Vasodilating properties of extracts from the leaves of Musanga cecropioides (R. Brown)

The mechanisms of action involved in the hypotensive properties of the aqueous extract of the leaves of Musanga cecropioides were investigated. The effect of the aqueous leaf extract of M. cecropioides, found to contain mostly saponins, flavonoids and procyanidins, was investigated on vascular smooth muscle and also in an in vivo direct invasive blood pressure study in both normotensive and hypertensive rats. The hypotensive or antihypertensive properties of the extracts appear to be due partly to a direct or indirect vasodilator effect and also to some alpha(1)- and beta(2)-adrenergic blocking effects. The extract also exhibited significant endothelium-dependent vascular smooth muscle relaxation, accounted for by the release of nitric oxide (NO), and induced significant angiotensin converting enzyme (ACE) inhibitory effects thereby supporting its vasodilator mechanism of action.     

Inhibition of platelet P2Y12 and alpha2A receptor signaling by cGMP-dependent protein kinase

The important role of cGMP and cGMP-dependent protein kinase (cGPK) for the inhibition of platelet activation and aggregation is well established and due to the inhibition of fundamental platelet responses such as agonist-stimulated calcium increase, exposure of adhesion receptors and actin polymerization. The diversity of cGMP binding proteins and their synergistic interaction with cAMP signaling in inhibiting platelets indicates that a variety of cGMP targets contribute to its antiplatelet action. Since stimulation of G(i)-proteins was recently shown to be essential for complete platelet activation/aggregation, the possibility that G(i)-signaling events are cGMP/cGPK targets was investigated. Thus, the effect of elevated cGMP levels and selective cGPK activation on purinergic and adrenergic receptor-evoked decrease of platelet cAMP content was closely examined. Experiments with a selective activator of cGPK demonstrate for the first time a cGMP-caused G(i)-protein inhibition and our data suggest that this effect is mediated by cGPK. Considering the essential role of G(i)-signaling for platelet activation, we propose that inhibition of G(i)-mediated signaling by cGMP/cGPK is an important mechanism of action underlying the platelet inhibition by cGMP-elevating endothelium derived factors and drugs.     

丁咯地尔治疗脑梗死的临床及血流动力学研究

目的　研究丁咯地尔治疗脑梗死的临床疗效并观察其对血流动力学的影响。方法　 10 0例脑梗死病人 ,随机分为治疗组和对照组 ,治疗组采用丁咯地尔注射液 2 5 0ml (含丁咯地尔 10 0mg) ,静脉滴注 ,一日一次 ,14天为一个疗程 ;对照组采用丹参注射液 2 5 0ml,静滴 ,一日一次 ,14天为一个疗程 ,观察临床疗效及血流动力学改变。结果　治疗组总有效率 92 % ,显效率 62 %。对照组总有效率 64% ,显效率 30 % (P <0 .0 5 )。丁咯地尔对脑循环动力学有显著改善 (P <0 .0 1) ,且不良反应较少。结论　丁咯地尔治疗脑梗死的疗效优于丹参注射液并可改善血流动力学     

Responses to propofol in the pulmonary vascular bed of the rat

BACKGROUND: Although a great deal is known about responses to propofol, controversy remains about its mechanism of action. The present study was undertaken to investigate the direct effects of 2,6-diisopropyl phenol, disodium edetate, and its intralipid emulsion in the rat pulmonary vascular bed and to better understand the mechanisms involved in propofol-mediated responses. METHODS: The effects of N omega-l-nitro-l-arginine benzyl ester (L-NABE), an inhibitor of nitric oxide synthase, of the cyclooxygenase blocker, meclofenamate, and the K + ATP channel antagonist, U-37883A, an ATP-sensitive potassium channel antagonist, on responses to propofol, acetylcholine, nitroglycerin, and isoproterenol were investigated in the isolated blood-perfused rat lung under low tone and high steady-state tone. RESULTS: Propofol produced a dose-dependent decrease in pulmonary arterial perfusion pressure. L-NABE significantly reduced vasodilator responses to acetylcholine, whereas the nitric oxide synthase inhibitor had no significant effect on responses to propofol. Meclofenamate significantly reduced vasodilator responses to arachidonic acid without effecting responses to propofol. Responses to propofol were not significantly changed in the presence of U-37883A, whereas U-37883A reduced vasodilator responses to levcromakalim. Additionally, 2,6-diisopropylphenol in a pure preparation as well as an intralipid preparation similar to propofol emulsion had no significant effect while disodium edetate had a dose-dependent depressor effect under high steady-state tone. CONCLUSION: Propofol has significant vasodilator activity in the pulmonary vascular bed of the rat but responses to propofol are not mediated or modulated by the release of nitric oxide, opening of K + ATP channels, or the release of vasodilator cyclooxygenase products.     

