and C. Bennati. Acetylcholine. Arch. Int.Pharmacodyn. Ther., 79: 486-489,1949.