The impacts of different embolization techniques on splenic artery embolization for blunt splenic injury: a systematic review and meta-analysis.

BACKGROUND: Splenic artery embolization (SAE) has been an effective adjunct to the Non-operative management (NOM) for blunt splenic injury (BSI). However, the optimal embolization techniques are still inconclusive. To further understand the roles of different embolization locations and embolic materials in SAE, we conducted this system review and meta-analyses. METHODS: Clinical studies related to SAE for adult patients were researched in electronic databases, included PubMed, Embase, ScienceDirect and Google Scholar Search (between October 1991 and March 2013), and relevant information was extracted. To eliminate the heterogeneity, a sensitivity analysis was conducted on two reduced study sets. Then, the pooled outcomes were compared and the quality assessments were performed using Newcastle-Ottawa Scale (NOS). The SAE success rate, incidences of life-threatening complications of different embolization techniques were compared by χ2 test in 1st study set. Associations between different embolization techniques and clinical outcomes were evaluated by fixed-effects model in 2nd study set. RESULTS: Twenty-three studies were included in 1st study set. And then, 13 of them were excluded, because lack of the necessary details of SAE. The remaining 10 studies comprised 2nd study set, and quality assessments were performed using NOS. In 1st set, the primary success rate is 90.1% and the incidence of life-threatening complications is 20.4%, though the cases which required surgical intervention are very few (6.4%). For different embolization locations, there was no obvious association between primary success rate and embolization location in both 1st and 2nd study sets (P > 0.05). But in 2nd study set, it indicated that proximal embolization reduced severe complications and complications needed surgical management. As for the embolic materials, the success rate between coil and gelfoam is not significant. However, coil is associated with a lower risk of life-threatening complications, as well as less complications requiring surgical management. CONCLUSIONS: Different embolization techniques affect the clinical outcomes of SAE. The proximal embolization is the best option due to the less life-threatening complications. For commonly embolic material, coil is superior to gelfoam for fewer severe complications and less further surgery management.

Proximal Splenic Artery Embolization in Chemotherapy-Induced Thrombocytopenia: A Retrospective Analysis of 13 Patients.

PURPOSE: To determine if proximal splenic artery embolization (PSAE) provides a safe and effective alternative to alleviate chemotherapy-induced thrombocytopenia (CIT), allowing patients with cancer to resume chemotherapy regimens. MATERIALS AND METHODS: Thirteen patients (9 men, 4 women; mean age, 63 y) with underlying malignancy (pancreatic adenocarcinoma, n = 6; cholangiocarcinoma, n = 5; other, n = 2) complicated by CIT underwent PSAE. Mean platelet counts were calculated before the initiation of chemotherapy, at the nadir that resulted in discontinuation of chemotherapy before the PSAE procedure, at peak values after the procedure, and at a mean follow-up of 9.2 months. The time to reinitiation of chemotherapy after PSAE was calculated. RESULTS: Baseline platelet count before initiation of chemotherapy was 162 × 10(9)/L (range, 90-272 × 10(9)/L). The platelet count nadir resulting in cessation of chemotherapy was 45 × 10(9)/L (range, 23-67 × 10(9)/L), and the pre-PSAE platelet count was 88 × 10(9)/L (range, 49-131 × 10(9)/L). The post-PSAE peak platelet count improved significantly (to 209 × 10(9)/L; range, 83-363 × 10(9)/L) compared with the nadir counts and the pre-PSAE counts (P < .01) at a mean short-term follow-up of 35 days (range, 7-91 d). The counts at follow-up to 9.2 months (range, 3-15 mo) were 152 × 10(9)/L (range, 91-241 × 10(9)/L). All patients became eligible to resume chemotherapy. The time to initiation of chemotherapy after PSAE averaged 22 days (range, 4-58 d) in 12 patients; one patient declined chemotherapy. CONCLUSIONS: Proximal splenic artery embolization appears to be safe and effective in alleviating CIT, allowing resumption of systemic chemotherapy. Further studies may help guide patient selection by identifying characteristics that allow a sustained improvement in thrombocytopenia.

