Thrombectomy with embed aspiration in acute ischaemic stroke.

BACKGROUND: In addition to stent retrievers, direct aspiration has become a reasonable thrombectomy strategy. OBJECTIVES: We carried out the thrombectomy by guiding the aspiration catheter fully over the clot and performing immediate manual aspiration; we call this procedure "embed aspiration". METHODS: In this prospective, non-randomised, single-centre study, we included all patients treated at a high volume-of-care stroke centre between 2017 and 2018 for the TRIANA (Thrombectomy in Andalusia using Aspiration) registry. Thrombectomy was carried out by embed aspiration. Patients were classified according to the success (eTICI 2b67-2c-3) or failure (eTICI 0-1-2a-2b50) of the procedure. Baseline clinical data and outcomes were compared, and multivariate analysis was performed. RESULTS: The embed aspiration technique was used in 370 patients. Treatment was successful in 90.3% of patients. Mean puncture-to-recanalisation time was 25 minutes. The overall rate of good outcomes (mRS 0-2) at 3 months was 64%. CONCLUSIONS: This study supports real-life evidence that standardised embed aspiration may be an alternative to stent retrievers for thrombectomy.

First-Pass Effect in M1-Occlusion Stroke Patients Treated with Combined Stent-Retriever/Large-Bore Distal Aspiration Catheter Thrombectomy.

INTRODUCTION: Combined stent-retriever/large-bore distal aspiration catheter (LB-DAC) thrombectomy was recently introduced to treat large-vessel occlusion; however, it is unclear whether larger inner diameters improve outcomes. We compared angiographic and clinical outcomes in patients with occlusions of the M1 segment of the middle cerebral artery treated with mechanical thrombectomy using extra-LB-DAC versus LB-DAC in combination with stent-retrievers. METHODS: We analyzed consecutive patients with M1 occlusion included in the ROSSETTI registry treated with non-balloon guide catheter combined LB-DAC/stent-retriever thrombectomy between June 2019 and April 2022. We compared demographics, baseline clinical variables, procedural variables, angiographic outcomes, and clinical outcomes [National Institute of Health Stroke Scale score at 24 h (24h-NIHSS) and modified Rankin scale score at 3 months] between patients treated with extra-LB-DAC (Sofia Plus, MIVI Q6, Catalyst7; inner diameter, 0.068″-0.070″) versus LB-DAC (Sofia 5F, MIVI Q5, Catalyst 6; inner diameter, 0.055″-0.064″). Primary outcome was the first-pass effect (FPE) rate, defined as near-complete/complete reperfusion (mTICI 2c-3) after a single pass of the device. RESULTS: We included 324 patients (extra-LB-DAC, 185, 57.1% patients). Demographics, clinical data, and clinical outcomes were similar between the two groups; however, there was a trend towards improvement in National Institute of Health Stroke Scale score at 24 h (24h-NIHSS) in the cohort treated with extra-LB-DAC 9 points (IQR 4;16 points) vs. 12 points (IQR 4;18 points, P = 0.083). Patients treated with extra-LB-DAC had higher FPE rate (47% vs. 30.9%; P = 0.003) and higher modified FPE (mTICI ≥ 2b after a single pass) rate (65.9% vs 46.8%; P = 0.001). The use of extra-LB-DAC was an independent factor in predicting FPE (odds ratio 1.982, 95% confidence interval 1.250-3.143, P = 0.004). CONCLUSION: Our results suggest that in combined LB-DAC/stent-retriever thrombectomy, a larger aspiration catheter inner diameter is associated with higher rates of FPE and mFPE.

Usefulness of CT angiography for characterizing cerebral arteriovenous malformations presenting as hemorrhage: comparison with digital subtraction angiography. / Utilidad de la angio-TC para la caracterización de malformaciones arteriovenosas cerebrales con presentación hemorrágica comparada con la angiografía por sustracción digital.

