Rabbit Ear Artery Research Articles

Rabbit ear artery contraction to serotonin: ouabain-induced enhancement of response mediated by serotonergic instead of alpha adrenergic receptors

Rabbit ear artery contraction to serotonin: ouabain-induced enhancement of response mediated by serotonergic instead of alpha adrenergic receptors

Attenuation of long-lasting effects of sympathetic stimulation after repeated stimulation.

Neuropeptide Y (NPY) is stored with norepinephrine in sympathetic nerves throughout the cardiovascular system and is released during activation of the sympathetic nervous system in humans and other animals. After stimulation of the cardiac sympathetic nerves in anesthetized dogs, the action of the vagus nerve on heart rate is attenuated for a prolonged period. This attenuation of cardiac vagal action is also seen after injection of NPY. Both sympathetic stimulation and exogenous NPY inhibit cardiac vagal effects by acting on postganglionic vagal nerves. Because the supply of neuropeptides to nerve terminals is by axonal transport, it might be expected that repeated stimulation of cardiac sympathetic nerves would deplete the sympathetic neural factor, proposed to be NPY. In all 11 dogs of this study, repeated episodes of stimulating the cardiac sympathetic nerve (16 Hz for 1 minute each) had a diminishing effect in attenuating cardiac vagal action. However, the episodes of sympathetic stimulation did not show diminishing effectiveness in increasing heart rate. Exogenous NPY had similar inhibitory effects on vagal action whether given at the beginning or the end of the episodes of sympathetic stimulation. Transmural stimulation of sympathetic nerves around rabbit ear arteries produced effects that are also mimicked by NPY. These are prolonged potentiation of contractions evoked by injection of norepinephrine or by brief bursts of transmural stimulation. Repeated stimulations in this case also had diminishing abilities to evoke such potentiations. Both sets of observations are consistent with repeated stimulation of sympathetic nerves causing depletion of a nonadrenergic transmitter, possibly NPY.

The action of caffeine on inward barium current through voltage-dependent calcium channels in single rabbit ear artery cells

The effect of caffeine on inward current carried by barium ions through voltage-dependent calcium channels has been investigated in single rabbit ear artery cells using whole-cell voltage-clamp techniques. Caffeine (1-30 mM) caused a rapid and reversible concentration-dependent blockade of barium current and a related compound, 3-isobutyl-1-methylxanthine (IBMX), was a more potent inhibitor of barium current. Caffeine-induced inhibition of barium current showed no voltage- or use-dependence and caffeine did not alter the steady-state inactivation of barium current. The effect of caffeine was not blocked by extracellular or by intracellular ryanodine or inclusion of both 5 mM 1,2-bis(2-aminophenoxy)-ethane N,N,N',N',-tetraacetic acid (BAPTA) and 2 mM ethylene glycol-bis(beta-amino ethyl ether) N,N,N',N',-tetraacetic acid (EGTA) in the intracellular solution. Rolipram and M&B 22984, non-xanthine inhibitors of phosphodiesterase, did not diminish inward barium current. The data indicate that caffeine and IBMX block voltage-operated calcium channels and it is suggested that this is due to a direct interaction of methylxanthines with the calcium channel.

Potassium, chloride and non‐selective cation conductances opened by noradrenaline in rabbit ear artery cells.

1. The action of noradrenaline on cells isolated from the rabbit ear artery was studied with the whole-cell configuration of the patch clamp technique. In normal potassium-containing solutions at a holding potential of -50 mV noradrenaline elicited either outward, inward or mixed outward and inward currents. These responses were blocked by the alpha-adrenoceptor antagonist, phentolamine (10(-6) M). 2. The outward current occurred as a consequence of an increase in membrane conductance and the reversal potential was close to the potassium equilibrium potential (EK). It was possible to record outward currents without external calcium but not when the concentration of EGTA in the pipette was increased to 10 mM or when potassium was absent from the pipette solution. It is concluded that the outward current evoked by alpha-adrenoceptor stimulation is produced by a calcium mediated increase in potassium conductance. 3. The ionic basis of the inward current was investigated in potassium-free external and pipette solutions. When sodium chloride was the major constituent of the external and pipette solutions the reversal potential (Er) of the noradrenaline-induced current was 0.63 mV, close to ENa and ECl. 4. When most of the external sodium chloride was replaced by sucrose Er was intermediate between ENa and ECl but had shifted significantly towards ENa. Further ion substitution experiments suggest that noradrenaline increased the membrane conductance to both anions and cations. 5. When the current was carried predominantly by anions, depolarizing steps (from -50 mV) produced outward current relaxations with a time constant of about 40 ms. Bath-applied caffeine also produced a membrane current which rectified in the outward direction. 6. When the response to noradrenaline was mediated mainly by cations, the relationship between the membrane current and clamp potential was non-linear and the amplitude of the currents at potentials positive to -50 mV became disproportionately smaller. In addition on repolarization to -50 mV the instantaneous current was followed by an inward relaxation. 7. In high external barium solution noradrenaline evoked a membrane current with a reversal potential much more positive than ENa or ECl. This current was recorded in the presence of 10(-5) M-nifedipine and diltiazem and in 10(-4) M-cadmium which suggests that the voltage-dependent calcium channel is not implicated in the generation of the non-selective cation current to noradrenaline.(ABSTRACT TRUNCATED AT 400 WORDS)

