Contribution of Splenic Resistance Arteries to Splanchnic Blood Overflow in Cirrhosis.

BACKGROUND: In liver cirrhosis, a marked splanchnic vasodilation causes an increase in portal blood flow, contributing to the development of portal hypertension. AIM: To evaluate if, in experimental cirrhosis, a different vascular reactivity exists between splenic and mesenteric components of the splanchnic circulation. METHODS: Liver cirrhosis was induced in Sprague Dawley rats by common bile duct ligation. In sections of splenic and superior mesenteric arteries, cumulative dose-response curves were obtained. mRNA expression of endothelial nitric oxide synthase (eNOS), inducible NOS (iNOS), and prostaglandin I2 synthase (PTGIS) was evaluated. RESULTS: In cirrhotic rats, mesenteric but not splenic arteries showed a significant increase in endothelium-dependent relaxation to acetylcholine. In control and cirrhotic rats, COX inhibition alone did not significantly change the response of mesenteric arteries to acetylcholine; after inhibiting also NOS, the relaxation was completely abolished in control but only partially decreased in cirrhotic rats. After the inhibition of COX and NOS, the relaxation to acetylcholine was similarly decreased in splenic arteries from control and cirrhotic animals. The contraction induced by phenylephrine of both mesenteric and splenic arteries was decreased in cirrhotic rats. PTGIS mRNA expression did not differ in splenic and mesenteric arteries from control and cirrhotic rats; in cirrhotic rats, eNOS and iNOS mRNA expression was increased in mesenteric but not in splenic vascular bed. CONCLUSION: In cirrhotic rats, a decreased splenic arterial response to vasoconstrictors, rather than an increased response to vasodilators, contributes to splanchnic vasodilation, while in mesenteric arteries also an increased response to vasodilators secondary to, but not only, eNOS and iNOS overexpression, plays a role.

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.

[Application of perfusion of low molecular dextran via splenic artery in portal azygous devascularization for portal hypertension].

OBJECTIVE: To evaluate the effects of the perfusion of low molecular dextran via the splenic artery in portal azygous devascularization for portal hypertension in the prevention from portal vein thrombosis. METHODS: A total of 92 patients with portal hypertension were randomly divided into a control group (46 cases) that received the extensive devascularization around the cardia, and a trial group (46 cases) that received the above-mentioned operation and the perfusion of low molecular dextran via the splenic artery. The incidence of portal vein thrombus after the operation and the preoperative and postoperative blood transfusion were observed and the results were analyzed and compared between the two groups. RESULTS: The incidence of thrombosis and blood transfusion were 26.1% (12/46) and CRBC 4~6 U respectively in the control group, while those were 4.3% (2/46) and CRBC 2~3 U respectively in the trial group. The differences were statistically significant (P < 0.05). CONCLUSION: The perfusion of low molecular dextran via the splenic artery in portal azygous devascularization for portal hypertension is effective and safe in the prevention from portal vein thrombosis.

Distinct mechanisms of relaxation to bioactive components from chamomile species in porcine isolated blood vessels.

German chamomile (Matricaria recutita L.), a widely-used herbal medicine, has been reported to have a wide range of biological effects, including smooth muscle relaxation. The aim of this study was to compare the effects of representative compounds from chamomile (apigenin, luteolin, (-)-α-bisabolol, farnesene, umbelliferone; 3-30 µM) on vascular tone using porcine coronary and splenic arteries mounted for isometric tension recording in isolated tissue baths and precontracted with the thromboxane-mimetic U46619. Apigenin, luteolin, and (-)-α-bisabolol produced slow, concentration-dependent relaxations in both the coronary and splenic arteries that were not blocked by inhibition of nitric oxide synthase or potassium channels. Removal of extracellular calcium inhibited the relaxations to all three compounds, and these compounds also inhibited calcium re-addition-evoked contractions, indicating that the relaxation response may be mediated through inhibition of calcium influx. Apigenin and luteolin, but not (-)-α-bisabolol, enhanced the relaxation to the nitric oxide donor sodium nitroprusside, indicating that apigenin and luteolin may act to regulate cyclic GMP levels. Umbelliferone produced a rapid, transient relaxation in the splenic artery, but not the coronary artery, that was inhibited by L-NAME and removal of the endothelium, suggesting an influence on nitric oxide production. Farnesene, at concentrations up to 30 µM, was without effect in either blood vessel. In conclusion, hydroxylated compounds (apigenin, luteolin and (-)-α-bisabolol) found in chamomile all caused a slow relaxation of isolated blood vessels through an effect on calcium influx. Umbelliferone, on the other hand, produced a rapid, transient relaxation dependent upon release of nitric oxide from the endothelium.

Disruption of splenic circulation using microbubble-enhanced ultrasound and prothrombin: a preliminary study.