Spontaneous splenic infarction associated with sumatriptan use.

Triptans are specific agonists of the serotonergic 5-HT(1B/1D) receptors that have increasingly been used in the treatment of migraine and cluster headaches. Though they are generally considered safe, there have been a few reports of myocardial infarction and stroke associated with triptan use. We report a patient who developed spontaneous splenic infarction after the use of sumatriptan for the treatment of migraine headache.

Modification of transmitter release from periarterial nerve terminals by dipyridamole in canine isolated splenic artery.

1. The aim of the present study was to determine the modulatory effects of dipyridamole on purinergic and adrenergic transmission in the canine isolated, perfused splenic artery. 2. Periarterial nerve electrical stimulation readily induced a double-peaked vasoconstriction consisting of an initial transient, predominantly P2X receptor-mediated constriction followed by a prolonged, mainly alpha1-adrenoceptor-mediated response. 3. Exposure of tissues to dipyridamole (0.1-1 micro mol/L) dose-dependently inhibited both the first and second peaks of the vasoconstrictor response at a low frequency of stimulation (1 Hz), whereas at an intermediate frequency of stimulation (4 Hz), the first peak of the response was depressed without any significant effect being observed on the second peak of constriction. 4. At a higher dose (1 micro mol/L) dipyridamole potentiated vasoconstrictor responses to noradrenaline (0.03-1 nmol). At any doses used, dipyridamole had no effect on the vasoconstrictor responses to ATP (0.03-1 micro mol). 5. Tyramine (0.01-0.3 micro mol) induced vasoconstriction in a dose-dependent manner. The dose-response curves for tyramine were shifted to the right following treatment with dipyridamole (0.1-1 micro mol/L). 6. The present results indicate that dipyridamole may inhibit purinergic and adrenergic transmission presynaptically, whereas postsynaptically dipyridamole may potentiate the adrenergic vascular constriction by inhibition of transmitter uptake.

Neuroeffector mechanisms involved in the regulation of dog splenic arterial tone.

It has been recognized that sympathetic neurons release several transmitters but mainly adenosine 5'-triphosphate (ATP), noradrenaline, and neuropeptide Y (NPY). Recently, we reported that periarterial nerve electrical stimulation (PNS) produced biphasic vasoconstrictions consisting of an initial transient, predominantly P2X-purinoceptor-mediated constriction followed by a prolonged, alpha(1)-adrenoceptor-mediated one in canine isolated splenic arteries. In this article, we tried to analyze the effects of several selective key drugs that influence the PNS-induced responses, and we functionally showed sympathetic transmitter releasing mechanisms by pharmacological analysis using purinergic, adrenergic, and NPYergic agonists and antagonists.

Angiotensin II receptor subtypes involved in the modulation of purinergic and adrenergic vasoconstrictions to periarterial electrical nerve stimulation in the canine splenic artery.

Previous experiments demonstrated that periarterial electrical nerve stimulation induced a double-peaked vasoconstriction consisting of an initial transient, predominantly P2X-purinoceptor-mediated, constriction followed by a prolonged, mainly alpha1-adrenoceptor-mediated, response in the canine splenic artery. Angiotensin II at a concentration of 0.1 nM did not affect the basal vascular tone and vasoconstrictions to exogenously administered noradrenaline (0.03-3 nmol) and adenosine 5'-triphosphate (0.01-1 micromol), but it markedly potentiated the double-peaked responses to nerve stimulation. The potentiating effect of angiotensin II was inhibited by KRH-594 (10 nM), a selective angiotensin II type 1 receptor antagonist, but was not influenced by PD123319 (0.01-0.1 microM), a selective angiotensin II type 2 receptor antagonist. The results indicate that angiotensin II potentiates sympathetic purinergic and adrenergic vasoconstrictions through the prejunctional angiotensin II type 1 receptor subtype in the canine splenic artery.

Different sensitivities to alpha1 adrenoceptor blockade on periarterial sympathetic nerve-induced constriction by low and high frequencies in canine isolated splenic arteries.