Lacidipine

Lacidipine, currently being evaluated as a once-daily antihypertensive agent, acted as a calcium entry blocker on rabbit ear artery (pA2 = 9.4) with a markedly slower onset of action than that of nitrendipine; this effect was not reversed after 9 h of drug washout. Calcium entry blocker activity was also evaluated on nonvascular smooth muscles: Lacidipine showed a more pronounced vascular selectivity than nitrendipine; for both drugs, concentrations required to induce negative inotropic effects in guinea pig ventricular strip were approximately 100 times higher than concentrations needed to antagonize calcium contraction in vascular smooth muscle. In spontaneously hypertensive rats (SHR), by the tail-cuff method, lacidipine (ED25 = 0.35 mg/kg orally, p.o.) proved approximately 30 times more potent, slower in onset, and longer-acting than nitrendipine in reducing blood pressure. These features were confirmed in chronically implanted SHR after oral and intravenous (i.v.) administration (ED25 = 0.19 mg/kg p.o. and 0.006 mg/kg i.v.). A short-lasting tachycardia was detected with both drugs. No evidence of acquired tolerance emerged after repeated oral administrations over a 3-week period. Lacidipine induced a natriuretic effect in saline-loaded SHR at antihypertensive doses. In renal hypertensive dogs, lacidipine proved more potent (three to seven times), slower in onset, and longer-lasting than nitrendipine after p.o. (ED25 = 0.22 mg/kg) and i.v. (ED25 = 0.004 mg/kg) administrations.

Washout of Vessels with Heparin Does Not Improve Patency Following Severe Microarterial Trauma: An Experimental Study

The antithrombotic effect of heparin used as a wash-out solution in small arteries has been evaluated following severe vessel trauma (arteriotomy/intimectomy). Twenty-three central arteries of rabbit ears were prepared and platelets labeled with phosphorus-32 injected intraaortically. The arteries were positioned in double vascular clamps and opened by arteriotomy, and intimectomy was performed. After reestablishing blood flow, arteriotomic bleeding times, platelet accumulation in vivo, patency, and the amounts of intraluminal red thrombotic material were recorded. The rabbits were divided into two groups. In group A (12 vessels) the vessel interior was flushed with 2 ml of saline or Ringer's lactate solution. Group B (11 vessels) was similar except that the vessels were flushed with 2 ml of heparin, 100 IU/ml, in Ringer's lactate solution. In the control group (A) the bleeding time was 5 +/- 2 min, while in group B bleeding was so profuse that extra sutures had to be used in 6 of the vessels. Although significantly fewer platelets accumulated in heparin-treated animals, the patency frequencies and amounts of thrombotic material observed in both groups were similar. The final volume of thrombus formed is thus not always proportional to the degree of platelet accumulation. Washout of small traumatized arteries with heparin is thus not beneficial.

Flow-induced resistance artery tone: balance between constrictor and dilator mechanisms

Infusion of physiological saline solution into the lumen of an isolated segment of a resistance artery results in constriction when the vessel is relaxed and in dilation when it is contracted. There is a level of wall tone at which infusion causes no change. In the small rabbit ear arteries used in this study (approximately 200 microns OD) this balance (null) point for infusion rates of 35 microliters/min is 69 +/- 4% of the maximum possible tone development. When tone is set at different levels by norepinephrine, infusion tends to change the level of wall force in the direction of the null point for that artery. The magnitude of flow-induced relaxation can be correlated positively (r = 0.74; P less than 0.001) and the flow-induced constriction correlated negatively (r = -0.67; P less than 0.001) with the level of wall tone. The 95% confidence prediction bands for flow relaxation and contraction against level of wall tone overlap when extrapolated to zero response. These results are consistent with the hypothesis that flow-induced change in resistance artery tone is the result of a balance between independent constrictor and dilator influences.