The spleen is a solid organ in which splenomegaly frequently develops and to which abdominal blunt trauma occurs. In this study, we demonstrated the potential therapeutic effect of microbubble-enhanced ultrasound (MEUS) combined with prothrombin to disrupt splenic circulation. A high-pressure-amplitude therapeutic ultrasound (TUS) device was used to treat 36 surgically exposed spleens in healthy New Zealand rabbits. Eighteen spleens were treated with either MEUS (n = 9) or MEUS combined with prothrombin (n = 9). The other 18 spleens were treated with TUS only or sham ultrasound exposure and served as the controls. The TUS was operated at a frequency of 831 kHz and a peak negative pressure of 4.8 MPa. Prothrombin was administered intravenously at 20 IU/kg. Contrast-enhanced ultrasound (CEUS) and acoustic quantification were performed to assess splenic blood perfusion. We found significant blood perfusion slowdown and drop-off in the MEUS-treated spleens. The peak intensity dropped from 20.2 ± 2.70 dB to 11.6 ± 4.58 dB immediately after treatment. The spleens treated with the combination of MEUS and prothrombin showed consistently poor perfusion within 1 h. In histologic examination of the MEUS-treated spleens, we found significant dilatation of splenic sinuses, hemorrhage, interstitial edema and thrombosis. This study demonstrated that the vascular effects induced by microbubble-enhanced, high-pressure ultrasound can slow down or block blood perfusion in the rabbit spleen. Prothrombin helps to enhance and extend the effects for up to 1 h.

Pre-contraction with the thromboxane-mimetic U46619 enhances P2X receptor-mediated contractions in isolated porcine splenic artery.

We have previously demonstrated that the thromboxane-mimetic U46619 enhances α(2)-adrenoceptor-mediated contractions through increased activation of extracellular signal-regulated kinase (ERK). In this study, we determined whether U46619 also enhances P2X-mediated contractions through the same pathway. Segments of porcine splenic artery were mounted in isolated tissue baths. Tissues were pre-contracted with U46619 to 10-20% of the response to 60 mM KCl prior to addition of α,ß-methylene ATP (P2X receptor agonist). The effect of inhibition of ERK activation with the mitogen-activated protein (MAP)/ERK kinase inhibitor PD98059 (50 µM), Rho kinase inhibition with Y27632 (10 µM), p38 MAP kinase with SB203580 (10 µM) or L-type calcium channels with nifedipine (1 µM) on both the direct and enhanced contractions was then determined. U46619 enhanced the contractions to α,ß-methylene ATP. Although PD98059 inhibited the direct contractions to α,ß-methylene ATP, it had no effect on the U46619-enhanced contractions. Similarly, Y27632 and SB203580 inhibited the direct contractions to α,ß-methylene ATP, but had no effect on the enhanced contractions. Nifedipine inhibited the responses to α,ß-methylene ATP in the absence and presence of U46619. This study demonstrates that pre-contraction with U46619 enhances P2X-mediated contractions in the porcine splenic artery through a mechanism independent of ERK, Rho kinase and p38 MAP kinase. Further studies are required to determine the exact mechanism involved.

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.

Prostacyclin causes splenic dilation and haematological change in dogs.

1. The effect of vasodilators on spleen volume and the blood storage function is not yet well elucidated. To this end, in the present study the effects of prostacyclin, a potent vasodilator, on splenic diameter and blood cell concentrations in arterial and splenic venous blood were evaluated in anaesthetized dogs. 2. The main splenic artery and vein were dissected for measurement of splenic arterial blood flow and intra-arterial administration and for sampling of splenic venous blood, respectively. The diameter of the spleen was measured continuously by sonomicrometry. Counts of white blood cells (WBC), red blood cells (RBC) and platelets in blood sampling from the aorta and splenic vein were estimated by an automatic blood cell counter. 3. Bolus injections of prostacyclin (1-100 ng/kg) into the splenic artery produced dose-dependent increases in splenic arterial blood flow and splenic diameter associated with significant decreases in splenic venous concentrations of WBC, RBC and platelets. When splenic blood flow was kept constant, similar changes in splenic diameter and blood cell counts were observed with prostacyclin injection. 4. Splenic dilation and haematological changes induced by prostacyclin were relatively more potent than those induced by prostaglandin E(2), acetylcholine, nitroglycerin or isoproterenol when doses producing a comparable increase in splenic blood flow were compared. 5. Infusion of prostacyclin (100 ng/kg per min) into the splenic artery caused a marked increase in splenic diameter, with immediate reductions in splenic venous concentrations of WBC, RBC and platelets, followed by significant reductions in these cell counts in the general circulation. 6. These results indicate that prostacyclin produces potent and flow-independent splenic dilation that may contribute to a decrease in circulating blood cell concentrations.