The periarterial nerve electrical stimulation at 4 and 10 Hz induced a monophasic vasoconstriction of the canine splenic artery in a pulse number-related manner (1-30 pulses). The responses at 4 Hz were not significantly affected by 0.1 microM prazosin, but abolished by 1 microM alpha, beta-methylene ATP. Prazosin (0.1 microM) partially but significantly inhibited responses at 10 Hz, and the remaining responses were blocked by 1 microM alpha, beta-methylene ATP. It indicates that the monophasic vasoconstrictor response to short pulses of stimulation at a low frequency is mediated by P2X-receptors, whereas the response at a high frequency may be due to activation of not only P2X-receptors but also alpha1 adrenoceptors.

Neuropeptide Y inhibits double peaked vasoconstrictor responses to periarterial nerve stimulation primarily through prejunctional Y2 receptor subtype in canine splenic arteries.

1 The effects of BIIE 0246, a novel and non-peptide neuropeptide Y (NPY) Y2 receptor antagonist on sympathetic vasoconstriction of the canine splenic artery were investigated. 2 The vasoconstrictor response to periarterial electrical nerve stimulation was described to be a double peaked vasoconstriction consisting of an initial transient, dominantly P2X purinoceptor-mediated constriction followed by a prolonged, mainly alpha1 adrenoceptor-induced response. 3 BIIE 0246 at a concentration of 0.1-1 microM dose-dependently potentiated double peaked constrictions at low frequencies (1 and 4 Hz), whereas at high frequency (10 Hz), it failed to affect these responses. BIIE 0246 (1 microM) also enhanced double peaked responses even in the presence of rauwolscine (0.1 microM). NPY (13-36) (1-100 nM), a selective Y2 receptor agonist reduced these two peaked responses in a dose-related manner. The vasoconstriction to noradrenaline (0.1-10 nmol) or adenosine triphosphate (0.01-1 micromol) was not significantly influenced by either 1 microM BIIE 0246 or 100 nM NPY (13-36). Exposure of tissues to 1 microM BIIE 0246 almost completely prevented the suppression of double peaked constrictions by NPY (13-36) (10 nM) or by NPY (10 nM). 4 We conclude that NPY inhibits sympathetic purinergic and adrenergic vasoconstrictions through an activation of prejunctional Y2 receptor subtype in the neurovascular junction of the canine splenic artery.

Dissociation of potentiation of Leu31 Pro34 neuropeptide Y on adrenergic and purinergic transmission in isolated canine splenic artery.

The present study observed the effects of an activation of neuropeptide Y (NPY) Y1 receptors on adrenergic and purinergic components of double-peaked vasoconstrictor responses to periarterial nerve stimulation in the isolated, perfused canine splenic arteries. The results showed that 3-30 nM Leu31 Pro34 neuropeptide Y (LP-NPY) produced a dose-dependent potentiation of double-peaked vasoconstrictor responses to trains of 30-s pulses at 1, 4 or 10 Hz of stimulation. The potentiation of LP-NPY of the nerve-stimulated vasoconstrictions were completely inhibited by subsequent blockade of alpha1-adrenoceptors or Y1 receptors with 0.1 microM prazosin or with 1 microM BIBP 3226 ((R)-N2-(diphenylacetyl)-N-[(4-hydroxyphenyl)methyl]-argininami de), respectively. The remaining responses in the presence of LP-NPY and prazosin were abolished by P2X receptor desensitization with 1 microM alpha,beta-methylene ATP. Moreover, 30 nM LP-NPY failed to modify the vasoconstrictor responses to nerve stimulation after treatment with prazosin. A subsequent administration of alpha,beta-methylene ATP completely suppressed the remaining responses after prazosin and LP-NPY. The vasoconstrictions induced by 0.003-1 nmol noradrenaline and 0.003-1 micromol ATP were slightly, but not significantly enhanced by 30 nM LP-NPY. The observations indicated that activation of postjunctional NPY Y1 receptors may have an important role in the modulation of adrenergic rather than purinergic transmission of the sympathetic co-transmission.