Low volume perfusion-superfusion system for measurement of transmitter release from blood vessels in vitro

An in vitro technique has been developed for the simultaneous recording of vasoconstriction and transmitter release from small perfused blood vessels. To avoid excessive dilution of the released substances, 6–12-mg segments of rabbit ear arteries or rat tail arteries were mounted in 0.5-mL tissue chambers and perfusedsuperfused in a closed system. Drug administration and removal were performed by timer-controlled solenoid valves. Oscillation in the baseline generated by the roller pump was dampened by delivering Krebs' solution through a 4-mL buffer vial filled partly with air. Vasoconstriction was elicited by electrical stimulation and detected by pressure sensitive transducers. Transducer-generated electrical signals were amplified, digitalized, and recorded by a computerized system. Release of norepinephrine was measured after the tissue was preloaded with [ 3H]norepinephrine. This system allowed us to measure minimum vasoconstrictions of 1–2 mm Hgand [ 3H]norepinephrine efflux evoked by 4–8 electrical pulses. There was a good linear correlation ( r = 0.98) between the contractile responses and tritiated norepinephrine release. Endogenous norepinephrine released by electrical stimulation into the perfusion media was determined by high-performance liquid chromatography (HPLC) in the low picogram range (80–100 pg). Our novel experimental setup permits computerized data acquisition and automated in vitro pharmacological experiments on isolated blood vessels.

Neuropeptide Y potentiates purinergic as well as adrenergic responses of the rabbit ear artery

The localisation of neuropeptide Y in the rabbit central ear artery and its pharmacological action on this preparation were investigated. Immunohistochemical studies demonstrated the presence of neuropeptide Y-like immunoreactivity in the perivascular nerves supplying the rabbit ear artery. Forty-eight hours after treatment with reserpine (5 mg/kg i.p. 48 h and 3 mg/kg i.p. 24 h prior to the experiment) catecholamine fluorescence in the rabbit central ear artery was abolished and the neuropeptide Y-like immunoreactivity was substantially reduced, suggesting that noradrenaline and neuropeptide Y were colocalised in sympathetic nerves. Contractile responses to exogenous noradrenaline (1 μM) and α,β-methylene ATP (1 μM) were both significantly potentiated following incubation with neuropeptide Y (0.3 μM); the degree of potentiation being similar for both agonists. Electrical field stimulation of the rabbit central ear artery (16 and 64 Hz) produced frequency-dependent contractile responses which were abolished by tetrodotoxin (1 μM) and which were significantly potentiated in the presence of neuropeptide Y (0.3 μM). The responses to stimulation at 16 Hz were enhanced to a greater extent than the responses at 64 Hz. After blocking the noradrenergic component of the neurogenic response with prazosin (1 μM), the residual purinergic component, at both 16 and 64 Hz, was significantly enhanced in the presence of neuropeptide Y. However, following desensitisation of the P 2-purinoceptor with α,β-methylene ATP, neuropeptide Y had no significant effect on the residual noradrenergic component. The results from this study show that neuropeptide Y has a postjunctional modulatory action on the responses elicited by electrical stimulation of the perivascular nerves in the presence and absence of prazosin as well as on the responses to the exogenously applied cotransmitters noradrenline and ATP.

Effect of lipoxygenase inhibitors on Ca 2+-induced constriction of the rabbit ear artery

1. 1. The effects of nafazatrom, nordihydroguaiaretic acid (NDGA) and quercetin on Ca 2+-induced vasoconstriction were studied in isolated rabbit ear arteries. 2. 2. The arteries were perfused with Ca 2+-free and high K + (75 mM) Krebs bicarbonate buffer. Constriction of the artery was induced by addition of Ca 2+ (1.5 mM) to the perfusion fluid. 3. 3. Indomethacin (1 μM) did not alter the response to Ca 2+. 4. 4. Nafazatrom (2 or 5 μM) produced a concentration-dependent inhibition of the constrictor response to Ca 2+ ranging from 4 to 23% after 1 hr of perfusion and 26 to 62% after 3 hr. 5. 5. Similar effects were obtained with NDGA and quercetin (0.5 and 1 μM). 6. 6. The inhibitory effects of nafazatrom and quercetin were antagonized by Ca 2+ (2.5 mM) or Bay K 8644 (1 μM), a calcium channel activator. 7. 7. Ca 2+-induced contractions recovered within 30 min after discontinuation of perfusion with quercetin, whereas nafazatrom and NDGA had longer durations of action. 8. 8. These results suggest that inhibitors of lipoxygenase antagonized Ca 2+-induced vasoconstriction and that products of lipoxygenase metabolism may facilitate Ca 2+ entry into vascular smooth muscle cells.

