Noradrenergic component in the vasoconstriction induced by 5-hydroxytryptamine in goat cerebral arteries

5-Hydroxytryptamine (5-HT) elicited dose-dependent increases in tension in the middle cerebral artery of the goat, which were significantly antagonized by lysergic acid diethylamide (LSD, 10(-8) M) and methysergide (10(-7) M). In the presence of phentolamine (10(-6) M), the dose-response curve to 5-HT was shifted to the right, the pA2 value for this antagonism was 6.52. Pretreatment of goats with reserpine (0.02 mg kg-1 day-1 for three days) or removal of both superior cervical ganglia 15 days before the experiment brought about a significant decrease in the vasoconstriction induced by doses of 5-HT higher than 10(-7) M. The remaining contraction produced by 5-HT in arterial segments from reserpinized or gangliectomized goats was further reduced in the presence of LSD. In addition, high concentrations of 5-HT induced tritium release from goat pial arteries preloaded with (-)-[3H]noradrenaline, 2 X 10(-7) M) which was significantly decreased in vessels from gangliectomized or reserpinized goats. These results in goat cerebral arteries indicate that in the contraction evoked by 5-HT there are two components. The first appears with low concentrations (up to 10(-7) M) in which 5-HT acts directly on 5-HT receptors. The second occurs at high doses (greater than 10(-7) M) in which 5-HT also acts indirectly on alpha-adrenoceptors by release of noradrenaline from noradrenergic nerve endings.     

Response of Rabbit Ear and Femoral Arteries to 5-Hydroxytryptamine During Cooling

The effects of cooling on the response of cutaneous and non-cutaneous arteries to 5-hydroxytryptamine (5-HT) were analysed. Segments 2-mm long from rabbit central ear (cutaneous) and femoral (non-cutaneous) arteries were prepared for isometric tension recording in an organ bath at 37 and 24°C (cooling). 5-HT (10^?9-3 times 10^?4 M) induced concentration-dependent contraction of the arteries. The sensitivity and maximal contraction of ear arteries and only the maximal contraction of femoral arteries to this amine were reduced at 24°C. Endothelium removal or pretreatment with the nitric oxide synthase inhibitor N^G-nitro-l -arginine methyl ester (l -NAME, 10^?5 m ) did not affect the response at 37°C but reversed the decreased sensitivity at 24°C in ear arteries, and neither procedure modified the reactivity at 24 or 37°C in femoral arteries to 5-HT. At both temperatures, the response of ear arteries to 5-HT was shifted to the right by phentolamine (10^?6M) more than by the 5-HT antagonist, ketanserin (3 times 10^?7M), and that of femoral arteries was shifted to the right by ketanserin or the 5-HT₁/5-HT₂ antagonist methysergide (3 times 10^?7 M) more than by phentolamine, in arteries with and without endothelium. These data concur with the proposition that the contraction to 5-HT is mediated mainly by α-adrenergic receptors in ear arteries and mainly by 5-HT-ergic receptors in femoral arteries, and suggest that cooling reduces the sensitivity of cutaneous, but not of deep arteries to 5-HT, probably by endothelium-nitric oxide-dependent mechanisms.     

Release of [3H]noradrenaline induced by 5-hydroxy-tryptamine from cat pial arteries

Pial arteries of cats were used to analyse the effects of 5-hydroxytryptamine (5-HT) on the release of [³H]noradrenaline. To achieve this the vessels were preincubated with [³H]noradrenaline and the effect of different concentrations of 5-HT (10^?6, 10^?5, 10^?4 M) on the release of tritium was studied. 5-HT elicited release of radioactivity in a dose-dependent manner. Removal of both superior cervical sympathetic ganglia 15 days before the experiment or pretreatment of the animals with reserpine (3 mg kg^?1, total dose) produced a significant decrease in the outflow of tritium induced by 5-HT. In these arteries, the amount of radioactivity retained at the end of the experiment was much diminished. Cocaine (10^?6 M) caused a significant decrease in the tritium efflux induced by 5-HT (10^?5 M). These results show that 5-HT has an indirect adrenergic effect in the pial arteries of the cat only at high doses of 5-HT, and confirm that sympathetic innervation of these vessels mainly comes from the superior cervical ganglia.     