Effects of a selective neuropeptide Y Y(1) receptor antagonist BIBP 3226 on double peaked vasoconstrictor responses to periarterial nerve stimulation in canine splenic arteries.

The periarterial electrical nerve stimulation (30 s trains of pulses at a frequency of 1, 4 or 10 Hz) induced a double peaked vasoconstriction consisting of an initial transient constriction (first peak) followed by a prolonged response (second peak) in the isolated, perfused canine splenic artery. At low frequencies (1 and 4 Hz), a neuropeptide Y (NPY) Y(1) receptor antagonist BIBP 3226 (0.1-1 microM) produced a dose-dependent inhibitory effect on the second peak, but did not modify the first peak. At a high frequency (10 Hz), 1 microM BIBP 3226 induced a slight, but significant inhibition on both the first and second peaked responses. At a low frequency (1 Hz), the first peak was not influenced by blockade of alpha(1)-adrenoceptors or NPY Y(1) receptors with prazosin (0.1 microM) or BIBP 3226 (1 microM), respectively, but abolished by P2X receptor desensitization with alpha,beta-methylene ATP (alphabeta-m ATP, 1 microM). At a high frequency (10 Hz), the first peak was mostly inhibited by alphabeta-m ATP and partially by prazosin and BIBP 3226. On the other hand, the second peak at a low frequency was largely decreased by BIBP 3226 and partially by prazosin and alphabeta-m ATP, whereas at a high frequency, it was largely attenuated by prazosin and partially by alphabeta-m ATP and BIBP 3226. The results suggest that at a low frequency, the firstly transient constriction of double peaked responses is mainly induced via an activation of P2X-receptors, whereas at a high frequency, it is mostly mediated by the P2X-receptors, and partially by alpha(1)-receptors and NPY Y(1)-receptors. The secondary prolonged vasoconstriction at frequencies used is predominantly mediated via both alpha(1)-receptor and NPY Y(1) receptor activations, and in part by P2X-receptors. Furthermore, an activation of NPY Y(1) receptors may play an important role in evoking the prolonged vasoconstrictor response to longer pulse trains of stimulation at a low frequency, whereas an alpha(1)-adrenoceptor activation exerts a main vasomotor effect for the prolonged response at a high frequency.

Effects of neuropeptide Y on double-peaked constrictor responses to periarterial nerve stimulation in isolated, perfused canine splenic arteries.

The periarterial electrical nerve stimulation readily induced a double-peaked vasoconstriction in the isolated, perfused canine splenic artery. P2X-Purinoceptors have previously been shown to be involved mainly in the 1st-phase response and alpha 1-adrenoceptors, mostly in the 2nd-one. The dose used of neuropeptide Y (NPY) (0.01-0.1 microM) given into the preparation caused a slight but insignificant vasoconstriction. The treatment with NPY at concentrations of 0.01-0.1 microM produced a parallel inhibition on the 1st- and 2nd-phase responses following nerve stimulation at the frequencies used (1-10 Hz) in a dose-dependent manner. The vasoconstrictor responses to administered ATP (0.01-1 mumol) or noradrenaline (0.03-3 nmol) were slightly but not significantly potentiated by 0.1 microM NPY. The results indicate that NPY predominantly exerts a prejunctionally inhibitory modulation on the purinergic and adrenergic transmission in peripheral sympathetic nerves innervating the canine splenic artery.

Perivascular purinergic nerve-induced vasoconstrictions in canine isolated splenic arteries.

We tried to induce selective perivascular purinergic nerve stimulation in isolated canine splenic arterial preparations, using the cannula insertion method. Under the conditions of periarterial electrical stimulation (ES), i.e., trains of 1, 3 and 10 pulses, 1-ms pulse duration and 10-V amplitude at 1 Hz, monophasic vasoconstriction was consistently induced. The ES-induced vasoconstriction was not influenced by prazosin in doses that completely inhibited noradrenaline-induced vasoconstrictions, but it was suppressed by alpha,beta-methylene ATP, a P2X purinoceptor desensitizer. Thus, it is indicated that a selective purinergic transmitter release is readily obtained in the isolated splenic arterial preparation.