OBJECTIVE: To compare the usefulness of CT angiography against the gold standard, digital subtraction angiography (DSA), in the characterization of cerebral arteriovenous malformations (AVM) that present with bleeding. MATERIAL AND METHODS: We retrospectively analyzed patients with intracranial bleeding due to an AVM who were included in a prospective database in the period comprising January 2007 through December 2012. We reviewed radiologic variables such as the characteristics of the AVM (size, location, presence of deep venous drainage), involvement of eloquent areas, and the presence of associated aneurysms. Two neuroradiologists blinded to clinical and radiological information analyzed the CT and DSA in consensus. RESULTS: A total of 22 patients were included in the study. CT angiography correctly classified 15 of the 16 cases of AVM measuring less than 3cm (93.75% sensitivity). All cases of deep venous drainage and all those located in eloquent areas were correctly detected (100% sensitivity). The presence of any type of aneurysm related with the AVM was detected in 13 of 15 cases (86.6% sensitivity); 7 of 9 of the intranidal aneurysms were detected (77.78% sensitivity), as were 6 of the 9 flow aneurysms (66.67% sensitivity). CONCLUSION: CT angiography is highly sensitive in the characterization of cerebral AVMs measuring less than 3cm, of those located in eloquent areas, and of those with deep venous drainage; it is also highly sensitive in detecting aneurysms related with AVMs. However, CT angiography is less sensitive in detecting intranidal and flow aneurysms related with AVMs.

Value of Posterior circulation ASPECTS and Pons-Midbrain Index on non-contrast CT and CT Angiography Source Images in patients with basilar artery occlusion recanalized after mechanical thrombectomy. / Valor de la escala ASPECTS de circulación posterior y del índice puente-mesencéfalo en imágenes de TC sin contraste y angiografía por TC en pacientes con oclusiones de la arteria basilar recanalizados tras trombectomía mecánica.

PURPOSE: Endovascular treatment with mechanical thrombectomy devices demonstrated high recanalization rates but functional outcome did not correlate with high rates of recanalization obtained. Patient selection prior to the endovascular treatment is very important in the final outcome of the patient. The primary aim of our study was to evaluate the prognostic value of posterior circulation Alberta Stroke Program Early CT Score (pc-ASPECTS) and Pons-Midbrain Index (PMI) scores in patients with Basilar Artery Occlusion (BAO) treated with successful angiographic recanalization after mechanical thrombectomy. METHODS: Retrospective single-center study including 18 patients between 2008 and 2013 who had acute basilar artery occlusion managed with endovascular treatment within 24hours from symptoms onset and with successful angiographic recanalization. The patients were initially classified into two groups according to clinical outcome and mortality at 90 days. For analysis we also divided patients into groups based on pc-ASPECTS (≥8vs.<8) and PMI (≥3vs.<3) on non-contrast CT (NCCT) and CT Angiography Source Images (CTASI). Imaging data were correlated to clinical outcome and mortality rate. RESULTS: CTASI pc-ASPECTS, dichotomized at <8 versus≥8, was associated with a favorable outcome (RR: 2.6; 95% CI: 1.3-5.2) and a reduced risk of death (RR: 6.5: 95% CI: 7.8-23.3). All patients that survived and were functionally independent had pc-ASPECTS score≥8. None of the 5 patients with CTASI pc-ASPECTS score less than 8 survived. CONCLUSION: PC-ASPECTS on CTASI is helpful for predicting functional outcome after BAO recanalization with endovascular treatment. These results should be validated in a randomized controlled trial in order to decide whether or not to treat a patient with BAO.

Posttreatment Infarct Volumes when Compared with 24-Hour and 90-Day Clinical Outcomes: Insights from the REVASCAT Randomized Controlled Trial.