Interference of pentobarbitone with the contraction of vascular smooth muscle in goat middle cerebral artery

Pentobarbitone (10^?5 to 10^?3 M) decreased the basal tone of vascular smooth muscle of goat middle cerebral artery in a dose-dependent manner as well as relaxing established contractions induced by noradrenaline (NA) (10^?5 M), 5-hydroxytryptamine (5-HT) (10^?5 M) and KCl(120 mM). Preincubations with pentobarbitone reduced the contractions evoked by these three agents in a dose-dependent way. It also decreased Ca²⁺-induced contractile responses in K⁺-depolarized arteries and 5-HT-Ca²⁺ and NA-Ca²⁺ contractions dose-dependently. Contractions induced by K⁺ were more sensitive to the depressant actions of the drug than those produced by NA and 5-HT. The small contractions evoked by K⁺ and 5-HT in Ca²⁺-free medium were also reduced in its presence. The antagonism Ca²⁺-pentobarbitone was insurmountable. These results suggest that the drug interferes with Ca²⁺ entry and Ca²⁺ release from cell stores, and therefore with the smooth muscle contractions.     

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 × 10^?9-1·0 × 10^?7 mol litre^?1) and methysergide (3·0 × 10^?8-3·0 × 10^?8 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 × 10^?8 mol litre^?1) or cyproheptadine (1·0 × 10^?8 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.     

Characterization of 5-Hydroxytryptamine receptors in goat cerebral arteries

• 1.1. In isolated goat middle cerebral artery segments, 5-hydroxytryptamine (5-HT, 10⁻⁸-3 × 10⁻⁵ M) elicited concentration-dependent contractions with EC₅₀ = 2.1 (1.9−2.5) × 10⁻⁷ M and E_max = 64 ± 2% of 50 mM KCl-induced contraction.
• 2.2. Several 5-HT receptor agonists were used: (a) the agonist of 5-HT₂ receptors α-methyl-5-hydroxytryptamine (10⁻⁷ -3 × 10⁻⁴ M) induced strong contraction (51± 6%); (b) the selective agonists of 5-HT_1A receptors sumatriptan (10⁻⁸ - 10⁻⁵ M) and 5-carboxamidotryptamine (10⁻⁹ - 10⁻⁴ M) and the agonist of 5-HT_1A receptors 8-hydroxy-2-(di-n-propylamino)tetralin (10⁻⁷ - 3 × 10⁻⁵ M) induced weak contractions (8, 18 and 14%, respectively); and (c) the agonist of 5HT₃ receptors 2-methyl-5-hydroxytryptamine (3 × 10⁻⁶ - 10⁻⁴ M) induced almost negligible contraction.
• 3.3. Pretreatment with the antagonist of 5-HT_1A and 5-HT_1B receptors cyanopindolol (10⁻⁸, 10⁻⁶ M), the antagonist of 5-HT₁/5-HT₂ receptors methysergide (10⁻¹¹, 10⁻⁹ M) and the antagonist of 5-HT₂ receptors ketanserin (10⁻¹¹, 10⁻⁹ M) induced non-competitive inhibition of the concentration-response curve to 5-HT. The antagonist of 5-HT₃ receptors 3-trophanyl-3,5-dichlorobenzoate (10⁻⁷, 10⁻⁵ M) did not inhibit the contractile curve to 5-HT.
• 4.4. These results suggest that 5-HT contracts the goat middle cerebral artery by acting mainly on 5-HT₂ receptors.

     

乙酰天麻素对血管平滑肌的解痉作用

天麻属兰科植物,近年来从天麻中提出一个有效成分天麻素,经实验及临床观察认为是安全有效的镇静药。对神经衰弱,血管神经性头痛等可使症状减轻或消除。昆明制药厂对天麻素的结构进行了改造,合成了一系列的衍生物,其中乙酰天麻素(acetagastrodine,G2)作用比天麻素强,本文研究乙酰天麻素对血管平滑肌的影响。     

Analysis of the contractile effect of 5-hydroxytryptamine on the isolated posterior communicating artery of the cat