Effects of omega-conotoxin GVIA and diltiazem on double peaked vasoconstrictor responses to periarterial electric nerve stimulation in isolated canine splenic artery.

The actions of omega-conotoxin (omega-CTX) and diltiazem on adrenergic and purinergic components of double peaked vasoconstrictor responses to periarterial nerve stimulation have been investigated in the isolated, perfused canine splenic arterial preparation. Double peaked vasoconstrictions (biphases of vasoconstrictors) were consistently observed in the conditions of 30 s trains of pulses at 1 - 10 Hz frequencies. omega-CTX (1 - 30 nM) produced similar inhibitory effects on the first phase and second phase responses in a dose-related manner. Thirty nM omega-CTX almost completely inhibited the biphasic vasoconstrictions at any used frequencies but did not affect the vasoconstrictor responses to exogenous applied ATP (0.01 - 1 micromol) and noradrenaline (0.03 - 3 nmol). Intraluminal application of a large dose of diltiazem (3 - 10 microM) also produced a dose-dependent inhibitory effect on biphasic vasoconstrictions at any used frequencies. Three microM diltiazem exerted rather a larger inhibitory effect on the second phase than the first phase response at low frequencies (1 - 3 Hz), but a similar inhibition on first and second phasic responses at high frequencies (6 - 10 Hz). An extremely high dose of diltiazem (10 microM) almost completely inhibited the biphasic vasoconstrictor responses to nerve stimulation, and slightly inhibited the contractile responses to exogenous applied ATP (0.01 - 1 micromol) and noradrenaline (0.03 - 3 nmol). The present results indicate that omega-CTX selectively acts prejunctionally to inhibit the release of transmitters from sympathetic nerve terminals, and omega-CTX-sensitive calcium channels may produce a parallel controlling of purinergic and adrenergic components of sympathetic cotransmission. A large dose of diltiazem has inhibitory effects on both prejunctional and postjunctional sympathetic co-transmission. British Journal of Pharmacology (2000) 129, 47 - 52

Differential blocking effects of tetrodotoxin on double-peaked vasoconstrictor responses to periarterial nerve stimulation in canine isolated, perfused splenic artery.

1. In the present study, we investigated the effects of progressive inhibition of neuronal sodium channels by increasing concentrations of tetrodotoxin (TTX; 1-30 nmol/L) on the double-peaked vasoconstrictor responses to electrical periarterial nerve stimulation in the canine isolated and perfused splenic artery. 2. Double-peaked vasoconstrictions (biphasic vasoconstrictor responses) were consistently observed in following electrical stimulation with 30 s trains of pulses at 1-10 Hz. At low frequencies of stimulation (1-3 Hz), a submaximal concentration of 3 nmol/L TTX had no effect on the first phase of the contractile response, but almost completely inhibited the second-phase response. At high frequencies (6-10 Hz), the two vasoconstrictor phases were almost equally inhibited by 50% by 3 nmol/L TTX. A three-fold increase in the concentration of TTX used (10 nmol/L) abolished the second-phase vasoconstriction at all stimulation frequencies tested, whereas this concentration of TTX failed to block the first-phase response. Further increasing the concentration of TTX to 30 nmol/L completely blocked the remaining first-phase response. 3. Treatment with 0.1 mumol/L prazosin did not modify the first-phase response to any of the stimulation frequencies in the presence of 3 nmol/L TTX. Moreover, 0.1 mumol/L prazosin had no affect on the second-phase response at low frequencies (1-3 Hz), while at high frequencies (6-10 Hz) it slightly, but significantly inhibited the second-phase response. The vasoconstrictor responses that persisted after 3 nmol/L TTX and 0.1 mumol/L prazosin were completely suppressed by subsequent application of 1 mumol/L alpha, beta-methylene ATP at all stimulation frequencies (1-10 Hz). 4. In conclusion, progressive inhibition of sodium channels by increasing the concentration of TTX may exert a more preferential inhibition on adrenergic rather than purinergic components, suggesting that TTX-sensitive sodium channels may have a more important role in determining the adrenergic rather than purinergic transmission of sympathetic nerves.