BACKGROUND AND PURPOSE: Endovascular therapy has become the standard of care for patients with disabling anterior circulation ischemic stroke due to proximal intracranial thrombi. Our aim was to determine whether the beneficial effect of endovascular treatment on functional outcome could be explained by a reduction in posttreatment infarct volume in the Endovascular Revascularization With Solitaire Device Versus Best Medical Therapy in Anterior Circulation Stroke Within 8 Hours (REVASCAT) trial. MATERIALS AND METHODS: The REVASCAT trial was a multicenter randomized open-label trial with blinded outcome evaluation. Among 206 enrolled subjects (endovascular treatment, n = 103; control, n = 103), posttreatment infarct volume was measured in 204 subjects. Posttreatment infarct volumes were compared with treatment assignment and recanalization status. Appropriate statistical models were used to assess the relationship among baseline clinical and imaging variables, posttreatment infarct volume, the 24-hour NIHSS score, and functional status with the 90-day modified Rankin Scale score. RESULTS: The median posttreatment infarct volume in all subjects was 23.7 mL (interquartile range = 68.9 mL) and 16.3 mL (interquartile range = 50.2 mL) in the endovascular treatment arm and 38.6 mL (interquartile range = 74.9 mL) in the control arm (P = .02 for endovascular treatment versus control subjects). Baseline NIHSS (P < .01), site of occlusion (P < .03), baseline NCCT ASPECTS (P < .01), and recanalization status (P = .02) were independently associated with posttreatment infarct volume. Baseline NIHSS (P < .01), time from symptom onset to randomization (P = .02), treatment type (P = .04), and recanalization status (P < .01) were independently associated with the 24-hour NIHSS scores. The 24-hour NIHSS score strongly mediated the relationship between treatment type and 90-day mRS (P < .01 for indirect effect when adjusted for age), while posttreatment infarct volume did not (P = .26). CONCLUSIONS: Endovascular treatment saves brain and improves 90-day clinical outcomes primarily through a beneficial effect on the 24-hour stroke severity.

Perfusion Deficits and Mismatch in Patients with Acute Lacunar Infarcts Studied with Whole-Brain CT Perfusion.

BACKGROUND AND PURPOSE: The incidence and significance of perfusion abnormalities on brain imaging in patients with lacunar infarct are controversial. We studied the diagnostic yield of CTP and the type of perfusion abnormalities in patients presenting with a lacunar syndrome and in those with MR imaging-confirmed lacunar infarcts. MATERIALS AND METHODS: A cohort of 33 patients with lacunar syndrome underwent whole-brain CTP on admission. Twenty-eight patients had an acute ischemic lesion at follow-up MR imaging; 16 were classified as lacunar infarcts. Two independent readers evaluated NCCT and CTP to compare their diagnostic yield. In patients with DWI-confirmed lacunar infarcts and visible deficits on CTP, the presence of mismatch tissue was measured by using different perfusion thresholds. RESULTS: The symptomatic acute lesion was seen on CTP in 50% of patients presenting with a lacunar syndrome compared with only 17% on NCCT, and in 62% on CTP compared with 19% on NCCT, respectively, in patients with DWI-confirmed lacunar infarcts. CTP was more sensitive in supratentorial than in infratentorial lesions. In the nonblinded analysis, a perfusion deficit was observed in 12/16 patients with DWI-confirmed lacunar infarcts. The proportion of mismatch tissue was similar in patients with lacunar infarcts or nonlacunar strokes (32% versus 36%, P = .734). CONCLUSIONS: Whole-brain CTP is superior to NCCT in identifying small ischemic lesions, including lacunar infarcts, in patients presenting with a lacunar syndrome. Perfusion deficits and mismatch are frequent in lacunar infarcts, but larger studies are warranted to elucidate the clinical significance of these CTP findings.

Accuracy and reproducibility of patient-specific hemodynamic models of stented intracranial aneurysms: report on the Virtual Intracranial Stenting Challenge 2011.