The Influence of Body Temperature on Traumatic Vasospasm

The effect of hypothermia on traumatically induced vasospasm was studied in an in vivo model of the rabbit ear artery. Spasm was induced by standardized compression of a 3.2 mm segment of the artery for 3 s. The internal diameter was continuously measured with the aid of an operating microscope during transillumination of the artery. Measurements were begun before spasm induction and continued until the spasm was completely resolved. Spasm was first induced at normothermia and then after reduction of the body temperature by 1.0 degrees C and 1.75 degrees C. The spasm was evaluated in terms of its duration, intensity (% reduction of initial diameter) and severity (area under the curve where diameter was plotted against time). The results were compared with those in a control group which was kept normothermic. Reduction of the body temperature caused a significant increase in the duration of the spasm and increased its severity, but did not influence its intensity.

Time of low‐dose acetylsalicylic acid administration influences in vivo platelet function and thrombus formation following arteriotomy and intimectomy; an experimental study in small arteries of Rabbits

To investigate if low-dose acetylsalicylic acid (ASA), 4 mg/kg b.w., infused peroperatively or 10 hours preoperatively has antithrombotic effects, the central arteries of rabbit ears were prepared and 32P-labeled platelets injected. Arteriotomy and intimectomy were performed and blood flow was restored. Bleeding times at the sites of arteriotomy/intimectomy, in vivo accumulations of isotope-labeled platelets, amounts of red thrombotic material, and patency were recorded. Bleeding times following arterial puncture and the effect of ASA on thromboxane production were studied separately. Ten hours after ASA administration, bleeding times were shortened at the sites of arteriotomy/intimectomy but were prolonged following arterial puncture. Platelet accumulations were lower in patent vessels in this group than in an untreated control group. Peroperative ASA treatment increased but treatment 10 hours prior to blood flow restoration did not significantly affect the number of occlusions. Thromboxane production in ASA-treated rabbits is largely inhibited even 14 hours after administration.

Dual effects of capsaicin on responses of the rabbit ear artery to field stimulation

1. The effects of capsaicin (Cap) on contractions of ring segments of rabbit ear artery induced by field stimulation were studied. 2. At low concentrations (0.3-3 microM) Cap caused transient enhancement and at higher concentrations (above 3 microM) inhibition of stimulation-induced contractions, without affecting noradrenaline (NA)-induced contractions. 3. In the continuous presence of high concentrations of Cap, rebound facilitation was observed after inhibition, and at this stage, Cap elicited less inhibition of the response. 4. Repeated application of Cap at 60 min intervals irreversibly desensitized the artery to the inhibitory effect of Cap. 5. Functional removal of the endothelium enhanced the facilitatory effect of low concentrations of Cap and attenuated its inhibitory effect. 6. Pretreatment with indomethacin abolished the facilitatory effect of Cap and enhanced its inhibitory effect, indicating that prostaglandins are involved in the action of Cap. The effect of indomethacin was more marked in preparations from which the endothelium had been removed. 7. Desensitization to substance P (SP) or substance K (SK), did not affect either the inhibitory or the facilitatory effect of Cap. 8. These results suggest that the dual effects of Cap on stimulation-induced contractions of rabbit ear artery may arise from the release of multiple mediators that act prejunctionally to modulate NA release. The stimulant effect seems to be mediated by prostanoids, while the inhibitory effect seems to be caused by a substance(s) that is not SP or SK. The possibility that the mediator is calcitonin gene-related peptide requires further study.

ATP‐activated channels gate calcium entry in single smooth muscle cells dissociated from rabbit ear artery.