Differences in alpha 1-adrenoceptor subtype-mediated vasoconstriction by tyramine and nerve stimulation in canine splenic artery.

This study was designed to clarify the alpha(1)-adrenoceptor subtypes mediating the vasoconstrictor response to tyramine in isolated and perfused canine splenic artery. It was shown that tyramine potentiated the nerve stimulation-induced second peaked vasoconstriction that was readily suppressed by prazosin treatment. A bolus injection of tyramine (0.01-0.3 micromol) caused a vasoconstriction in a dose-related manner. The tyramine-induced vasoconstriction was inhibited by WB 4101 (10 and 100 nM), an alpha(1A)-and alpha(1D)-adrenoceptor antagonist, in a concentration-related manner. Neither BMY 7378 (100 nM), a selective alpha(1D)-adrenoceptor antagonist, nor chloroethylclonidine (60 microM), an alpha(1B)- and alpha(1D)-adrenoceptor antagonist, affected the tyramine-induced response. The results indicate that the noradrenaline released by tyramine may diffuse to the extrajunctional cleft, and thus it activates the extrajunctional alpha(1A)-adrenoceptors, because nerve stimulation-evoked second peaked vasoconstrictions were markedly inhibited by chloroethylclonidine but not by WB 4101.

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.

The preferential inhibitory effect of olmesartan, a new angiotensin II type 1 antagonist, on sympathetic nerve terminals in isolated canine splenic artery.

Effects of olmesartan (RNH-6270: (5-methyl-2-oxo-1,3-dioxolen-4-yl)methoxy-4-(1-hydroxy-1-methylethyl)-2-propyl[4-[2-(tetrazol-5-yl)-phenyl]phenyl]methylimidazol-5-carboxylase, an active form of olmesartan medoxomil (CS-866)) was investigated in isolated, perfused canine splenic arterial preparations. Neither exogenous noradrenaline- nor ATP-induced vasoconstrictor responses were modified by treatment with the used concentrations of olmesartan (1-100 nM). A high concentration of 10 nM angiotensin II caused a potentiation of either noradrenaline- and ATP-induced constrictions, although 1 nM angiotensin II did not induce any potentiating effects for these responses. These potentiations were inhibited by olmesartan in a concentration-related manner. Periarterial nerve electrical stimulation (PNS) readily induced a biphasic constriction consisting of an initial P2X purinoceptor-mediated vasoconstriction followed by a prolonged mainly alpha(1)-adrenoceptor-mediated response. PNS-induced 1st and 2nd peaked responses were significantly inhibited by olmesartan in a concentration-related manner. With a low concentration of 1 nM angiotensin II, which did not induce any vascular effects by itself, PNS-induced responses were markedly enhanced. The enhanced responses were inhibited by olmesartan. It is concluded that endogenous angiotensin II exerts its stimulating action on the releases of ATP and noradrenaline from the periarterial sympathetic nerve terminal, and olmesartan has an inhibitory property on angiotensin II-induced potentiation of endogenous ATP- and noradrenaline-induced responses.

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.

Effects of reserpine on nerve stimulation-induced constrictions in canine isolated splenic artery.

1. Our previous studies have demonstrated that peri-arterial electrical nerve stimulation (PNS) of the canine splenic artery induces a double-peaked vasoconstriction consisting of an initial transient, dominantly P2X purinoceptor-mediated constriction, followed by a prolonged, mainly alpha1-adrenoceptor-induced response. In the present study, we examined the effects of reserpine on PNS-induced double-peaked responses. 2. The vasoconstrictor response to tyramine was abolished after reserpine treatment, but the responses to noradrenaline (NA) and ATP were not significantly modified. 3. The PNS-induced second peak vasoconstrictor responses were markedly reduced in reserpinized vessels, whereas the first peak vasoconstrictor responses were not so strongly influenced (i.e. they were not significantly affected at 1 Hz, but were significantly affected at 4 and 10 Hz). 4. All reserpine-resistant responses were unaffected by treatment with prazosin, but were abolished by subsequent application of alpha,beta-methylene ATP. The exposure of reserpine-treated tissues to NA almost completely restored tyramine-induced vasoconstriction and the second neurogenic peak vasoconstrictor response, but failed to affect the first neurogenic response. 5. The present results indicate that ATP and NA are cotransmitters responsible for the double-peaked vasoconstrictor responses of canine splenic artery. In addition, it is suggested that PNS causes NA release not only from intragranular NA storage sites, but also from tyramine-sensitive cytoplasmic sites.

Effect of Levovist on splanchnic hemodynamics in cirrhotic patients.