Validation studies are prerequisites for computational fluid dynamics (CFD) simulations to be accepted as part of clinical decision-making. This paper reports on the 2011 edition of the Virtual Intracranial Stenting Challenge. The challenge aimed to assess the reproducibility with which research groups can simulate the velocity field in an intracranial aneurysm, both untreated and treated with five different configurations of high-porosity stents. Particle imaging velocimetry (PIV) measurements were obtained to validate the untreated velocity field. Six participants, totaling three CFD solvers, were provided with surface meshes of the vascular geometry and the deployed stent geometries, and flow rate boundary conditions for all inlets and outlets. As output, they were invited to submit an abstract to the 8th International Interdisciplinary Cerebrovascular Symposium 2011 (ICS'11), outlining their methods and giving their interpretation of the performance of each stent configuration. After the challenge, all CFD solutions were collected and analyzed. To quantitatively analyze the data, we calculated the root-mean-square error (RMSE) over uniformly distributed nodes on a plane slicing the main flow jet along its axis and normalized it with the maximum velocity on the slice of the untreated case (NRMSE). Good agreement was found between CFD and PIV with a NRMSE of 7.28%. Excellent agreement was found between CFD solutions, both untreated and treated. The maximum difference between any two groups (along a line perpendicular to the main flow jet) was 4.0 mm/s, i.e. 4.1% of the maximum velocity of the untreated case, and the average NRMSE was 0.47% (range 0.28-1.03%). In conclusion, given geometry and flow rates, research groups can accurately simulate the velocity field inside an intracranial aneurysm-as assessed by comparison with in vitro measurements-and find excellent agreement on the hemodynamic effect of different stent configurations.

The cyclooxygenase and nitric oxide synthesis/pathways mediate the inhibitory serotonergic response to the pressor effect elicited by sympathetic stimulation in long-term diabetic pithed rats.

We investigated the mechanisms involved in the 5-hydroxytriptaminergic inhibitory action on the pressor responses elicited by sympathostimulation in long-term-diabetic pithed rats. Diabetes was induced in rats by alloxan administration. Eight weeks later, the animals were anaesthetized and pithed. The action and mechanisms of 5-HT were analysed based on the pressor responses induced by sympathostimulation. In 8-week-diabetic animals, 5-HT (20 µg/kg/min) inhibits the pressor effect of sympathostimulation which is reproduced by two selective 5-HT(1A) and 5-HT(2) receptor agonists: 8-hydroxydipropylaminotetralin hydrobromide (8-OH-DPAT, 5 µg/kg/min) and α-methyl-5-HT (5 µg/kg/min). A bolus injection of 1H-[1,2,4] oxadiazolo[4,3-a] quinoxalin-1-one (ODQ, 10 µg/kg), or L-arginine HCl, N(ω)-L-arginine methyl ester hydrochloride (L-NAME, 10 mg/kg), an inhibitor of NO production, prior to the infusion of 8-OH-DPAT (5 µg/kg/min) reversed the inhibitory effect of 8-OH-DPAT. The inhibitory effect of infusion of α-methyl 5-HT (5 µg/kg/min) was abolished in the presence of indomethacin (2 mg/kg), a non-selective cyclooxygenase (COX) inhibitor, or FR 122047 (1.5 mg/kg) or nimesulide (1.5 mg/kg), two selective COX-1 and COX-2 inhibitors, respectively, in long-term-diabetic pithed rats. Our results indicate that 5-HT inhibition of the pressor responses induced by electrical stimulation is mediated both by the NO and COX pathways in long-term-diabetic rats.

Effect of 5-hydroxytryptamine on neurogenic vasoconstriction in the isolated, autoperfused hindquarters of the rat.