1. A combination of the techniques of microspectrofluorimetry and whole-cell patch clamp was used to investigate changes in cytoplasmic Ca2+ concentration (Cai2+) in single arterial smooth muscle cells on external application of ATP. 2. ATP applied to cells held under voltage clamp at --60 mV evoked an inward current and an associated rise in Cai2+. In the absence of extracellular Ca2+. ATP-activated inward currents were observed but there was no rise in Cai2+. 3. Pre-treatment of cells with noradrenaline or caffeine did not prevent the rise in Cai2+ on subsequent application of ATP. 4. The ATP-activated rise in Cai2+ was voltage dependent as outward currents evoked by ATP at positive membrane potentials were not associated with a change in Cai2+. 5. At --60 mV, the rise in Cai2+ due to ATP application was dependent on the magnitude of the ATP current response, such that Cai2+ increased by about 0.5 nM/pC charge transferred through ATP-gated channels. 6. The results suggest that ATP-gated channels in these cells admit sufficient Ca2+ in a physiological Ca2+ gradient to significantly elevate Cai2+. About 10% of the ATP-gated current may be carried by Ca2+ ions. Thus the ATP-activated channels have a dual excitatory function: depolarization due to Na+ entry promotes action potential discharge and voltage-gated Ca2+ entry, and also direct entry of Ca2+ through the ATP-activated channels.

Neurogenically mediated contractions of dog basilar artery involve the release of a thromboxane-like substance

Electrical field stimulation of dog isolated basilar artery produced neurogenically mediated contractions which were unaffected by phentolamine (1 μM), atropine (1 μM), ketanserin (1 μM) or methiothepin (0.1 μM). Responses were abolished by GR32191 (1–10 nM), BM 13.177 (0.1–10 μM) or flurbiprofen (0.5 μM) and markedly attenuated by dazoxiben (1–10 μM). Removal of the endothelium by Triton X-100-perfusion did not modify the magnitude of contractions to electrical stimulation and GR32191 still abolished the responses. GR32191 (1–10 nM) did not modify neurogenically mediated contraction of rabbit ear artery or potassium chloride-induced contraction of dog basilar artery. The results suggest that electrical field stimulation of dog basilar artery causes contractions which are mediated via a cyclo-oxygenase product with characteristics similar to thromboxane. This thromboxane-like substance is not endothelial in origin, nor released by contraction of the cerebrovascular smooth muscle per se and is therefore derived from a subendothelial, possibly neuronal, source.

SK&F 89124, a potent and selective agonist at prejunctional dopamine receptors.

SK&F 89124 (4-[2-(N,N-di-n-propylamino)ethyl]-7-hydroxy-2(3H) indolone) can be considered as a derivative of N,N-di-n-propyldopamine (DPDA) in which the meta-hydroxyl is replaced by a cyclic amide function. SK&F 89124 is at least one order of magnitude more potent than DPDA as an agonist at peripheral inhibitory prejunctional dopamine receptors (DA2 receptors) in the isolated perfused rabbit ear artery. A potent agonist action of SK&F 89124 at the DA2 receptor can also be demonstrated by inhibition of radioactive overflow from prelabelled canine coronary artery or saphenous vein, and in the anesthetized dog as an inhibition of the tachycardia induced by cardioaccelerator nerve stimulation or the increase in hind-limb perfusion pressure induced by stimulation of the lumbar sympathetic chain. SK&F 89124 is a potent inhibitor of the binding of [3H]spiroperidol to D2 receptors in bovine pituitary homogenates. High concentrations of SK&F 89124 do not activate the adenylate cyclase D1 receptor in rat caudate homogenates, nor produce activation of alpha 2-adrenoceptors or H2-histamine receptors in the guinea pig atrium. Although some alpha 1-adrenoceptor mediated vasoconstriction is produced in the rabbit ear artery and rabbit aorta, the concentrations required are several orders of magnitude higher than those active at the DA2 receptor. From these data it is evident that this structural modification can increase both the potency and selectivity of DPDA as a DA2 receptor agonist. The potency and selectivity of SK&F 89124 make this agent a useful tool for determination of the functional role of the DA2 receptor.

Pharmacology of a potent, new antithrombotic agent, 1,3-dihydro-7,8-dimethyl-2 [formula omitted]-imidazo[4,5- [formula omitted]]quinolin-2-one (BMY-20844)

The effects of 1,3-dihydro-7,8-dimethyl-2 H -imidazo[4,5- b ]quinolin-2-one (BMY-20844) on platelet function and experimental thrombosis were evaluated in a series of in vitro , ex vivo and in vivo experiments. The compound inhibited platelet aggregation in vitro in platelet rich plasma obtained from humans, rats and rabbits with EC sos of less than 1 μg/ml when aggregation was induced by ADP, collagen or thrombin. Supra-additive interaction against ADP aggregation was also observed when BMY-20844 was combined with prostacyclin. BMY-20844 was orally active with an ex vivo ED 50 in the rat of 3.2 mg/ kg vs ADP. Significant antithrombotic activity was observed in two animal models (laser induced thrombosis in the microcirculation of the rabbit ear and coronary artery thrombosis in the dog). Inhibitions of 52% at 3 mg/kg p.o. in the laser model and 100% at 1 mg/kg i.d. in the coronary artery thrombosis model were obtained. Modest inotropic and hemodynamic effects were observed in ferrets and dogs. BMY-20844 was found to be a potent, specific inhibitor of platelet low Km cyclic AMP phosphodiesterase.