5-Hydroxytryptamine (5-HT) induced dose-dependent increases in tension on the isolated posterior communicating artery (PCA) of the cat were significantly antagonized by lysergic acid diethylamide (LSD, 6 times 10^?9 m). In the presence of phentolamine (10^?6 m) the contraction induced by the two lowest doses of 5-HT was significantly reduced. Pretreatment of the animals with reserpine (3 mg kg^?1, i.p., total dose) did not modify the dose-response curve to 5-HT except for the lowest dose. Removal of both superior cervical sympathetic ganglia 15 days before the experiment brought about a significant increase in the vasoconstriction induced by 5-HT at all the doses compared with the control. Cocaine (10^?6m) induced a significant shift to the left of the dose-response curve to 5-HT but the maximum response was the same as in the control. The augmented response to 5-HT after denervation was partially antagonized by LSD (6 times 10^?9 m) but not by phentolamine (10^?6 m). These results show that the vasoconstriction elicited by 5-HT in the PCA of the cat is mainly due to direct stimulation of tryptaminergic receptors. The participation of an indirect adrenergic component in the contractile effects of 5-HT seems to be negligible.     

Inhibition of adrenergic neurotransmission by prostaglandin E1 (PGE1) in the rabbit ear artery.

Isolated central ear arteries of rabbits were perfused with Krebs solution at a constant flow rate of 2–7 ml/min. Pressure changes to periarterial nerve stimulation (1, 3, 10 and 30 Hz; 5–32 pulses) and to noradrenaline were measured in the presence and absence of prostaglandin E₁ (PGE₁). This substance in concentrations of 7 × 10^?9– 4.5 × 10^?7 produced a dose-dependent inhibition of constrictor responses to nerve stimulation. The degree of inhibitory action of PGE₁ became progressively less as the frequency or length of stimulation was increased. Prostaglandin E₁ (1.1 × 10^?7 M) failed to affect the constrictor responses to noradrenaline and it markedly reduced the stimulation-evoked release of radioactivity from arteries incubated with [³]noradrenaline. The results indicate that PGE₁ inhibits the vasoconstrictor responses of rabbit ear artery to nerve stimulation by reducing the release of the adrenergic transmitter.     

Effects of nicotine on the uptake and retention of 14C-noradrenaline and 14C-5-hydroxytryptamine by rat brain homogenates

The effects of nicotine on the uptake and retention of noradrenaline (NA) and 5-hydroxytryptamine (5-HT) by homogenates prepared from rat hypothalamus or hippocampus have been studied. Samples of homogenate from both brain regions were incubated with ¹⁴C-NA or ¹⁴C-5-HT and a fraction containing the synaptosomes was isolated by ultrafiltration. The uptake of ¹⁴C-NA and ¹⁴C-5-HT by hypothalamus and hippocampus was inhibited and the retention of both putative transmitters decreased by “high” concentrations of nicotine (5 × 10^?3 M and 5 × 10^?4 M). At lower concentrations (5 × 10^?5 M and 5 × 10^?6 M), a specific response to nicotine was observed. The initial uptake of ¹⁴C-NA was increased and the retention decreased by nicotine, particularly in the hypothalamus, in contrast to the inhibition of ¹⁴C-5-HT uptake by both hypothalamus and hippocampus.     

Methysergide induces selective potentiation in cholinergic contractions of the guinea-pig vas deferens by facilitating acetylcholine release

Methysergide (3 times 10^?6 M) enhanced the contractile responses of the isolated stripped vas deferens of guinea-pig to acetylcholine(ACh) and arecoline, but not those to noradrenaline, tyramine and bradykinin. Methysergide (3 times 10^?5 M) suppressed the contraction elicited by noradrenaline or histamine. The methysergide-induced potentiation of the response to ACh was prevented by pre-addition of hemicholinium but not by tetrodotoxin or morphine. The augmentation of the response to ACh by physostigmine was unaffected by hemicholinium. The phasic contraction of the tissue elicited by 30 mM KCl was also enhanced by methysergide, and this enhancement was prevented by the pre-addition of atropine (1·4 times 10^?7 M). In the depolarized vas deferens after exposure to 30 mM KCl, methysergide occasionally induced a sustained tonic contraction which was inhibited by atropine. These findings suggest that methysergide facilitates a release of ACh by acting on the cholinergic nerve terminals and selectively potentiates the cholinergic response.     

