TY - JOUR T1 - COMPARISON OF THE BLOCKADE PRODUCED BY DIBENZYLINE, ILIDAR, TOLAZOLINE AND PHENTOLAMINE OF THE VASOMOTOR RESPONSES IN SKIN INDUCED BY SYMPATHETIC NERVE STIMTULATION WITH THE BLOCKADE OF ITS RESPONSES TO L-EPINEPHRINE AND L-NOREPINEPHRINE JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 218 LP - 230 VL - 112 IS - 2 AU - Harold D. Green AU - John A. MacLeod AU - David A. Anderson AU - Adam B. Denison, Jr. Y1 - 1954/10/01 UR - http://jpet.aspetjournals.org/content/112/2/218.abstract N2 - In 33 dogs, anesthetized with sodium pentobarbital, blood flow to the skin bed of the hind limb was recorded with an electromagnetic flowmeter while perfusion pressure was recorded simultaneously with a strain gauge. The ipsilateral lumbar sympathetic chain was exposed retroperitoneally and stimulated at L3, L4 and L5 with monophasic 20 per second, 15 millisecond, 4 volt square wave pulses, and 0.1, 1.0 and 10.0 microgm. injections of l-epinephrine and l-norepinephrine were given intraarterially before and, again, after each injection of one of the blocking drugs. The blocking drugs were given intra-arterially in logarithmically increasing doses of 0.01, 0.03, 0.1, etc., to 30 mgm./kgm. Only one blocking drug was used in a given experiment. The blocking drugs studied were: Dibenzyline, phentolamine (Regitine), tolazoline (Priscoline), and Ilidar. The control responses to sympathetic and adrenergic stimulation were always pure vasoconstriction. The cutaneous bed was ten times more sensitive than the muscle bed to adrenergic stimulation. The constrictor response to l-epinephrime was of the same magnitude but significantly longer than was the response to l-norepinephrine. Small doses of the adrenergic blocking drugs (0.01 to 0.03 mgm./kgm. of Dibenzyline or phentolamine, and 0.01 to 0.3 mgm./kgm. of tolazoline or Ilidar), which reverse the response to l-epinephrine in skeletal muscle, reduced only slightly the vasoconstrictor responses to sympathetic and adrenergic stimulation in the skin. On the average, moderate doses (0.5 mgm./kgm. of Dibenzyline, 0.18 mgm./kgm. of phentolamine, and 1.5 mgm./kgm. of tolazoline or of Ilidar) were required to block the constrictor response to 0.1 microgm. of l-epinephrine and l-norepinephrine. After this dose of Dibenzyline or phentolamine vasodilation occurred in two-thirds of the animals in response to 0.1 and 1.0 microgm. of l-norepinephrine. At these doses sympathetic nerve stimulation continued to cause significant vasoconstriction and in no instance was there a dilator response. Large doses of the blocking drugs blocked the constrictor response to sympathetic nerve stimulation (on the average: 1.0 mgm./kgm. of Dibenzyline, 3.0 mgm./kgm. of phentolamine, 10.0 mgm./kgm. of tolazoline, and 30.0 mgm./kgm. of Ilidar). In no instance was a reversal (dilator response) unmasked. This dose level was approximately the same as that required to block the constrictor response to 10.0 microgm. of either l-epinephrine or of l-norepinephrine. At this dose level of Dibenzyline and phentolamine l-norepinephrine, in all doses, continued to produce a vasodilation in two-thirds of the animals. This dilator response was abolished by approximately a ten-fold further increase in the dose of these two blocking drugs. In no instance was a significant vasodilation response to l-norepinephrine obtained after tolazoline or Ilidar at the above mentioned doses. At the level of Dibenzyline or phentolamine blockade which abolished sympathetic nerve responses, the 10.0 microgm. dose of l-epinephrine caused a delayed vasodilator response which was interpreted as due to an effect of a hormone-like substance (possibly lactic acid) resulting from a systemic effect (as contrasted to a local effect) of the l-epinephrine. This effect was almost but not completely abolished by ten-fold further increase in the dose of the blocking drug. Our observations would suggest that, in contrast to skeletal muscle, an epinephrine-like rather than a norepinephrine-like substance may be the neuroeffector mediator for sympathetically induced vasoconstriction in skin. ER -