Endothelium removal does not affect potentiation by neuropeptide Y in rabbit ear artery

Influence of endothelial cells on the effect of neuropeptide Y (NPY) was investigated. NPY (30 nM) doubled the vasoconstriction elicited by transmural nerve stimulation (8 pulses at 8 Hz) in the perfused rabbit ear artery with or without endothelium. Conditions that increase the biophase concentration of norepinephrine, longer stimulation trains or application of yohimbine, decreased the potentiation by NPY, although in the presence of cocaine potentiation by NPY was unchanged. However, no significant differences between control and endothelium-removed arteries were revealed. Thus modulation of adrenergic neurotransmission by NPY does not depend on endothelium-derived vasoactive substances.

Characterization of 5-hydroxytryptamine receptors in the cranial vasculature

The availability of selective compounds has made it possible to subdivide 5-hydroxytryptamine (5-HT) receptors into three distinct types, called 5-HT1-like, 5-HT2 and 5-HT3. The selective agonists at the three receptor types are, respectively, 5-carboxamidotryptamine, alpha-methyl-5-HT and 2-methyl-5-HT. While no selective antagonists are yet available for the 5-HT1-like receptors, some compounds, including ketanserin and MDL 72222, selectively antagonize 5-HT2 and 5-HT3 receptors respectively. Depending upon experimental conditions, 5-HT causes a constriction or dilatation of cerebral and extracerebral cranial vessels. Vascular contraction by 5-HT seems to be mediated primarily via 5-HT2 receptors (located mainly on large conducting vessels), though in several instances (for example, dog and human basilar arteries and porcine arteriovenous anastomoses; AVAs) 5-HT1-like receptors are involved in addition to or in place of 5-HT2 receptors. In the rabbit ear and external carotid arteries 5-HT may act directly on alpha-adrenoceptors. Arteriolar dilatation, leading to increased capillary ("nutrient") blood flow, occurs via 5-HT1-like receptors. However, the 5-HT1-like receptors on the arterioles and AVAs appear to be similar but not identical. Since a reduction of plasma 5-HT and opening of AVAs have been implicated in the pathophysiology of migraine, compounds acting on 5-HT1-like receptors to close the shunt vessels can be expected to have therapeutic activity in migraine.

AlF 4 ? inhibits the accumulation of Ca in the endoplasmic reticulum in intact myometrial strips, but not in the rabbit ear artery

AlF-4, known to be a potent modulator of G-proteins, also inhibits purified "P"-type cation-transport ATPases (Missiaen et al. 1988). The aim of the present work is to find out whether AlF-4 also inhibits these ATPases in intact cells. We therefore have studied the effect of AlF-4 on the force development and on 45Ca2+ -fluxes of muscle strips from rat myometrium and rabbit ear artery. 1 mM-NaF plus 10 microM-AlCl3 induces in both tissues a tonic contraction that is completely blocked by 0.5 mM-deferoxamine. The contractile response in myometrium exceeds that of the ear artery. These contractions are independent of an activation of G-proteins but their amplitude depends on [Ca2+]o. Application of AlF-4 during the loading of the endoplasmic reticulum of myometrium with Ca2+ dramatically reduces the amount of stored Ca2+ as estimated from its release induced by 1 mM-carbachol during incubation in Ca-free solution. This effect could be due to a predominant inhibitory effect of AlF-4 on the (Ca2+ + Mg2+)-ATPase of the endoplasmic reticulum. Such effect could not be established in rabbit ear artery. The increase of the fractional loss of 45Ca2+ induced by 10 microM-norepinephrine in rabbit ear artery is not inhibited by AlF-4. It is concluded that the inhibition of the endoplasmic-reticulum (Ca2+ + Mg2+)-ATPase in intact myometrial cells warns us against explaining all effects of AlF-4 on intact cells only by an activation of G-proteins.(ABSTRACT TRUNCATED AT 250 WORDS)