利多卡因对小血管直径的影响

目的：利多卡因局部应用以解除血管痉挛。但对于其周围血管活性作用究竟是使血管扩张还是收缩，尚存在明显分歧。方法：采用展开的大白鼠睾提肌膜型，在显微镜下活体观察用肾上腺素致痉的小血管对２％、５％、１０％、２０％和２５％浓度的利多卡因局部滴注的反应，以及未致痉的小血管对２％利多卡因的反应。结果：不同浓度的利多卡因对痉挛的小动脉均有短暂的扩张作用，但１分钟后，动脉直径又开始回缩；１０分钟时，２％和５％利多卡因进一步加重了痉挛，其它浓度的利多卡因也未能解除痉挛。静脉对不同浓度的利多卡因均无明显反应。未致痉的小动脉对２％利多卡因亦呈强烈收缩反应。结论：不宜用利多卡因局部滴注以求解除血管痉挛。     

Contribution of prostaglandins in hypoxia-induced vasodilatation in isolated rabbit hearts. Relation to adenosine and KATP channels

The mechanism of hypoxia-induced coronary vasodilatation was studied in isolated, saline-perfused rabbit hearts under constant flow conditions. Reduction in the perfusion solution PO₂ (from 520±6 to 103±9 mm Hg) under control conditions halved the coronary resistance and was accompanied by a significant release of the prostaglandin (PG) 6-keto-PGF₁ (from 1.8±0.3 to a maximum of 4.4±0.9 pmol min^–1 g^–1). The cyclooxygenase inhibitor, diclofenac (1 M), blocked the release of PGI₂ and reduced hypoxia-induced vasodilatation (from 47±8% to 25±5%, P<0.05). The relative contribution of adenosine, prostaglandins, and adenosine triphosphate (ATP)-sensitive K⁺ channel (K_ATP channel) activation in hypoxia-induced vasodilatation was assessed by comparing the differential change (control response minus response after treatment) in coronary perfusion pressure (CPP) during infusion of 8-phenyltheophylline (8-PT), diclofenac, and glibenclamide, respectively. The differential change in CPP with 8-PT and diclofenac given together (–48 ±7%) was found to be equivalent to the sum of their respective effects (–24±7 and –19±4%, respectively). Glibenclamide (0.3 M) reduced significantly hypoxia-induced vasodilatation (differential change in CPP of –27±6%) as well as the dilator response to 10 M adenosine and to the stable PGI₂-analogue, iloprost. Forskolin-induced coronary vasodilatation in arrested hearts was slightly, but significantly, reduced by glibenclamide. Our results suggest that both cyclooxygenase products and adenosine, acting independently and concomitantly, contribute to the dilator response of coronary resistance vessels to hypoxia, in part through the activation of K_ATP channels. K_ATP channel activation by prostacyclin and adenosine may involve both cyclic adenosine monophosphate-dependent and independent pathways.     

Effects of exercise on vasodilatory capacity in endurance- and resistance-trained men

To determine vasodilatory responsiveness we measured forearm blood flow (FBF) following reactive hyperemia (RH), prior to and following a bout of maximal aerobic exercise in endurance- (n=14) and resistance-trained men (n=10). Both groups were similar in height, body mass, and percentage body fat. Using strain-gauge plethysmography, resting FBF was higher in the resistance-trained group [4.82 (0.84) vs 3.33 (1.17) ml min⁻¹ 100 ml⁻¹ of tissue; P<0.05]. However, the resistance-trained group had a 17%–29% lower pre-exercise FBF response to RH for the first 45 s (P<0.05). Following the maximal exercise bout there were no group differences in FBF. Post-exercise FBF was higher compared to pre-exercise values in both the endurance- (P<0.001) and resistance- (P<0.01) trained groups. Endurance-trained men appear to have a greater peak vasodilatory capacity compared to resistance-trained men, and acute maximal exercise increased the vasodilatory capacity in both groups. Acute exercise also equalized the peak vasodilatory response between the endurance- and resistance-trained groups, suggesting the potential for flow-mediated vasodilatation was similar for both groups. Electronic Publication     

Enzymic and nonenzymic release of NO accounts for the vasodilator activity of the metabolites of CAS 936, a novel long-acting sydnonimine derivative

Summary The molecular mechanism(s) underlying the vasodilator activity of CAS 936 (3-(cis-2,6-dimethylpiperidino)-N-(4-methoxybenzoyl)-sydnonimine) and its metabolites 3-(cis-2,6-dimethylpiperidino)-sydnonimine (C87 3754) and N-(cis-2,6-dimethylpiperidino)-N-nitroso-2-aminoacetonitril (C873786) was investigated. These compounds were tested for their relaxant activity in isolated rabbit arterial segments, activation of purified soluble guanylyl cyclase and release of nitric oxide (NO) in vitro and in vivo. C873754 and C873786 inhibited the noradrenalin-induced contraction and increased the cyclic GMP content of endothelium-denuded rabbit aortic and femoral segments, whereas CAS 936 was without effect. Similarly, both metabolites, but not CAS 936, activated purified soluble guanylyl cyclase (EC₅₀ about 30 M) and released NO in buffered aqueous solutions, as detected by electron spin resonance (esr) spectrometry. Both in vitro and in vivo an accumulation of NO was detected by esr spectrometry in vascular tissues exposed to the metabolites of CAS 936, whereas a significant release of NO from CAS 936 was only detected in the isolated rabbit liver, but not in vascular tissue. It is conceivable, therefore, that the metabolites of CAS 936 appearing in the systemic circulation after hepatic biotransformation induce vasodilatation by release of NO and activation of soluble guanylyl cyclase in vascular smooth muscle. Moreover, the activation of soluble guanylyl cyclase in vitro by the metabolites of CAS 936 was significantly enhanced by co-incubation with certain particulate fractions from bovine aortic endothelial and smooth muscle cells. Thus, an enzymic release of NO from these metabolites in addition to their spontaneous decomposition may play a significant role for their vasodilator activity in vivo.Correspondence to A. Mülsch at the above address     