1. In the present study, we analysed the effect of different doses of 5-hydroxytryptamine (5-HT; intravenous infusions of 0.001-40 microg/kg per min) in the autoperfused hindquarters of the rat subjected to electrical stimulation (frequencies of 0.5-20 Hz) of the lumbar chains, investigating the relationship between the adrenergic and serotonergic systems in this vascular bed. 2. Because we observed that 5-HT inhibited the increases in perfusion pressure induced by electrical stimulation of the lumbar chains, we used different agonists and antagonists to analyse the mechanism of action of 5-HT. 3. The effect of 5-HT was inhibited by methiothepin (a non-specific 5-HT receptor antagonist), but not by ritanserin (a selective 5-HT2 receptor antagonist). The effects of 5-HT were mimicked by 5-carboxamidotryptamine (a 5-HT1 receptor agonist) and L-694 247 (a selective 5-HT1D receptor agonist), but not by 8-hydroxy-2-dipropylaminotetralin (a 5-HT1A receptor agonist), CGS-12066B (a 5-HT1B receptor agonist), alpha-methyl-5-HT (a 5-HT2 receptor agonist), 1-(3-chlorophenyl) piperazine (a 5-HT2C receptor agonist) or 1-phenylbiguanide (a 5-HT3 receptor agonist). The selective 5-HT1D/1B receptor antagonist BRL 15572 inhibited the effect of the agonist L-694 247. 4. Our data suggest that 5-HT inhibits the increases in perfusion pressure induced by the electrical stimulation of the lumbar chains, acting on presynaptic 5-HT1D receptors and decreasing the release of noradrenaline from the sympathetic nerves in the hindquarter vascular bed of the rat.

m-CPP, a 5-HT2C receptor agonist that modifies the perfusion pressure of the hindquarter vascular bed of anesthetized rat.

In the present work we studied the actions of the intra-arterial administration of meta-chlorophenylpiperazine (m-CPP - a 5-HT(2C) receptor agonist) in the hindquarters of the anesthetized rat. The lowest doses used (0.001, 0.01, 0.1, 0.25 and 0.5 microg/kg) induced vasodilatation whereas the highest doses produced vasoconstriction (1, 6.25, 12.5 and 25 microg/kg). Both vasodilatation and vasoconstriction were inhibited by the 5-HT(1,2 )receptor antagonist methiothepin, whereas the 5-HT(2 )receptor antagonist ritanserin blocked only the vasoconstrictor responses. 1-[4-(1-Adamantanecarboxamido)butyl]-4-(2-methoxyphenyl)piperazine (a 5-HT(1A) receptor antagonist) and ICI 118,551 (a beta(2)-receptor antagonist) failed to modify the vasodilator responses of m-CPP. Both BRL 15572 (a 5-HT(1D) receptor antagonist) and GR 55562 (a 5-HT(1B) receptor antagonist) only partially inhibited this action. Our data reveal that m-CPP induces the 5-HT(1 )and/or non-specific vasodilator effect and 5-HT(2) vasoconstrictor effects in the hindquarter vascular bed of the rat.

Vasorelaxant effect of new neo-clerodane diterpenoids isolated from Croton schiedeanus.

The vasorelaxant effect of two new neo-clerodane diterpenoids, (12R)-12-hydroxycascarillone and 5beta-hydroxy-cis-dehydrocrotonin, in addition to the known cis-dehydrocrotonin and trans-dehydrocrotonin, all them previously isolated by us from Croton schiedeanus Schlecht, was studied in isolated aorta rings contracted by high K+ (80 mM) or phenylephrine (1 microM). According to their IC50 values to KCl induced contraction, the potency order was (12R)-12-hydroxycascarillone > cis-dehydrocrotonin > 5beta-hydroxy-cis-dehydrocrotonin > trans-dehydrocrotonin (0.3, 1.5, 96 and >100 mM, respectively). The possible cooperativity between diterpenoid compounds and the predominant flavonoid (ayanin) was studied. The vasorelaxant activity of cis-dehydrocrotonin and ayanin was increased when both compounds were incorporated simultaneously to the aortic rings precontracted with phenylephrine. These results suggest that Croton schiedeanus induces its effects via the synergistic actions of several vasodilator substances, among which neo-clerodane diterpenoids play an important role.

Vasoconstrictor responses to 5-hydroxytryptamine in the autoperfused hindquarters of spontaneously hypertensive rats.

