Contraction Of Rat Tail Artery Research Articles

Modified cytoplasmic Ca2+ sequestration contributes to spinal cord injury-induced augmentation of nerve-evoked contractions in the rat tail artery.

In rat tail artery (RTA), spinal cord injury (SCI) increases nerve-evoked contractions and the contribution of L-type Ca2+ channels to these responses. In RTAs from unoperated rats, these channels play a minor role in contractions and Bay K8644 (L-type channel agonist) mimics the effects of SCI. Here we investigated the mechanisms underlying the facilitatory actions of SCI and Bay K8644 on nerve-evoked contractions of RTAs and the hypothesis that Ca2+ entering via L-type Ca2+ channels is rapidly sequestered by the sarcoplasmic reticulum (SR) limiting its role in contraction. In situ electrochemical detection of noradrenaline was used to assess if Bay K8644 increased noradrenaline release. Perforated patch recordings were used to assess if SCI changed the Ca2+ current recorded in RTA myocytes. Wire myography was used to assess if SCI modified the effects of Bay K8644 and of interrupting SR Ca2+ uptake on nerve-evoked contractions. Bay K8644 did not change noradrenaline-induced oxidation currents. Neither the size nor gating of Ca2+ currents differed between myocytes from sham-operated (control) and SCI rats. Bay K8644 increased nerve-evoked contractions in RTAs from both control and SCI rats, but the magnitude of this effect was reduced by SCI. By contrast, depleting SR Ca2+ stores with ryanodine or cyclopiazonic acid selectively increased nerve-evoked contractions in control RTAs. Cyclopiazonic acid also selectively increased the blockade of these responses by nifedipine (L-type channel blocker) in control RTAs, whereas ryanodine increased the blockade produced by nifedipine in both groups of RTAs. These findings suggest that Ca2+ entering via L-type channels is normally rapidly sequestered limiting its access to the contractile mechanism. Furthermore, the findings suggest SCI reduces the role of this mechanism.

Contribution of ATP-Sensitive K+ Channels to Contraction of Rat Tail Artery is Significantly Reduced in Males but Not Females Rats in Streptozotocin-Induced Diabetes: Pharmacological Analysis

The aim of this article is to find out possible gender differences of participation of ATP-sensitive potassium channels in regulation of contractility in vascular smooth muscles of rats with diabetes. We used isolated tail artery of both genders rats with streptazotocin-induced diabetes (SID). After 3 weeks, we compared concentration-effects curves obtained with phenylephrine (0.1 to 300 μM) in the presence of 100 μM of diazoxid in control and SID rats of both genders. Diazoxide at 100 μM concentration significantly antagonizes concentration-dependent contraction of tail artery induced by phenylephrine in both male and female control rats. However, this antagonism disappeared in male but not female rats treated by streptozotocin. Our results indicate that SID leads to downregulation or functional malformation (lack of reaction to the opener) of ATP-sensitive potassium channels in males, but not in females rats. This observation has to be confirmed by immunochemistry analysis and taking into account in humans.

In-vitro pharmacology of sarpogrelate and the enantiomers of its major metabolite: 5-HT2A receptor specificity, stereoselectivity and modulation of ritanserin-induced depression of 5-HT contractions in rat tail artery.

The new antiplatelet agent sarpogrelate (MCI-9042), its major metabolite (R,S)-1-[2-[2-(3-methoxyphenyl)ethyl]phenoxy]-3-(dimethylamino)-2- propanol ((R,S)-M-1) and the enantiomers of (R,S)-M-1 were studied as antagonists at 5-HT2A receptors, 5-HT1-like receptors, 5-HT3 receptors, alpha 1-adrenoceptors, beta-adrenoceptors, histamine H1 receptors, histamine H2 receptors and muscarinic M3 receptors in various functional in-vitro assays. Sarpogrelate, (R,S)-M-1, (R)-M-1 and (S)-M-1, respectively, were competitive antagonists of 5-hydroxytryptamine (5-HT) at 5-HT2A receptors of rat tail artery with calculated pA2 values of 8.53, 9.04, 9.00 and 8.81, respectively. Sarpogrelate lacked prominent 5-HT1-like, 5-HT3, beta, H1, H2 and M3 antagonist activity and weakly blocked alpha 1-adrenoceptors (pKB = 6.30). (S)-M-1 showed weak affinity for 5-HT1-like receptors (pKB = 6.30), alpha 1- (pKB = 6.80) and beta- (pKB = 6.54) adrenoceptors, while (R)-M-1 was a weak antagonist at histamine H1 receptors (pKB = 6.49). Stereoselectivity of M-1 enantiomers was low. (R)-M-1 showed 1.6-fold, 2,3-fold and 2.5-fold higher antagonist activity than (S)-M-1 for 5-HT2A, H1 and M3 receptor, respectively. Affinity at beta-adrenoceptors and 5-HT1-like receptors was 5-fold and 3-fold higher for (S)-M-1 than for (R)-M-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Rho-kinase-mediated regulation of receptor-agonist-stimulated smooth muscle contraction