Analysis of the potentiating action of NG-nitro-l-arginine on the contraction of the dog temporal artery elicited by transmural stimulation of noradrenergic nerves

Summary Dog temporal artery strips without endothelium responded to transmural electrical stimulation with a contraction which was potentiated by N^G-nitro-l-arginine (l-NNA). The noradrenaline-induced contraction and the release of 3H-noradrenaline were not affected. The stimulation-induced contraction was reversed to a relaxation by phentolamine. The relaxation was not influenced by timolol and atropine but inhibited by l-NNA; l-arginine abolished the inhibition. Transmural stimulation released NO_x from the arteries, the release being abolished by l-NNA. Potentiation by l-NNA of the neurally-induced contraction appears to be due to elimination of NO produced by non-adrenergic, non-cholinergic vasodilator nerve activation. Send offprint requests to N. Toda at the above address     

Loratadine augments emotional blushing

The aim of this study was to determine whether loratadine, a selective inverse agonist of peripheral histamine H₁ receptors, would reduce emotional blushing. Loratadine (10?mg) or placebo was administered orally one hour before 31 healthy participants sang a children's nursery rhyme to evoke embarrassment and blushing. Skin blood flow was monitored via a laser Doppler probe attached to the cheek. Increases in facial blood flow while participants sang were greater in the loratadine than the placebo group (mean increase?±?standard deviation 71?±?52% in the loratadine group versus 35?±?37%, p?=?.036). However, perceptions of blushing were similar in both groups. These findings suggest that loratadine augmented blushing rather than inhibiting it. Thus, histamine released during blushing may inhibit acute increases in facial blood flow by evoking H₁ receptor-mediated vasoconstriction.     

急性冠脉综合症的动脉粥样硬化程度及内皮功能改变

目的:探讨动脉粥样硬化及内皮功能与急性冠脉综合症(ACS)的关系。方法:以二维超声测定的颈动脉内中膜厚度(IMT)和硬化斑块指数(Plaque index,PI)作为衡量动脉粥样硬化程度的指标,测定肱动脉内径作为血管内皮舒张功能的指标。ACS组56例,对照组26例。结果:ACS组的IMT、动脉粥样硬化斑块检出率、PI明显大于对照组(P<0.05～<0.01)。ACS组与对照组相比,肱动脉内皮依赖性血管舒张功能明显受损(P<0.001),内皮非依赖性舒张功能则无明显变化(P>0.05)。结论:急性冠脉综合症患者存在严重颈动脉粥样硬化,其内皮依赖性血管舒张功能明显受损。     

Vascular effects of Tanacetum vulgare L. leaf extract: in vitro pharmacological study

Aim of the study

Tanacetum vulgare L. (Asteraceae/Compositae) is principally used in traditional Moroccan medicine as antihypertensive remedy. The aim of the present study was to investigate the in vitro vascular activity of the aqueous extract of Tanacetum vulgare L.

Materials and Methods

The activity of Tanacetum vulgare L. extract was tested on contractile response of Wistar rat aorta to high KCl and noradrenaline and on endothelium-dependent relaxation evoked by acetylcholine.

Results

The addition of Tanacetum extract during the plateau phase of noradrenaline-evoked contraction produced a rapid relaxation that reached a maximum of 30% of the contraction and was suppressed by the NO synthase inhibitor N^G-nitro-l-arginine. At higher extract concentrations this rapid relaxation was followed by a slowly developing, N^G-nitro-l-arginine-resistant, relaxing effect. Tanacetum extract also depressed KCl-evoked contraction by 30% at maximum. This effect was abolished in the presence of N^G-nitro-l-arginine. The endothelium-dependent relaxation induced by acetylcholine was depressed in the presence of Tanacetum extract in the bathing solution.

Conclusion

:This study indicates that the aqueous extract of Tanacetum possesses NO-mediated and NO-independent vasorelaxing properties in vitro.     

Effects of acupuncture on skin and muscle blood flow in healthy subjects

In 14 healthy female subjects, the effects of needle stimulation (acupuncture) on skin and muscle blood flow were investigated using a non-invasive custom-designed probe and photoplethysmography (PPG). In randomised order, 2–7 days apart, three modes of needle stimulation were performed on the anterior aspect of the tibia: superficial insertion (SF), insertion into the anterior tibial muscle (Mu), and insertion into the muscle including manipulation of the needle in order to elicit a distinct sensation of distension, heaviness or numbness (DeQi). Before intervention, the subjects rested for 30 min. After the intervention, the needle was left in situ for 20 min. Blood flow recordings were performed intermittently from 10 min prior to the intervention to the end of the trial. In a fourth session, serving as control, corresponding measurements were performed without any needle stimulation. Area under curve was calculated for 5-min periods prior to and after stimulation, respectively, and for the remaining 15-min period after stimulation. Compared to the control situation, muscle blood flow increased following both Mu and DeQi for 20 min, with the latter being more pronounced for the initial 5 min. Skin blood flow increased for 5 min following DeQi. However, no increase was found following SF. The DeQi stimulation was preceded by higher visual analogue scale ratings of anxiety prior to stimulation, which might have influenced skin blood flow to some extent. The results indicate that the intensity of the needling is of importance, the DeQi stimulation resulting in the most pronounced increase in both skin and muscle blood flow.