In this work we studied the responses and receptors involved in the effects of intra-arterial 5-hydroxytryptamine (5-HT) in the in situ autoperfused hindquarters of spontaneously hypertensive rats (SHR). Intra-arterial administration of the highest doses (50-1,000 ng/kg) produced a vasoconstrictor effect that was inhibited by ritanserin (a selective 5-HT2 receptor antagonist), SB 206553 (a selective 5-HT(2B/2C) receptor antagonist) and spiperone (a nonspecific 5-HT(1/2A) receptor antagonist), and was mimicked by alpha-methyl-5-HT (a selective 5-HT2 receptor agonist) and m-CPP (a selective 5-HT2C receptor agonist), but not by the intra-arterial administration of BW 723C86, a selective 5HT2B receptor agonist. SB 206553 and spiperone inhibited alpha-methyl-5HT-induced vasoconstriction in the hindquarters of SHR. Our data suggest that the vasoconstrictor response induced by 5-HT in the autoperfused hindquarters of SHR is mainly mediated by the activation of 5-HT2A and 5-HT2C receptors.

5-Hydroxytryptamine-induced vasodilator responses in the hindquarters of the anaesthetized rat, involve beta2-adrenoceptors.

These studies were conducted to examine the role of the vasoactive mediators nitric oxide (NO) and adrenaline (epinephrine) in the serotonin (5-hydroxytryptamine; 5-HT)-induced vasodilator response in the hindquarter vascular bed of anaesthetized rats. Intra-arterial administration of doses of 5-HT in the range 0.12-25 ng kg(-1) produced a dose-independent vasodilator effect in the hindquarters. The selective 5-HT(1D/1B) receptor agonist, L-694,247 at intra-arterial doses of 0.0012-1000 ng kg(-1), as well as adrenaline (at doses of 0.05-50 ng kg(-1) i.a.), mimicked the dose-independent vasodilator effect induced by intra-arterial administration of 5-HT. Intravenous pre-treatment with the selective beta2-receptor antagonist ICI 118,551 (0.5 mg kg(-1)) blocked the vasodilator effect of 5-HT, adrenaline and L-694,247. Additionally, the inhibitor of NO synthase NG-nitro-L-arginine (L-NAME) (at a dose of 10 mg kg(-1) i.v.) blocked the vasodilator action of acetylcholine 300-3000 ng kg(-1)) but did not modify 5-HT-induced vasodilatation. The vasodilator effect produced by intra-arterial administration of 5-HT in the hindquarters was significantly inhibited both 30 min after denervation of the lumbar sympathetic chains and 1 h after bilateral adrenalectomy. Our data suggest that in the in-situ autoperfused hindquarters of the rat 5-HT-induced vasodilatation is mediated by a local 5-HT(1D) or 5-HT(1D/1B) activation, which in turn mediates the adrenal release of adrenaline, which then produces beta2-activation and vasodilatation.

Quercetin 3,7-dimethyl ether: a vasorelaxant flavonoid isolated from Croton schiedeanus Schlecht.

The vasorelaxant profile of quercetin 3,7-dimethyl ether, a flavonoid isolated from Croton schiedeanus Schlecht (Euphorbiaceae), was assessed in aortic rings isolated from Wistar rats. To gain insight into its structure-activity relationship, we compared this substance with quercetin 3,4',7-trimethyl ether (ayanin), another flavonoid isolated from this plant, quercetin 3,3',4',7-tetramethyl ether, a flavonoid synthesized by us, and quercetin. In addition we examined the interaction of quercetin 3,7-dimethyl ether with the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway. According to their pEC50 values (concentration producing a 50% inhibition of the maximal contractile response) to phenylephrine-induced precontraction in rat isolated aorta, the potency order was quercetin 3,7-dimethyl ether > quercetin > quercetin 3,4',7-trimethyl ether > quercetin 3,3',4',7-tetramethyl ether (4.70+/-0.18; 3.96+/-0.07; 3.64+/-0.02; 3.11+/-0.16). The relaxant effect of quercetin 3,7-dimethyl ether was significantly decreased by the removal of endothelium as well as by methylene blue, an inhibitor of guanylyl cyclase, and by N(G)-nitro-L-arginine methyl ester hydrochloride (L-NAME), an NO-synthase inhibitor. Therefore, quercetin 3,7-dimethyl ether has a NO/cGMP pathway-related profile, with increased vasorelaxant activity due to hydroxylation at positions 3 and 4 of the B ring. In addition, methylation at positions 3 and 7 with respect to quercetin of the C and A rings, respectively, seems to further enhance the vasorelaxant activity of quercetin 3,7-dimethyl ether.