Rho kinase was shown to regulate smooth muscle contraction through modulating myosin phosphatase (MLCP) activity, but the in vivo mechanism remains to be clarified. This study examined the effects of Rho kinase inhibition on the phosphorylation time course of MLCP subunit MYPT1 at Thr697 and Thr855 and MLCP inhibitory protein CPI-17 at Thr38 and on actin polymerization during the contraction of rat tail artery (RTA) smooth muscle. Rho kinase inhibitor Y27632 suppressed force activated by alpha(1)-adrenergic agonist phenylephrine or thromboxane A(2) analog U46619 with concomitant decreases in MLC(20) phosphorylation. Phenylephrine and U46619 significantly increased MYPT1(Thr855) phosphorylation that was eliminated by Y27632 pretreatment, whereas MYPT1(Thr697) phosphorylation was not stimulated. Phenylephrine increased CPI-17(Thr38) phosphorylation that was not inhibited by Y27632 but was abolished by a protein kinase C inhibitor Ro 31-8220; in contrast, U46619 did not stimulate CPI-17 phosphorylation. Both agonists increased actin polymerization that was diminished by Y27632 under phenylephrine but not U46619 activation. These results demonstrated a temporal correlation between MYPT1(Thr855) phosphorylation, MLC(20) phosphorylation, and contraction in a Rho-kinase-dependent manner for both phenylephrine and U46619 stimulation, suggesting that Rho kinase regulates MLCP activity through MYPT1(Thr855) phosphorylation during RTA smooth muscle contraction. Furthermore, Rho kinase regulates actin polymerization activated by alpha(1)-adrenoceptors but is less significant in thromboxane receptor stimulation.

Evidence that α 1B-adrenoceptors are involved in noradrenaline-induced contractions of rat tail artery

The present study characterizes the α 1-adrenoceptor subtypes mediating contractions to noradrenaline in isolated ring preparations of rat tail artery. Concentration–response ( E/[ A]) curves to noradrenaline were apparently monophasic (pEC 50 6.47) but became biphasic in the presence of the selective α 1A-adrenoceptor antagonist (±)-1,3,5-trimethyl-6-[[3-[4-((2,3-dihydro-2-hydroxymethyl)-1,4-benzodioxin-5-yl)-1-piperazinyl]propyl]amino]-2,4(1 H,3 H)-pyrimidinedione (B8805-033). Whereas the first phase of contraction to noradrenaline remained nearly unaffected in the presence of B8805-033 (0.03–3 μM), the second phase was concentration-dependently shifted to the right (p K B 8.06). In the presence of B8805-033 (3 μM), noradrenaline-induced contractions (pEC 50 6.55) were antagonized in a competitive manner by prazosin (p K B 9.24), tamsulosin (p K B 8.55), 2-(2,6-dimethoxyphenoxyethyl)aminomethyl-1,4-benzodioxane (WB 4101; p K B 7.81), spiperone (p K B 7.69), 4-amino-2-[4-[1-(benzyloxycarbonyl)-2( S)-[[(1,1-dimethylethyl)amino]carbonyl]-piperazinyl]-6,7-dimethoxyquinazoline (L-765,314; p K B 7.31), 5-methylurapidil (p K B 6.55), 8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione (BMY 7378; p K B 6.43), and 8-[2-(1,4-benzodioxan-2-ylmethylamino)ethyl]-8-azaspiro[4.5]decane-7,9-dione (MDL 73005EF; p K B 5.71), and were also antagonized by 100 μM chloroethylclonidine. N-[2-(2-cyclopropylmethoxyphenoxy)ethyl]-5-chloro-α,α-dimethyl-1 H-indole-3-ethanamine (RS-17053) behaved as a noncompetitive antagonist (apparent p A 2 6.55). Antagonist affinities obtained under these experimental conditions correlated highly with affinities at native and cloned α 1B-adrenoceptors. Pretreatment of arterial rings with B8805-033 (3 μM) followed by receptor inactivation with chloroethylclonidine (100 μM) yielded monophasic E/[ A] curves to noradrenaline (pEC 50 6.14). Noradrenaline-induced contractions were competitively antagonized by tamsulosin (p K B 10.32), 5-methylurapidil (p K B 8.66), RS-17053 (p K B 8.44), B8805-033 (p K B 7.87), BMY 7378 (p K B 6.54), and L-765,314 (p K B 6.41). Antagonist affinities obtained under these experimental conditions correlated highly with affinities at native and cloned α 1A-adrenoceptors. It is concluded that the contraction to noradrenaline in rat tail artery is mediated by both α 1B- and α 1A-adrenoceptors, each component of contraction being separable by use of selective α 1A-adrenoceptor blockade and α 1B-adrenoceptor alkylation, respectively.