Dissociation of inhibitory effects of guanethidine on adrenergic and on purinergic transmission in isolated canine splenic artery.

The aim of this study was both to investigate the effects of progressive inhibition of adrenergic neurons by increasing concentrations of guanethidine (0.1-10 microM) on the double-peaked vasoconstrictor responses to electrical periarterial nerve stimulation in the isolated and perfused canine splenic artery, and to clarify whether release of noradrenaline is presynaptically separate from release of adenosine 5'-triphosphate (ATP). Double-peaked vasoconstrictions (biphases of vasoconstrictions) were consistently observed under the conditions of 30-s trains of pulses at 1-10 Hz frequencies. Guanethidine, at a lower concentration (0.1 microM) did not modify the first (1st) phase vasoconstriction at low frequencies (1-2 Hz), but markedly inhibited the second (2nd) responses. On the other hand, it slightly but significantly inhibited the double-peaked vasoconstrictor responses at high frequencies (6-10 Hz). Furthermore, a 10-fold increase of concentration of guanethidine (1 microM) almost completely inhibited the 2nd phase responses at any frequencies used but did not completely inhibit the 1st phase response. A further increased concentration of guanethidine (10 microM) failed to enhance the 1 microM guanethidine-induced inhibition. The 1 microM guanethidine-resistant 1st phase responses at any frequencies used (1-10 Hz) were sensitive to tetrodotoxin (30 nM). Treatment with 0.1 microM prazosin did not modify the 1st phase response at any frequencies used in the 1 microM guanethidine-treated preparation. The responses remaining after 1 microM guanethidine and 0.1 microM prazosin were completely suppressed by a subsequent application of 1 microM alpha,beta-methylene ATP at any frequencies used. The results indicated that guanethidine, an adrenergic neuron blocker, may exert a dominant inhibitory effect on adrenergic rather than on purinergic components of sympathetic nerve co-transmission, indicating that guanethidine-sensitive mechanisms may mainly contribute to determine noradrenaline secretion from neurosecretory vesicles rather than ATP secretion.

Effects of prolonged cold storage on double peaked vasoconstrictor responses to periarterial nerve stimulation in isolated canine splenic arteries.

1. P2X-Purinoceptors and alpha1-adrenoceptors have previously been shown to involve in the double peaked vasoconstrictor responses to periarterial electrical nerve stimulation in the isolated and perfused canine splenic artery. The present study made an attempt to investigate effects of prolonged cold storage (7 days at 4 degrees C) on vasoconstrictor responses to periarterial electrical nerve stimulation, tyramine, noradrenaline and adenosine 5'-triphosphate (ATP) in the isolated canine splenic artery. 2. The periarterial nerve stimulation (1-10 Hz) readily causes a double peaked vasoconstriction in the non-stored preparations. After cold stored for 7 days, the double peaked vasoconstriction was still recognized, although the response became significantly smaller. The first phase was decreased relatively greater than the second phase by the cold storage. 3. In the cold stored preparations, the dose-response curve for tyramine was shifted to the right in a parallel manner. Prazosin almost completely inhibited tyramine-induced vasoconstriction but alpha,beta-methylene ATP failed to influence the response to tyramine. 4. The vasoconstrictor responses to noradrenaline and ATP were not significantly modified by the prolonged cold storage. 5. From these results, it is concluded that the functions of sympathetic co-transmission of purinergic components might be influenced more than that of adrenergic components in the cold storage canine splenic artery.

Effects of imipramine, an uptake inhibitor, on double-peaked constrictor responses to periarterial nerve stimulation in isolated, perfused canine splenic arteries.