Caffeic acid phenethyl ester attenuates IgE-induced immediate allergic reaction

Caffeic acid phenethyl ester (CAPE) is the active component of honey bee propolis extracts. The results of the current study demonstrate that CAPE attenuated immunoglobulin (Ig)E-mediated allergic response in mast cells. Oral administration of CAPE inhibited IgE-mediated passive cutaneous anaphylaxis. CAPE effectively reduced both histamine and serotonin (5-HT)-induced vascular permeability in rats. CAPE also reduced histamine and leukotrienes (LTs) release from isolated rat peritoneal mast cells. Moreover, CAPE suppressed contraction induced by histamine (3 × 10^?8–3 × 10^?5 M), 5-HT (3 × 10^?9–10^?6 M) and adenosine (3 × 10^?8–10^?5 M) in guinea pig tracheal zigzag. These findings provide evidence that CAPE may serve as an effective therapeutic agent for allergic diseases.     

Mechanisms Involved in Electrically-induced Responses of Rat Seminal Vesicles

Contractile responses of rat isolated seminal vesicle were elicited by electrical field stimulation (EFS, 10 Hz, 1 ms, 40 V for 5 s), noradrenaline (1 times 10^?5 m ) and carbachol (1 times 10^?5 m ). Guanethidine (2 times 10^?5?5 times 10^?4 m ) progressively reduced the contraction induced by EFS and carbachol to 24 ± 2 and 10 ± 2%, respectively, at the highest concentration (n = 6), while potentiating noradrenaline contraction to a maximum of 154 ± 14% at 2 times 10^?5 m (n = 6). Prazosin (1 times 10^?6 m ) and atropine (2·5 times 10^?7 m ) completely abolished the response to the corresponding agonist and each reduced the response to EFS to 64 ± 8 and 61 ± 3%, respectively (n = 6). In the presence of both atropine and prazosin a small contraction to EFS remained (14 ± 4%, n = 6), which is unlikely to be due to ATP, since exogenous ATP did not induce a contractile response and had an inhibitory effect on EFS-induced responses. Clonidine (1·25 times 10^?5 m ) completely blocked responses to noradrenaline and reduced the response to EFS to 68 ± 7% (n = 6). However, when both the adrenergic and cholinergic components of EFS were blocked by prazosin and atropine, clonidine potentiated the remaining response to EFS (323 ± 82%, n = 4). Yohimbine (1 times 10^?5 m ) blocked the response to noradrenaline and reduced the response to EFS to 37 ± 5% (n = 6) while the carbachol response was unaffected. Both cholinergic and noradrenergic components contribute to the response to EFS but there appears to be little involvement of presynaptic α₂-adrenoceptors in regulating neurotransmitter release. The actions of clonidine and yohimbine are compatible with the suggestion that their effects are due to postsynaptic α₁-adrenoceptor blockade.     

Reassessment of the blocking activity of prazosin at low and high concentrations on sympathetic neurotransmission in the isolated mesenteric vasculature of rats

1 The overflow of endogenous noradrenaline from the rat mesenteric arterial vasculature was determined along with the perfusion pressure response to periarterial nerve stimulation (PNS) (4–12 Hz). 2 The PNS-induced pressor responses were blocked by prazosin at 3x 10⁸ M but not by prazosin at 10^?6 M or the combination of prazosin at 3 × 10^?8 M and yohimbine (10^?7 M). 3 The PNS-induced overflow of endogenous noradrenaline was significantly augmented by prazosin at 10^?6 M or the combination of prazosin at 3 × 10^?8 M and yohimbine (10^?7 M) but not by prazosin at 3 × 10^?8 M alone. 4 The PNS-induced pressor response and endogenous noradrenaline overflow, in the absence of prazosin, were not significantly influenced by α, β-methylene-adenosine triphosphate (α, β-methylene ATP) (3x10^?6 M). The pressor responses to PNS which remained after prazosin at 10^?6 M were abolished by pretreatment with α, β-methylene ATP and therefore attributable to coreleased ATP. 5 The pressor responses to exogenous noradrenaline were abolished by prazosin at both 3 × 10^?8 M and 10^?6 M. 6 These results suggest that no functionally significant amount of ATP was coreleased with noradrenaline by PNS in the presence of prazosin at low concentrations which blocked only postjunctional α₁-adrenoreceptors. 7 Thus, these results indicate that the effects of prazosin at high concentrations, such as 10^?6 M, on sympathetic neurotransmission should not be ignored when considering the mechanisms of vasoconstrictor responses to PNS following high concentrations of prazosin.     