Tetraethylammonium-evoked oscillatory contractions of rat tail artery: A K-K model

Spontaneously rhythmic contraction of peripheral blood vessels actively modulates the peripheral circulation and blood pressure. However, the underlying mechanisms for the complex rhythmic contraction patterns of various vascular tissues are not yet fully understood. In the present study, the tetraethylammonium (TEA)-induced spontaneously oscillatory contractions of isolated rat tail artery tissues were examined. It was found that TEA evoked arterial oscillatory contractions in a concentration-dependent, but endothelium-independent manner. The voltage-dependent K+ (Kv) channel specific blocker, 4-aminopyridine (4-AP), induced a sustained, but not oscillated, vascular contraction. The presence of 4-AP had no effect on the TEA-induced oscillatory contractions. The blockade of KCa channels with charybdotoxin or apamin did not affect the basal force of vascular tissues. Neither the TEA-induced oscillatory contraction was affected by these blockers. The opening of KATP channels by levcromakalim or their blockade by glybenclamide ceased or increased, respectively, the oscillation of TEA-induced contractions. The absence of Ca2+ or the presence of nifedipine in the bath solution completely abolished the effects of TEA. The inhibition of Ca2+-ATPase in the sarcoplasmic reticulum with micromolar concentrations of thapsigargin or cyclopiazonic acid either abolished or enhanced, respectively, the TEA-induced oscillatory contractions. Ryanodine did not affect the TEA-induced oscillatory contraction. In conclusion, the TEA-induced oscillatory contraction may be initiated by the blockade of the TEA-sensitive delayed rectifier K+ channels and maintained by the TEA-insensitive but ATP-sensitive K+ channels. This K-K model presents a novel mechanism for the depolarization-induced rhythmic contractions of small arteries.

Tetraethylammonium-evoked oscillatory contractions of rat tail artery: A K-K model

Tetraethylammonium-evoked oscillatory contractions of rat tail artery: A K-K model

Endogenous ATP Released by Electrical Field Stimulation Causes Contraction via P2x- and P2y-Purinoceptors in the Isolated Tail Artery of Rats

Electrical field stimulation (EFS) caused contraction of isolated tail arteries of rats. The EFS-induced contraction showed frequency-dependence and was entirely abolished by the sodium channel blocker tetrodotoxin (1 x 10(-7) M). The EFS-induced (at 20 Hz) contraction was reduced by about 60% in the presence of phentolamine (1 x 10(-6) M). Therefore, later experiments were carried out in the presence of phentolamine. Pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) (1 x 10(-8)-1 x 10(-6) M) and basilen blue E-3G (3 x 10(-5)-5 x 10(-5) M), P2-receptor antagonists, significantly inhibited the contraction evoked by EFS. In addition, PPADS significantly inhibited the contractions induced by ATP (1 x 10(-4) M) and a selective P2x-receptor agonist, alpha,beta-methylene ATP (1 x 10(-6) M). In contrast, basilen blue E-3G did not inhibit alpha,beta-methylene ATP-induced contraction. The ecto-ATPase activator apyrase (5 and 10 U/ml) significantly reduced the EFS-induced contractions. These findings suggest that endogenous ATP released by EFS causes contractions of rat tail artery via both the P2x-receptors and P2y-receptors.

