From the Department of Physiology, Uniyersity of Lund.

The Sympathetic Vasomotor Innervation of' the Skin of the Dog.

BY

BJORN FOLKOW, JBRGEN FROST, KNUT H B G E R and BORJE UVNAS.

Received 28 September 1948.

In a series of papers BULBRING and BURN (1935, 1936, 1937) investigated the distribution and functional significance of sym- pathetic vasodilator nerves in different animal species. No syni- pathetic vasodilator supply was found to the skin, except to the skin of the ear of the dog. According t o these authors the syni- pathetic vasodilator fibres are of two types, cholinergic and adrenergic. Since BULBRING and BURN were unable to detect a n y dilator action of acetylcholine on cutaneous vessels of the dog they concluded tha t the synipathetic vasodilator fibres to the ear were not cholinergic.

I n a series of papers we argue tha t sympathetic vasodilator fibres generally might be cholinergic (FOLKOW e t al. 1948). Since we (FOLKOW and UVNAS 1948) unlike BULBRING and BURN ob- served a pronounced dilator action of acetylcholine on cutaneous vessels, the following experinients were performed.

Experimental.

The experiments were performed on dogs under nenibutal (30 mg/kg) or combined chloralose (50 mg/kg)-urethane (500 mg/kg) anaesthesia. Observations were made on the cutaneous vessels of the hind limbs and of the ear. Adrenaline, nor-adrenaline and acetylcholine were given intraarterially, dibenamine and ergotamine slowly intravenously. For nerve &mulation n Sherrington electrode and a thyratron stim- ulator delivering 60 impulses per second mere used.l

1 The blood pressure was measured in the brachial artery by a mercury mano- meter. Heparin waB used as an anticoagulant.

196 BJbRX FtOLROW, JBRGEN FROST, KSUT HXGER AND BORJE UVNAS.

Experiments on Hind Limbs.

In four (..\i)eritnents the experitnental arrangement was the same . I \ clrscribed by Fo~rtow and UTSAS (1948). The caval and the coinl,inetl saphenous outflows from both hind limbs were registered separately by two Gaddum recorders. In five other experiments the cwtaneous flow n-as registered in the following wdy. The one femoral artery was ligated just distally to the origin of the saphenous artery. .I Imnrh of the femoral artery just pioxiiiially to this point was i w l a t t d and caniiulated for .‘clo\e arterial injections” to the saphenous 1 asctilar region. The venous outflow from lioth saphenous veins of t h e legs wa4 registered by an electrical drop recorder connected t o an “C)1.diiiatensctir[,i~)fir”. In thcbe tr,icinys the height of the record iiiPawres the intrr\ a1 hetween successive drops.

Rrsztl la.

Experiments were pertornied on 9 dogs. Stimulation of the ab- tioniinal sympathetic chains produced a marked cutaneous vaso- constriction. This constrictor effect was considerably reduced b u t never annulled by the synipatholytic effect of dibenamine or ergotanline, not even if these drugs were given conconiitaritly in huge doses (dibenamine 30 ing and ergotanline 5 nig per kg body \\-eight). The vasoconstrictor effect was never observed to be re- versed to a vasodilator effect under the influence of these drugs.

Intrnarterial injections of adrenaline and of nor-adenaline pro- duced a vasoconstriction of about the same magnitude (see fig. 1). S o vasodilator action was observed by sinall doses of these drugs. The vasoconstrictor effects were reduced but usually not abolished by tlibennruine or ergotamine. Under t h e influence of huge doses of these drugs adrenaline occasionally produced a slight vasodilatation. I n all experiinents acetylcholine proved to have a pronounced vasodilator action on the cutaneous a s well as on the muscular vessels.

The action of adrenaline, nor-adrenaline and acetylcholine on the saphenal outflow is shown in fig. 1. Identical results were ob- tained in all 9 experiments.

Experiments on the Skin of the Ear.

The one common carotid was isolated and all branches were ligated except those supplying the ear. Intraarterial injections were made into the cannulated st,ump of the lingual artery. The vago-sympathetic

THE SYMPATHETIG VASOMOTOR INNERVATION OF THE SKIN. 197

Fig. 1. Dog 6 kg. Chloralose-urethane. Blood pressure 130 mm Hg. Saphenal outflow of right leg. Action of adrenaline, nor-adrenaline and acetylcholine given

intraarterially.

trunk was isolated in the neck and cut a few centimeters above the thorax aperture. In order to exclude reflex vascular responses in the ear due to afferent vagal impulses the vagus was severed just where it emerges from the skull. Care was taken to leave the sympathetic fibres intact. The two marginal veins of the ear were cannulated and the venous outflow registered by an electrical drop recorder connected to an “Ordinatenschreiber” as mentioned above.