This study was aimed to assess the effect of Levovist on Doppler parameters of splanchnic hemodynamics. A total of 12 patients with cirrhosis and 12 healthy subjects underwent Doppler ultrasound (US) examination of the portal vein and of the hepatic, splenic and superior mesenteric arteries before, 5 to 8 and 12 to 15 min after the start of an 8-min long IV infusion of 2.5 g of Levovist. Mean velocity and mean diameter were calculated for the portal vein. Resistance index was determined for the arteries. A significant increase of resistance index was observed in the hepatic (0.80 +/- 0.07 vs. 0.71 +/- 0.06; p < 0.01) and splenic arteries (0.72 +/- 0.06 vs. 0.64 +/- 0.06; p < 0.01) 5 to 8 min after contrast agent injection in patients with cirrhosis, but not in controls. Neither portal vein diameter nor portal flow mean velocity changed during the test in both controls and cirrhotic patients. This effect might be related to a selective trapping of microbubbles in the altered hepatic and splenic microvasculature in patients with cirrhosis rather than being artefactual. It might have implications on harmonic imaging US protocols designed to image the cirrhotic liver in the early arterial phase.

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.

Interaction between neuropeptide Y Y1 receptors and alpha1B-adrenoceptors in the neurovascular junction of canine splenic arteries.

Previous study has demonstrated that periarterial electrical nerve stimulation (30-s trains of pulses at a frequency of 1 or 4 Hz) induces a double-peaked vasoconstriction consisting of an initial transient, predominantly P2X-receptor-mediated constriction followed by a prolonged, mainly alpha(1)-adrenoceptor-mediated response in the isolated canine splenic artery. Treatment with 8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione (BMY 7378, 0.1 micromol/l), a selective alpha(1D)-adrenoceptor antagonist, produced a slight but significant inhibition of the second peaked responses. A marked inhibition of second peaked responses was obtained by exposure of the tissues to chloroethylclonidine (60 micromol/l), an alpha(1B)- and alpha(1D)-adrenoeptor antagonist. Neither BMY 7378 nor chloroethylclonidine affected the first peaked vasoconstrictor responses. [Leu(31),Pro(34)]Neuropeptide Y (10-30 nmol/l), a selective neuropeptide Y Y(1) receptor agonist, enhanced the second peaked responses in the presence of BMY 7378 but failed to enhance the responses in the presence of chloroethylclonidine. The results indicate that the postjunctional alpha(1B)-adrenoceptor subtype is likely coupled to neuropeptide Y Y(1) receptors responsible for the cooperation of the sympathetic adrenergic and neuropeptide Yergic transmission in the canine splenic artery.

Guanylyl cyclase mediates ANP-induced vasoconstriction of murine splenic vessels.

We have previously shown that ANP causes differential constriction of the splenic vasculature of the rat (veins greater than arteries), which may be inhibited by blocking the production of cGMP with A7195. In this paper, we report experiments done on vessels derived from guanylyl cyclase (GC)-A knockout mice. Small splenic arteries ( approximately 150-microm diameter) and veins ( approximately 250-microm diameter) were dissected from male GC-A-deficient 129sv mice or age-matched wild-type controls and mounted in a wire myograph. In the wild-type mice, ANP exhibited higher potency in the veins than in the arteries (EC(50) values wild-type mice: artery, 8 +/- 3 x 10(-9) M, n = 5 vs. vein, 6 +/- 4 x 10(-10) M, n = 5; P < 0.05). The concentration-response curve for ANP-induced vasoconstriction was also shifted leftward in denuded compared with intact arteries (EC(50) values: denuded artery: 5 +/- 3 x 10(-10) M, n = 5 vs. intact artery, 8 +/- 3 x 10(-9) M, n = 5; P < 0.05), i.e., the denuded vessels were more reactive. By contrast, ANP caused no significant change in tension from baseline in intact splenic arteries, intact splenic veins, or denuded splenic arteries derived from the GC-A-deficient mice, although these vessels did show normal concentration-dependent increases in tension to phenylephrine. We conclude that ANP causes vasoconstriction in the splenic vasculature by an endothelium-independent mechanism, mediated via guanylyl cyclase.

Effects of L-765,314, a selective and potent alpha 1B-adrenoceptor antagonist, on periarterial nerve electrical stimulation-induced double-peaked constrictor responses in isolated dog splenic arteries.

The periarterial nerve electrical stimulation (PNS) at a frequency of 1 or 4 Hz (30-s trains of pulses) readily caused a double peaked vasoconstriction in the canine splenic artery. The treatment with 1 microM L-765,314, a selective and potent alpha1B-adrenoceptor antagonist, markedly inhibited the second peaked constriction, whereas it did not modify the vasoconstrictor responses to exogenous noradrenaline (0.03-1 nmol) and A61603 (1-30 pmol), a selective alpha1A-agonist. A large dose of 10 microM L-765,314 significantly blocked exogenous noradrenaline- and A61603-induced responses. It is concluded that PNS-induced responses are mediated via the postjunctional alpha1B-adrenoceptor subtype.