European Journal o f Pharmacology, 45 (1977) 69--72 © Elsevier/North-Holland Biomedical Press

69

Short communication N O R A D R E N A L I N E R E V E R S A L IN CANINE SUBCUTANEOUS ADIPOSE TISSUE R O G E R E. P A R K E R

Department o f Physiology and Pharmacology, The Bowman Gray School o f Medicine o f Wake Forest University, Winston-Salem, North Carolina 27103, U.S.A. Received 10 May 1977, accepted 16 June 1977

R.E. PARKER, Noradrenaline reversal in canine subcutaneous adipose tissue, European J. Pharmacol. 45 (1977) 69--72. Although adrenaline reversal is a well known phenomenon, fewer investigations have demonstrated reversal of the vascular response to noradrenaline (NA). The present studies compared subcutaneous adipose tissue vascular responses to intraoarterial NA with those of sympathetic nerve stimulation. Both NA and electrical stimulation produced vasoconstriction in adipose tissue which was reversed to ~-adrenergicaily mediated vasodilation following local ~-adrenergic block. Noradrenaline

Adipose tissue

Noradrenaline reversal

1. Introduction

2. Materials and methods

There is general agreement that the sympathetic nervous system plays an important role in the regulation o f blood flow and lipid mobilization in adipose tissue (Fredholm, 1970). Reports of previous investigations have shown that electrical stimulation of sympathetic nerves induced a stimulus-frequency d e p e n d e n t vasoconstriction (see review b y Rosell, 1969). The vasoconstriction was blocked b y dihydroergotamine and other a-adrenoreceptor antagonists. Stimulation following a-adrenergic blockade resulted in an increase in blood flow which was blocked b y ~-adrenoreceptor blocking drugs. Since stimulation of sympathetic nerves normally produces vascular responses through liberation of intraneuronal NA, the present study sought to compare the effects of nerve stimulation with those observed following intra-arterial injections of NA.

Seven adult female mongrel dogs, 19.5-24.5 kg, were used in this study. Anesthesia was accomplished with intravenous chloralose, 80 mg/kg. The right inguinal fat pad was vascularly isolated and perfused at constant flow from reservoirs containing arterial blood as described b y RoseU (1966). Fat pad perfusion pressure was measured from a side-arm in the arterial perfusion cannula with a Statham transducer and venous outflow was measured b y means of drop rate counter. The fat pads studied ranged in weight from 40.5 to 103 g and flow ranged from 3.8 to 11.9 ml/ 100 g wet tissue wt/min. The nerve to the adipose tissue was cut and stimulated for 2 min at 8 V, 5 msec pulse duration and 2, 4 and 10 Hz. NA (levarterenol bitartrate), 0.5 pg base, was administered in 0.1 ml Ringer injection via a rubber-capped injection port in the arterial perfusion can-

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R.E. P A R K E R

nula. Dihydroergotamine (D.H.E.), 400 #g, and propranolol, 500 #g, were administered in divided doses via the same injection system. Each response was compared to its prestimulus or pre-injection control using Student's t-test for paired observations.

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3. Results

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Intra-arterial administration of NA consistently resulted in vasoconstriction in the constant blood flow, reservoir perfused adipose tissue studied (fig. 1). The duration of the response ranged from 1.5 to 3 min. Often perfusion pressure fell to below control values before returning approximately to pre-injection levels. Following a-adrenergic block, the same NA dose by the same route o f administration always resulted in a fall in perfusion pressure. The vasodilator response to NA, unmasked by D.H.E. administration, was sensitive to propranolol blockade. Following combined a- and ~-adrenergic block, intraarterial NA continued to produce vasodilation in only 3 of the 7 animals studied; When considered as a group there was no statistical difference from the pre-injection control. Table 1 presents the results of electrical stimulation of the sympathetic nerve sup-

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Noradrenaline reversal in canine subcutaneous adipose tissue.

European Journal o f Pharmacology, 45 (1977) 69--72 © Elsevier/North-Holland Biomedical Press 69 Short communication N O R A D R E N A L I N E R E V...
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