Studies on the action and mechanism of action of oxyfedrine on isolated tracheal chains

Oxyfedrine, a β-sympathomimetic drug, did not affect isolated rat and rabbit trachea in concentration from 2.86 × 10^?8 to 2.86 × 10^?4 M, but on the guinea-pig trachea, it caused a dose dependent relaxation of natural tone in lower concentrations (1.79 × 10^?7 to 2.86 × 10^?6 M. In higher concentrations (1.14 × 10^?5 to 2.86 × 10^?4 M), however, a contraction was observed, which was also dose dependent. This contraction was not affected by atropine, lysergic acid diethylamide or by pretreatment with reserpine but was blocked by antihistaminics (isothipendyl and clemastine). Adrenaline, noradrenaline, phenylephrine and isoprenaline did not contract the guinea-pig trachea, whereas contractions were observed after high concentrations of norephedrine, amphetamine, ephedrine and tyramine. These contractions were also unaffected by reserpine pretreatment.It is concluded that the contraction of the guinea-pig trachea by oxyfedrine is related to its structural relationship to the phenylethylamines and might be due to histamine release, an action on histamine receptors or a histamine-like action.     

No evidence for reverse trans-synaptic regulation of neuronal uptake by beta-adrenoceptors in kitten atria

Kitten atria incubated with [³H]noradrenaline, 1.18 × 10^?7 M for 10 min or 3 × 10^?9 M for 30 min, actively accumulated the amine. Final tissue tritium concentrations were 2–4-fold and 8–12-fold higher, respectively, than those of the incubation fluid. Uptake was consistently greater in right than in left atria. The β₁-adrenoceptor antagonist, practolol, 10^?6 or 10^?5 M, and the β₁- and β₂-adrenoceptor antagonist, propranolol, 5 × 10^?8, 5 × 10^?7or 5 × 10^?6 M, did not affect noradrenaline uptake. Reverse trans-synaptic regulation of neuronal noradrenaline uptake by β-adrenoceptors therefore does not appear to operate in kitten atria as has been reported for rat atria and other tissues.     

Characterization and radioautography of [3H] LSD binding by rat brain slices in vitro: The effect of 5-hydroxytryptamine

Binding of D-[³H] lysergic acid diethylamide (LSD) to rat coronal brain slices and its blockade by 5-hydroxytryptamine (5-HT) had characteristics similar to those of brain homogenates in respect of K_D, kinetics and reversibility of binding. Radioautography was done on slices that had been incubated in 6 nM [³H] LSD and on adjacent slices incubated in the same concentration of tritiated LSD plus 10^?5 M of 5-HT. Choroid plexus showed densest labeling of [³H] LSD. In neuropil, dense labeling occurred within parts of the hippocampal formation except for fields CA2 and CA3 which were sparsely labeled. All layers of the cortex except the posterior cingulate gyrus were labeled by LSD. 5-HT blocked labeling of choroid plexus, hippocampal formation, septum, pons, medulla and parts of cortex but only reduced labeling of most other structures. LSD binding sites may relate to some of its pharmacological effects.     

The in vitro uptake of biogenic amines by snail (Heliz pomatia) nervous tissue.