Using a cannula insertion method, periarterial nerve electrical stimulations were performed at 1 and 10 Hz in the isolated, perfused canine splenic artery. Electrical nerve stimulation readily caused double-peaked vasoconstrictions. The 1st-peak response at 1 Hz was not influenced by treatment with imipramine but the 2nd one was significantly enhanced by it. The 2nd-peak response was markedly blocked by prazosin. An additional treatment with alpha,beta-methylene ATP, a P2X-purinoceptor desensitizer, abolished electrical stimulation-induced vascular responses that remained. At 10 Hz, the responses to electrical stimulation were not significantly influenced by imipramine. On the other hand, the imipramine treatment inhibited the tyramine-induced vasoconstriction but potentiated the noradrenaline-induced one. ATP-induced responses were not modified by imipramine. From these results, it is concluded that 1) the 1st-peaked constriction is mainly due to a P2X-purinoceptor-dependent mechanism, 2) the 2nd one is mainly due to an alpha1-adrenoceptor-dependent mechanism, and 3) presynaptic uptake mechanisms may perform an important role in the regulation of vascular reactivity, especially at a low frequency.

Pharmacological analysis of vasoconstrictor responses to periarterial purinergic nerve stimulation.

1. Periarterial electrical nerve stimulation at a low frequency (1 Hz) readily induced a vasoconstrictor response of the canine splenic artery in a pulse number-related manner (1-30 pulses of trains). The vasoconstrictor response to trains of up to 10 pulses at 1 Hz of stimulation appeared to be monophasic, whereas it became clearly distinguished into two phases at a longer train of 30 pulses. 2. The monophasic vasoconstrictor responses to trains of 1, 3 or 10 pulses were not modified by an alpha1-adrenoceptor blocking agent, prazosin (0.1 microM), but were completely inhibited by the P2X receptor desensitization with alpha,beta-methylene adenosine 5'-triphosphate (alpha,beta-methylene ATP; 1 microM). The 1st phase of vasoconstriction induced by a train length of 30 pulses was not influenced by the treatment with prazosin, but was abolished by alpha,beta-methylene ATP. The 2nd phase response was markedly inhibited by prazosin, and the remaining response of this phase was blocked by alpha,beta-methylene ATP. 3. Rauwolscine (0.3 microM), an alpha2-adrenoceptor antagonist, enhanced the vasoconstrictor responses to trains of 1, 3 or 10 pulses. Particularly at 10 pulses of electrical stimulation, the vasoconstrictor responses were significantly potentiated. The blockade of neuronal uptake of noradrenaline with imipramine (1 microM) did not affect the vasoconstrictor responses to trains of 1, 3 or 10 pulses. 4. It is concluded that short pulse trains of stimulation at a low frequency may selectively activate a purinergic component of sympathetic cotransmission, and the prejunctional alpha2-adrenergic feedback mechanism may tonically participate into the modulation of ATP release. Imipramine-sensitive neuronal uptake mechanism may not play an important role in regulating vascular responses to periarterial purinergic nerve stimulation.

Effects of adrenergic and cholinergic drugs on splenic arteries and veins from hooded seals (Cystophora cristata).

Isolated ring preparations of arteries and veins from hooded seal spleens were subjected in vitro to adrenaline (A), noradrenaline (NA), isoprenaline (Iso), and acetylcholine (ACh), alone or in combination with the blockers phentolamine (Phe), propranolol (Pro), and atropine (Atr). Both arteries and veins constricted in response to A (the estimated effective dose required for half-maximal response (ED50) was 3.3 and 0.2 microM, for arteries and veins, respectively) and NA (estimated ED50 was 1.5 and 0.6 microM, for arteries and veins, respectively), but these effects were abolished when the drugs were given in combination with the alpha-adrenoceptor blocker Phe. The responses of arteries and veins to ACh and the beta-adrenoceptor agonist Iso were minor and inconsistent, and were completely abolished when combined with their respective blockers (Atr and Pro, respectively). The ED50 for both A and NA are quite high in relation to normal plasma levels of A and NA in seals. This implies that these vessels (and, hence, the supply of blood to the spleen) primarily are subjected to neurogenic, rather than humoral physiological control.