Transformed migraine is a cause of chronic daily headaches

Chronic daily headaches (CDH) consist of episodes of head pain occurring daily; more than 15 days each month; often associated with a history of migraine, with or without aura; or with a history of tension-type headaches occurring alone or both occurring together. Chronic daily headaches are frequently associated with rebound headaches after ergotamine, barbiturate, caffeine, and analgesic abuse. We previously reported that migraineurs with typical intermittent headaches exhibited excessive cerebral cortical vasodilation after oral acetazolamide which usually precipitated and reproduced their typical headaches. In the present study, cerebral vasodilator responses were tested by measuring changes in local cerebral blood flow (ΔLCBF) utilizing xenon-contrasted CT scanning, before and after oral administration of 14.3 mg/kg of acetazolamide, in 11 patients with CDH. The results were compared with 12 age-matched typical migraineurs, with and without aura, who had a history of migraine attacks occurring at intervals of 1 month or longer. Global and subcortical gray and white matter ΔLCBFs were quantitated and compared between both groups. After acetazolamide, ΔLCBF increased in cortical gray matter by 11.8% among patients with CDH and by 16.7% among migraineurs, with no significant differences between groups. Typical migraine attacks were provoked by acetazolamide in 9 patients (82%) with CDH and in 11 (92%) migraineurs with intermittent headaches. These observations are taken as evidence that at least 82% of patients with CDH have transformed migraine as judged by the provocation by acetazolamide of typical migraine attacks associated with excessive ΔLCBF increases. Serotonin agonists should be considered in the treatment of CDH to avoid ergotamine, caffeine, barbiturate, and analgesic abuse.     

Evaluation of a spasmolytic cocktail to prevent radial artery spasm during coronary procedures.

Radial artery spasm is a frequent complication of the transradial approach for coronary angiography and angioplasty. Recently, we have been able to quantify spasm using the automatic pullback device. The objective of this study was to assess the efficacy of an intra-arterial vasodilating cocktail in reducing the incidence and severity of radial artery spasm. A hundred patients undergoing coronary procedures via the radial artery were divided into two groups of 50 each. Patients in group A received intra-arterial cocktail (5 mg of verapamil plus 200 micro g nitroglycerine in 10 ml of normal saline), while patients in group B did not receive any vasodilating drug. The pullback device was used for sheath removal at the end of the procedure. Seven (14%) patients in group A experienced pain (i.e., pain score of III-V) during automatic sheath removal, as compared to 17 (34%) in group B (P = 0.019). The mean pain score was significantly lower in group A than in group B (1.7 +/- 0.94 vs. 2.08 +/- 1.07; P = 0.03). The maximal pullback force (MPF) was also significantly lower for group A (0.53 +/- 0.52 kg; range, 0.10-3.03 kg) as compared to group B (0.76 +/- 0.45 kg; range, 0.24-1.99 kg; P = 0.013). Only 4 (8%) patients in group A had an MPF value greater than 1.0 kg, suggesting the presence of significant radial artery spasm, as opposed to 11 (22%) in group B (P = 0.029). Administration of an intra-arterial vasodilating cocktail prior to sheath insertion reduces the occurrence and severity of radial artery spasm.     

静脉滴注丁咯地尔出现尿频、尿急、排尿困难2例

丁咯地尔(buflomedil)化学名为：4-(1-吡咯烷基)-1-(2，4，6-三甲氧基苯基)-1-丁酮盐酸盐。用于治疗外周血管疾病，如间歇性跛行、雷诺综合征、Burger综合征，血管性痉挛和慢性脑血管供血不足引起的眩晕、耳鸣、智力减退、记忆力或注意力消退、定向障碍等症状，是种新型的血管扩张剂。临床不良反应的报道尚不多见，到目前作者未见有丁咯地     

Design,synthesis, and biological evaluation of novel NO-releasing 4-chromanone derivatives as potential vasodilator agents

The nitric oxide/cyclic guanosine monophosphate (NO/cGMP) signaling pathway is an effective mechanism involved in the treatment of hypertension. In our search for potential antihypertensive agents, a series of novel NO-donor derivatives of the 4-chromanone skeleton were designed and synthesized by coupling furoxans or nitrooxy NO-donor moieties. All derivatives showed enhanced nitric oxide releasing capacity and vasodilator activity with EC₅₀ values ranging from 0.0215 μM to 1.46 μM, obviously superior to those of precursor 3 . These biological evaluations indicated that all compounds displayed an important vasorelaxant effect, and several compounds (9c, 14b, 14c, 14d) presented good vasodilator activity, with 14c being the best. Furthermore, molecular modeling studies revealed that compound 14c occupied the pocket well with the phosphodiesterase 5 domain in a favorable conformation. In conclusion, we observed that these novel compounds can act as structural templates for the design and subsequent development of new vasodilators and antihypertensive drugs.