Endogenous ATP released by electrical field stimulation causes contraction via P2x- and P2y-purinoceptors in the isolated tail artery of rats.

Electrical field stimulation (EFS) caused contraction of isolated tail arteries of rats. The EFS-induced contraction showed frequency-dependence and was entirely abolished by the sodium channel blocker tetrodotoxin (1 x 10(-7) M). The EFS-induced (at 20 Hz) contraction was reduced by about 60% in the presence of phentolamine (1 x 10(-6) M). Therefore, later experiments were carried out in the presence of phentolamine. Pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) (1 x 10(-8)-1 x 10(-6) M) and basilen blue E-3G (3 x 10(-5)-5 x 10(-5) M), P2-receptor antagonists, significantly inhibited the contraction evoked by EFS. In addition, PPADS significantly inhibited the contractions induced by ATP (1 x 10(-4) M) and a selective P2x-receptor agonist, alpha,beta-methylene ATP (1 x 10(-6) M). In contrast, basilen blue E-3G did not inhibit alpha,beta-methylene ATP-induced contraction. The ecto-ATPase activator apyrase (5 and 10 U/ml) significantly reduced the EFS-induced contractions. These findings suggest that endogenous ATP released by EFS causes contractions of rat tail artery via both the P2x-receptors and P2y-receptors.

Sources of calcium and alpha 1-adrenoceptor-mediated contraction in rat tail artery.

1. The relative importance of intracellular and extracellular Ca2+ on alpha 1-adrenoceptor-mediated contraction by noradrenaline and St-587 has been studied and correlated with the binding characteristics in intact tail artery from Sprague-Dawley rats. 2. Noradrenaline and St-587 behaved as full agonists inducing a concentration-dependent vasoconstriction. 3. Nifedipine (1 microM and 10 microM) blocked by 50% (P < 0.001) and 75% (P < 0.001) respectively, the maximum contraction (Emax) induced by St-587. Nevertheless, to reach 40% inhibition of Emax on noradrenaline responses (P < 0.01), 10 microM nifedipine was necessary. 4. Both agonists induced a concentration-dependent accumulation of inositol phosphates. Noradrenaline behaved as a full agonist and St-587 as a partial agonist for this response. 5. [3H]-prazosin binding to intact tail artery rings was saturable and of high affinity (KD = 4.44 +/- 0.46 nM; Bmax = 36.35 +/- 4.22 fmol mg-1 tissue). 6. Competition curves for inhibition of specific [3H]-prazosin binding by WB-4101 suggest that the rat tail artery contains two alpha 1-adrenoceptor subtypes in an approximate ratio of 60:40. 7. After irreversible alkylation of alpha 1B-adrenoceptors with 100 microM chloroethylclonidine (CEC), nifedipine (1 microM) influenced to a greater extent the St-587- than the noradrenaline-induced contraction. 8. Our results indicate that the degree of participation of intracellular and extracellular Ca2+ sources, on the alpha 1-adrenoceptor-mediated contraction, depends on the agonist used. The two alpha 1-adrenoceptor subtypes observed in binding experiments seem to be unrelated to the Ca2+ sources used for contraction.

Neuropeptide y potentiates norepinephrine-stimulated inositol phosphate production in the rat tail artery

We have recently demonstrated the ability of neuropeptide Y to augment norepinephrine-sti,ulated contractions of rat tail artery. In [ 3H]myo- inositol labeled segments of rat tail artery, addition of a concentration of neuropeptide Y (10 −8 M) known to potentiate contractile responses produced no effect on the basal accumulation of [ 3H]inositol phosphates. Addition of norepinephrine (10 −7 M), however, resulted in the rapid accumulation of [ 3H]inositol 1,4,5-trisphosphate to 325 ± 29 % of basal levels within 5 min. This effect of norepinephrine on [ 3H]inositol 1,4,5-trisphosphate accumulation was mirrored by significant increases (274 ± 25 % of control) in total [ 3H]inositol phosphates. When neuropeptide Y and norepinephrine were added together, the norepinephrine-stimulated increase in [ 3H]inositol 1,4,5-trisphosphate was significantly augmented (467 ± 35 % of control) as was the increase measured in total [ 3H]inositol phosphates (366 ± 21 % of control). We suggest that the ability of neuropeptide Y to augment norepinephrine-induced contraction of the rat tail artery is due, at least in part, to the ability of neuropeptide Y to increase norepinephrine-stimulated phospholipase C activity in vascular smooth muscle and may represent the mechanism of action of this co-neurotransmitter in vivo.

