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Biomedical subjects

A D Watts

Publications and source records attributed to A D Watts.

24 records · Page 2Linked to original sources
PubMed1981

Modification of the vasomotor actions of methysergide in the femoral arterial bed of the anaesthetized dog by changes in sympathetic nerve activity.

1 Methysergide has been shown to have a remarkably selective vasoconstrictor action in the carotid arterial bed of the anaesthetized dog following intravenous administration. However we have now shown that under conditions which produce sympathetic blockade methysergide will also constrict the femoral arterial bed and the mechanism involved has been investigated. 2 Methysergide (10.100 microgram/kg i.v.) produced small but variable effects on femoral arterial blood flow in the anaesthetized dog. However following ganglion blockade (mecamylamine 5 mg/kg i.v.), section of the lumbar sympathetic chain between L4-L5 or catecholamine depletion with syrosingopine, methysergide consistently caused dose-related decreases in femoral arterial flow which were associated with increases in femoral arterial vascular resistance. 3 Intravenous infusion of methysergide (10 microgram/kg/min) or 5-hydroxytryptamine (5-HT, 10 microgram/kg/min) inhibited the increases in femoral arterial vascular resistance produced by stimulation of the lumbar sympathetic chain by 70% and 44% respectively whilst increases in vascular resistance produced by close intra-arterially administered noradrenaline were potentiated by 25% and 11% respectively 4 Our results show that the vasomotor actions of methysergide in the dog femoral arterial bed are dependent on the degree of sympathetic activity. This suggests that in the dog the post-junctional vasoconstrictor action of methysergide can be masked by a pre-junctional inhibitory effect on sympathetic nerves which may be mediated through stimulation of a specific pre-junctional receptor for 5-HT.

Anesthesia↗
PubMed1981

A pre-junctional action of 5-hydroxytryptamine and methysergide on noradrenergic nerves in dog isolated saphenous vein.

Electrical stimulation (2 Hz for 2 min) of dog isolated saphenous vein strips pre-incubated with tritiated noradrenaline increased the overflow of tritium of which about 80% was noradrenaline. 5-Hydroxytryptamine (5-HT; 1.0 x 10-9-1.0 x 10-7 mol litre-1) and methysergide (3.0 x 10-8-3.0 x 10-6 mol litre-1) inhibited the induced overflow of total tritium by a maximum of 78 +/- 4% and 47 +/- 7% respectively (mean +/- s.e. mean, n=6 for each). Methysergide was about 30 times less potent than 5-HT and the maximum inhibition obtained was less than with 5-HT. Both compounds inhibited electrically-induced contractions and overflow of tritiated noradrenaline. Their inhibitory actions on tritium overflow were little affected by phentolamine (1.0 x 10-6 mol litre-1) or cyproheptadine (1.0 x 10-6 mol litre-1), nor was the inhibitory effect of methysergide on electrically induced contractions antagonized by atropine, mepyramine, cimetidine or propranolol. The findings suggest that the prejunctional inhibitory effect of methysergide may be mediated via stimulation of a 5-HT receptor which, unlike the D-receptor, is not blocked by cyproheptadine. The possibility that the pre-junctional 5-HT receptor in the dog saphenous vein is the same as the post-junctional receptor in this preparation is discussed.

Animals↗
PubMed1979

Presynaptic inhibitory action of 5-hydroxytryptamine in dog isolated saphenous vein.

1 The effect of 5-hydroxytryptamine on contractile responses to sympathetic nerve stimulation has been studied in the dog isolated saphenous vein.2 Electrical stimulation (0.1 to 10 Hz) of dog saphenous vein strips produced frequency-dependent contractions. Contractions produced by stimulation at 2 Hz were almost completely blocked by tetrodotoxin (3.1 x 10(-8) mol/l) or phentolamine (5.0 x 10(-6) mol/l) but mecamylamine (5.0 x 10(-6) mol/l) had little effect. This suggests that the contractions were mediated predominantly through noradrenaline release from postganglionic noradrenergic nerves.3 Contractions produced by intermittent electrical stimulation at 2 Hz were inhibited by 5-hydroxy-tryptamine (1.0 x 10(-9) to 1.0 x 10(-7) mol/l) in a concentration-dependent manner whilst contractions induced by exogenous noradrenaline were not affected.4 The inhibitory action of 5-hydroxytryptamine was most marked at low frequencies of stimulation and with low pulse numbers.5 High external calcium concentrations (3.9 and 5.2 x 10(-3) mol/l) reduced the inhibitory action of 5-hydroxytryptamine.6 Cyproheptadine (1.0 x 10(-8) mol/l to 1.0 x 10(-6) mol/l) or morphine (1.0 x 10(-7) mol/l to 1.0 x 10(-5) mol/l) did not antagonize the inhibitory action of 5-hydroxytryptamine. Methysergide (1.0 x 10(-7) mol/l) slightly reduced the contractions produced by electrical stimulation and only weakly antagonized the action of 5-hydroxytryptamine.7 It is suggested that a 5-hydroxytryptamine receptor exists presynaptically in the dog isolated saphenous vein strip and that stimulation of this receptor by low concentrations of 5-hydroxytryptamine inhibits the release of noradrenaline from noradrenergic nerves. This receptor type is resistant to blockade by ;classical' 5-hydroxytryptamine antagonists.

Animals↗