Results. Experiments were carried out on 12 dogs. Stimulation of the sympathetic trunk produced a very pro-

nounced vasoconstriction in the ear (see fig. 2 ) . We were not able to block this constrictor effect completely even if huge doses of dibenaniine and ergotamine were given. Adrenaline and nor- adrenaline elicited vasoconstrictions of about equal magnitude. No vasodilatation with small doses was ever observed. The con- strictor action of nor-adrenaline was more or less completely blocked by ergotamine or dibenamine but the constriction was never reversed to a dilatation. Occasionally the constrictor action of adrenaline changed into a slight dilator action under the in- fluence of large doses of dibenamine and ergotamine (see fig. 2). As was the case with the skin of the hind limbs intraarterial in- jection of acetylcholine produced a pronounced vasodilatation in the ear.

The actions of adrenaline, nor-adrenaline and acetylcholine on the skin of the ear are shown in fig. 2 and 3.

198 UJORS E‘PLKOTT. JORGES FROST, KSUT HAXER AND UORJE I;VN;~P.

Fig. 2 . Dog I:! kg. C’1iloralosc.urctlranr. Venous outflow from the marginal reins of the ear registered by “Ordinatenschreiber”.

A. 1-asoconstrictur actiun of stimulation of thc sympathetic trunk in the neck,

B. ‘rhc influencc of dibenamine and ergotamine on t,he vasomotor responses to arid of adrcnalinr. \.asodilator action of acetylcholine.

stimulation of’ the sympathetici;. to adrenaline and to acetylcholine.

Fig. nal

3. Dog 7.6 kg. Xembrital. Hlood pressure 110 mm Hg. Outflow from the margi- veins of the car registered by “Ordinstenschreiber”. Action of acetylcholine,

adrenaline and nor-adrenaline given intraarterially.

Discussion.

BULBRIXG and BVRN (1936) claim the existence of sympathetic vasodilator fibres to the skin of the ear of the dog. Under the in- fluence of ergotamine stimulation of the sympathetic trunk in the

THE SYMPATHETIC VASOMOTOR INNERVATION OF THE SKIN. 199

neck was observed to produce an increase of the volume of the ear. This increase of volume was unaffected by atropine, or by eserine. Purther BULBRING and BURN were unable to demonstrate any dilator action of acetylcholine on cutaneous vessels. Conse- quently they concluded that the supposed sympathetic vasodilator nerves to the skin of the ear were not cholinergic.

Our observations do not agree with those of BULRRIKG and BURN. We have not been able to find any evidence for the existence of sympathetic vasodilators to the skin of the ear of the dog. The vasoconstriction produced by stimulation of the synipathetics in the neck was never reversed to a vasodilatation under the in- fluence of the sympatholytic drugs dibenamine and ergotamine. We are not convinced that the results obtained by the use of the plethysniographic technique of BULBRING and BURN justify the conclusions made by them. Even used in skilled hands this in- direct recording technique has its disadvantages. Further, when covering the ear of the dog the plethysmograph will enclose the muscles of the ear as well. The records will then include the vasomotor reactions in these muscles.

Our observations that the skin of the dog lacks sympathetic vasodilator innervation agrees with our previous observations on the cutaneous sympathetic vasomotor innervation of the cat.

Against the claims of BULBRING and BURN we have observed acetylcholine to have a pronounced dilator action on cutaneous vessels. I n our view acetylcholine is well fitted to be the trans- mitter a t nerve endings of cutaneous vasodilator nerves.

Adrenaline and nor-adrenaline exert a pronounced cutaneous vasoconstriction of about equal magnitude. This observation is in agreement with our claim (POLKOW et al. 1948) that nor- adrenaline might be the transmitter a t vasoconstrictor nerve endings.

Summary.

No evidence was found for the existence of a sympathetic vaso- dilator innervation to the skin of the hind limbs or the ear of the dog.

Nor-adrenaline has a pronounced vasoconstrictor action on cutaneous vessels. The observation agrees with the idea that the

200 BJORN FOLKOW, JCtRGES FROST. E N C T IIZGER AND B6RJE VVNAS.

substance might be the transmitter a t vasoconstrictor nerve endings.

Adrenaline has a pure vasoconstrictor action on cutaneous vessels, even in low concentrations.

Acetylcholine has a pronounced vasodilator action on cutaneous vessels. Thus it cannot be excluded as a possible transmitter at cutaneous vasodilator nerve enclings.

References.

BULBRISG, E. and J. BURS: J. Physiol. 1935. 83. 483. .--, Ibidem 1936. 87. 254. -, Ibidem 1937. 88. 341. POLKOW, B. and B. Uvs:is, Acta Physiol. Scand. 1848. 15. 365. -, Ibidem. 1948. 15. 389. -, K. H-ZGER and B. UvsXs, Ibidem. 19-18. 15. 401. --, 5. FROST and R. UrsXs, Ihiclem. 1918. 2-5. 412. - , , K. HBGER and B. UrsXs, Ibidem. 1948. 2 5 . 421.