Vasodilator and vasoconstrictor responses induced by 5-hydroxytryptamine in the in situ blood autoperfused hindquarters of the anaesthetized rat.

In the present study we attempted to characterise the responses and receptors involved in the effects of 5-hydroxytryptamine (5-HT, serotonin) in in situ autoperfused rat hindquarters. Intra-arterial administration of the lowest doses of 5-HT used (0.12-12.5 ng/kg) induced vasodilator responses, whereas the highest doses (25-1000 ng/kg) produced vasoconstriction. The vasodilator effect was inhibited by methiothepin (a non-specific 5-HT(1,2,5,6,7) receptor antagonist) and by a 5-HT(1D/1B) receptor antagonist, i.e., 3-[4-(4-chlorophenyl)piperazin-1-yl]-1,1-diphenyl-2-propanolol (BRL 15572), but not by ritanserin (a selective 5-HT(2) receptor antagonist), 5-methyl-1-(3-pyridylcarbamoyl)-1,2,3,5-tetrahydropyrrolo[2,3-f] indole (SB 206553, a selective 5-HT(2B/2C) receptor antagonist) or mesulergine (a non-specific serotonergic antagonist that shows affinity to the 5-HT(7) receptor). This vasodilator effect was mimicked by administration of a selective 5-HT(1) receptor agonist - 5-carboxamidotryptamine (5-CT) - and by 2-[5-[3-(4-methylsulphonylamino)benzyl-1,2,4-1 H-indol-3-yl]ethanamine (L-694,247, a selective 5-HT(1D/1B) receptor agonist). Methiothepin, but not mesulergine, inhibited 5-CT-induced vasodilatation and the selective 5-HT(1D/1B) receptor antagonist (BRL 15572) inhibited the vasodilator action induced by L-694,247. The vasoconstrictor effect of 5-HT was significantly decreased by methiothepin, ritanserin and SB 206553, and was mimicked by alpha-methyl-5-HT (a selective 5-HT(2) receptor agonist) but not by administration of BW 723C86, a selective 5HT(2B) receptor agonist. Ritanserin, SB 206553 and spiperone (a non-specific 5-HT(1/2A) receptor antagonist) inhibited the alpha-methyl-5HT-induced vasoconstriction.Our data suggest that the vasodilator response induced by 5-HT in autoperfused rat hindquarters is mainly mediated by 5-HT(1D/1B) receptors, whereas the vasoconstrictor effect is mainly due to the activation of 5-HT(2A) receptors.

Inhibitory effect of N(G)-nitro-L-arginine methyl ester on the anti-adrenergic response elicited by ayanin in the pithed rat.

In this study we evaluated the anti-adrenergic response elicited by ayanin, a flavonoid compound isolated from Croton schiedeanus Schlecht, in the pithed rat, and the inhibitory effect of NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME), and its acute toxicity profile in mice. In pithed rats ayanin (5 - 50 mg/kg i. v.) caused a dose-dependent decrease in the pressor and chronotropic responses induced by intravenous noradrenaline administration (0.25 microg/kg). This anti-adrenergic response was completely abolished by prior treatment with L-NAME (10 mg/kg i.v ) and the inhibitory effect of L-NAME was reversed after intravenous administration of L-arginine (100 mg/kg, i. v.). No lethal or major toxic effects were observed in mice receiving i. p. administration of ayanin up to a dose of 500 mg/kg. Our findings confirm that ayanin exerts protective cardiovascular effects against the increase in blood pressure and heart rate mainly through a mechanism that depends on the NO/cyclic guanosine monophosphate (cGMP) pathway without acute toxic effects. These results suggest that extracts of Croton schiedeanus, the native south American plant from which ayanin was isolated, might be beneficial in cardiovascular disease.