Frequency- and train length-dependent variation in the roles of postjunctional alpha 1- and alpha 2-adrenoceptors for the field stimulation-induced neurogenic contraction of rat tail artery.

The present paper examines the roles of postjunctional alpha 1- and alpha 2-adrenoceptors for the noradrenaline (NA)-induced neurogenic contractile response to field stimulation mainly with 1-100 pulses at 2 or 20 Hz, in the tail artery of adult normotensive rats. Pharmacological tools were employed to isolate and characterize the alpha 1- and alpha 2-adrenoceptor-mediated components of this response. The degree to which the drugs influenced NA release or reuptake was assessed by their effects on the electrochemically determined, stimulation-induced rise in the NA concentration at the innervated outer surface of the media. This response was unaffected by alpha,beta-methylene ATP (10 microM) or suramin (500 microM), added to desensitize or block P2-purinoceptors, respectively prazosin (0.1 microM) or SK&F 104078 (6-chloro-9-[(3-methyl-2-butenyl)oxyl]-3-methyl- 1H-2,3,4,5-tetrohydro-3-benzazepine, 0.1 microM), used to block postjunctional alpha 1- and alpha 2-adrenoceptors respectively, nifedipine (10 microM), blocker of Ca2+ influx through L-type channels, and ryanodine (10 microM), which blocks mobilization of Ca2+ from intracellular stores; it was moderately enhanced by yohimbine (0.1 microM), blocker of pre- and postjunctional alpha 2-adrenoceptors, and strongly enhanced by cocaine (3 microM) or desipramine (1 microM), blockers of NA reuptake. Judging from their inhibitory effects on the contractile responses to the alpha 1- and alpha 2-adrenoceptor agonists, phenylephrine and xylazine, prazosin (0.1 microM) and SK&F 104078 (0.1 microM) could be used to selectively block alpha 1- and alpha 2-adrenoceptors respectively, while yohimbine (0.1 microM) was less selective, strongly depressing alpha 2- and slightly depressing alpha 1-adrenoceptor-mediated responses. The alpha 1-adrenoceptor-mediated component of the contractile response to short trains at 20 Hz was fast in onset, brief in duration and abolished by ryanodine; that mediated by alpha 2-adrenoceptors was more delayed, prolonged and insensitive to ryanodine. Both components were dose-dependently depressed by nifedipine (0.1-10 microM). The small contractile responses to single pulses, or up to 50 pulses at 2 Hz, or short train (< 4 pulses) at 20 Hz, were more markedly depressed by 0.1 microM yohimbine or SK&F 104078 than by 0.1 microM prazosin and, hence, mediated mainly by alpha 2-adrenoceptors. The reverse was true of the much larger response to longer trains at 20 Hz, which thus probably was mediated mainly by alpha 1-adrenoceptors.(ABSTRACT TRUNCATED AT 400 WORDS)

New antagonists of the vasopressin receptor mediated contraction in rat tail artery

A perfused isolated rat tail artery preparation was employed to study antagonistic properties of four newly synthesized arginine-vasopressin (AVP) analogues against the V 1 receptor. The activity of the agents SCATyr(Me)AVP, OCATyr(Me)AVP, OCAAVP and SCAAVP was related to that of a recognized antagonist d(CH 2) 5Tyr(Me)AVP. SCATyr(Me)AVP elicited outstanding antagonistic properties by blocking at concentration of 10 −7 m nearly completely the constrictory activity of AVP. At concentration of 10 −9 m the agent inhibited the AVP-induced constriction of artery about 40 times more effectively than the oxytocin (OXT)-induced constriction. The results obtained prove the validity of the structure-activity relationship based search for new potent V 1 receptor antagonists.

Studies on the chemical modification of monensin. IV. Synthesis, sodium ion permeability, and biological activity of 7-O-acyl- and 7-O-alkylmonensins.