The uptake of [³H]5-HT, [³H]dopamine, [³H]noradrenaline and [³H]octopamine into the suboesophageal ganglia of the snail, Helix pomatia, was studied. When tissues were incubated at 25° in mediums containing radioactive amines, tissue: medium ratios of about 30:1, 18: l, 4:1 and 5:1 for 5-HT, dopamine, noradrenaline and octopamine respectively were obtained after 20–30 min incubation. Tissues incubated at 25° in mediums containing radioactive amines for 20–30 min showed that 90% of the radioactivity was present as unchanged [³H]5-HT, [³H]dopamine, [³H]noradrenaline or [³H]octopamine. The high tissue : medium ratios for 5-HT and dopamine, but not for noradrenaline and octopamine, demonstrated saturation kinetics which were dependent upon temperature and sodium ions. From the Lineweaver-Burk plots, two uptake mechanisms for 5-HT at 25° were resolved, the high affinity uptake process having a K_m1valueof 8.48 × 10^?8 M and V_max1 value of 0.077 nmole/g per min, while the lower affinity process had a K_m2 value of 1.8 × 10^?6 M and a V_max2 value of 0.66 mole/g per min. At 0° a single uptake mechanism for 5-HT occurred which gave a K_m value of 0.152 × 10^?8 M and a V_m value of 0.0203 nmole/g per min. In the case of dopamine, the Lineweaver-Burk plot of 25° showed a single uptake process with values for K_m and V_max of 1.02 × 10^?7 M and 0.0673 nmole/g per min respectively. This process did not function at 0°. The effects of various agents and ions upon the accumulation processes for all amines were also studied, and the findings indicate that the same neurons may well accumulate more than one amine type. It is concluded that 5-HT and dopamine uptake in the snail ganglia is a mechanism for inactivating these substances at 25° and that an uptake mechanism for 5-HT also functions at 0°. The present results are discussed from the point of view of the monoamines having transmitter functions in the snail CNS.     

Effect of nomifensine (HOE 984), a new antidepressant, on uptake of noradrenaline and serotonin and on release of noradrenaline in rat brain synaptosomes

Nomifensine (8-amino-2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline hydrogen maleate) is a thymoleptic drug with a moderate centrally stimulating component. Its effects on noradrenaline (NA) and serotonin (5-HT) uptake by crude synaptosome preparations from both whole rat brain and from hypothalamus have been studied and compared with those of several tricyclic antidepressants and d-amphetamine. Nomifensine inhibition of NA uptake by synaptosomal fractions from rat hypothalamus (IC₅₀ = 7.0 × 10^?7 M) was similar to that of nortriptyline and protriptyline. In contrast to tricyclic antidepressants, nomifensine was found to be a powerful inhibitor of NA uptake in synaptosomes obtained from whole brain (IC₅₀ = 9.0 × 10^?8 M). Nomifensine had only a moderate effect on 5-HT accumulation (IC₅₀ = 2.8 × 10^?5 M), comparable with that of desipramine. The inhibition of uptake of both NA and 5-HT by nomifensine was of a competitive type. It is suggested that the centrally stimulating component of nomifensine, which is lacking in most thymoleptic drugs, is based upon its strong inhibition of catecholamine re-uptake into noradrenergic as well as dopaminergic nerve endings. Nomifensine has no releasing effects on the efflux of NA from rat brain synaptosomes, thus differing clearly from d-amphetamine and other indirectly acting sympathicomimetic agents.     

The Effect of Nifedipine on Isolated Human Peripheral Vessels

Abstract Isometric tension was recorded in ring preparations of human peripherial arteries and veins contracted by potassium (127 mM) and noradrenaline (1.8 × 10^-5 M). In the veins, nifedipine had a marked relaxing effect on contractions induced by both agents, and also reduced the contractile amplitude when added prior to stimulation. The inhibiting effect of nifedipine was more marked on the potassium than on the noradrenaline-evoked responses. This was in contrast to verapamil, which inhibited the noradrenaline-induced contractions significantly more, than those produced by potassium. After immersion of the vein preparations in calcium-free medium for 30 min., the potassium contracture decreased to 26±2.0% (mean ± S.E.M.) of the response in normal Krebs solution, and the noradrenaline-evoked response to 7.1±0.8%. The responses to both agents were completely restored when the calcium concentration was increased from 0 to 4 mM. Nifedipine (1.5 × 10^-7 M) depressed the potassium contracture in calcium-free solution to 7.3±1.6%, and the noradrenaline response to 5.5±1.6%; on addition of calcium, the response elicited by potassium increased to 16±1.7%, and that by noradrenaline to 56±8.6%. Compared with its actions on the veins, the effect of nifedipine on the arterial preparations was less pronounced. In the arteries, too, the inhibiting effect of nifedipine was significantly more pronounced on the potassium than on the noradrenaline-induced contraction. Immersion for 30 min. in calcium-free medium reduced the response to potassium to 61±6.0% and that to noradrenaline to 68±5.6% of the control in normal Krebs. Nifedipine (2.9 × 10^-7 M) further reduced the potassium contraction to 20±4.0%; the response to noradrenaline was unaffected, being 74±6.4% of the control.