7-O-Acyl-(4a-e) and 7-O-alkylmonensins (5a-d) were prepared from monensin (1). Their lipophilicity, sodium ion permeability in human erythrocytes, antibacterial activity and effect on rat tail artery were examined. There was a correlation between lipophilicity and sodium ion permeability as well as between lipophilicity and antibacterial activity. We also found that the compound having larger sodium ion permeability, showed stronger contraction of rat tail artery. 7-O-Benzylmonensin (5c) exhibited higher lipophilicity and larger sodium ion permeability than monensin (1) among the tested monensin derivatives. In addition, antibacterial activity and contractile effect on rat tail artery of 5c were comparable to those of 1.

An amplifying effect of exogenous and neurally stored 5‐hydroxytryptamine on the neurogenic contraction in rat tail artery

1. The interactions between sympathetic neuroeffector transmission and 5-hydroxytryptamine (5-HT) were investigated in segments of rat isolated tail artery. 2. Contractile responses to field stimulation of the artery segments were abolished by tetrodotoxin (3 x 10(-7) M). A subthreshold concentration of acutely applied exogenous 5-HT (10(-8) M) markedly enhanced the contractions induced by sympathetic nerve stimulation, through an action on postjunctional 5-HT2-receptors. 3. The amplifying effect of 5-HT involved an enhanced influx of extracellular calcium into the smooth muscle cells. In contrast, the neurogenic contractions in vessels not exposed to 5-HT were not dependent on extracellular calcium. 4. The adrenergic component of the amplified response involved postjunctional alpha 1- but not alpha 2- adrenoceptor activation. 5. Exposure of the vessels to 5-HT (5 x 10(-7) M) for 30 min resulted in uptake of the amine into the perivascular sympathetic nerves, as demonstrated by immunohistochemistry. After chemical sympathectomy with 6-hydroxydopamine in vitro or in vivo, or surgical sympathectomy, there was little or no uptake. 6. Exposure to 5-HT followed by repeated washing resulted in an enhancement of the neurogenic contraction, which was still fully tetrodotoxin-sensitive. The enhanced response was blocked by ketanserin (10(-8) M) and prevented by the presence of the 5-HT uptake blocker, paroxetine (3 x 10(-8) M), during the period of exposure to 5-HT.

Ca 2+-dependence of endothelin-1 induced contraction of rat tail artery

1. 1. In rat tail artery, endothelin-1(ET-1) caused an increase in the cytosolic free Ca 2+ level ([Ca 2+] i) followed by a relatively sustained but not steady-state contraction in Ca 2+ containing solution. 2. 2. In the early phase of the contraction, the rate of increase in [Ca 2+] i was much faster than that in muscle tension. However, after the increases in [Ca 2+] i and muscle tension reached at their peaks, there was a good correlation between the changes of the two parameters. 3. 3. ET-1 could not induce an apparent contractile response in Ca 2+-free medium, notwithstanding it evoked a [Ca 2+] i transient in this medium. 4. 4. The results indicate that ET-1 induce a contraction of rat tail artery which is almost fully dependent on the [Ca 2+] i changes, and may inhibit the Ca 2+-sensitivity of the contractile filaments in the early phase of the contraction.

Potentiation by treatment with reserpine of α2-adrenoceptor-mediated contractions of rat tail artery

The effects of a treatment with reserpine on α-adrenoceptor-mediated contractile responses of rat tail arteries were investigated in vitro. The potency of norepinephrine was slightly increased in arteries obtained from rats treated with reserpine. There was no significant change in the sensitivity of the arteries to serotonin, KCl and selective α 1-adrenoceptor agonists (methoxamine and phenylephrine). However, the potency of clonidine and UK-14,304, both selective α 2-adrenoceptor agonists, was greatly increased. UK-14,304-induced contractions of the arteries from rats treated with reserpine were inhibited strongly by rauwolscine, a selective α 2-adrenoceptor antagonist, but only slightly by corynanthine, a selective α 1-adrenoceptor antagonist. The contractions caused by re-introduction of Ca 2+ during exposure to UK-14,304 but not to methoxamine in a Ca 2+-free medium were potentiated by treatment with reserpine. Bay K 8644, an agonist of Ca 2+ channels, produced a concentration-dependent contraction only in the arteries from rats treated with reserpine. These result suggest that treatment with reserpine potentials α 2- but not α 1-adrenoceptor-mediated responses in rat tail arteries and that the potential could be related to changes in mechanisms linked to Ca 2+ influx.