A Reminder of Methylene Blue's Effectiveness in Treating Vasoplegic Syndrome after On-Pump Cardiac Surgery

The inflammatory response induced by cardiopulmonary bypass decreases vascular tone, which in turn can lead to vasoplegic syndrome. Indeed the hypotension consequent to on-pump cardiac surgery often necessitates vasopressor and intravenous fluid support. Methylene blue counteracts vasoplegic syndrome by inhibiting the formation of nitric oxide.We report the use of methylene blue in a 75-year-old man who developed vasoplegic syndrome after cardiac surgery. After the administration of methylene blue, his hypotension improved to the extent that he could be weaned from vasopressors. The use of methylene blue should be considered in patients who develop hypotension refractory to standard treatment after cardiac surgery.     

Dose-dependent headache response and dilatation of limb and extracranial arteries after three doses of 5-isosorbide-mononitrate

Summary The aim of the present study was to compare the ability of different doses of isosorbide-5-mononitrate (5-ISMN) to cause dilatation of medium sized and small arteries, and to examine the intensity and duration of any headache produced. Ten healthy volunteers each received 3 doses of 5-ISMN and placebo on separate days. The diameters of the radial and superficial temporal arteries were repeatedly measured with high frequency ultrasound and pain was scored using a 10 point verbal scale.A clear dose-relationship was found for plasma concentrations and headache, and for changes in the diameter of the temporal artery, but not for the radial artery.It is concluded that headache after 5-ISMN is caused by arterial dilatation or by mechanisms responsible for the arterial dilatation. Ultrasound monitoring of arterial diameters is an important and sensitive tool in the evaluation of nitrates and other vasodilators.     

左旋精氨酸与维生素B6对低密度脂蛋白抑制兔胸主动脉内皮舒张功能的影响

目的观察正常人的低密度脂蛋白(native low density lipoprotein,nLDL),人工氧化的低密度脂蛋白(oxidized lowdensity lipoprotein,ox-LDL)及非胰岛素依赖型糖尿病(Non-insulin dependent diabetes mellitus,MDDM)患者的低密度脂蛋白(diabetic low density lipoprotein,dLDL)对兔胸主动脉环内皮的损伤作用及左旋精氨酸(L-arginine,L-Arg),维生素B6(pyridoxine,VB6)的拮抗效应.方法采用离体动脉环灌流的方法,观察兔胸主动脉环对乙酰胆碱(acetycholine,Ach),钙离子载体A23187的舒张反应.结果3种LDL均抑制动脉环对Ach及A23187的舒张,损伤强度为ox-LDL＞dLDL＞nLDL,并具有浓度依赖性;L-Arg、VB6能明显拮抗LDL的抑制作用,但并不能完全逆转.以SOD作为保护药对照,250 U/ml的浓度能够显著抑制dLDL对内皮的损伤.结论3种低密度脂蛋白主要可能通过降低NO生物活性损伤内皮,L-Arg、VB6具有内皮保护作用.     

PEPTIDES AS NEUROTRANSMITTERS IN VASCULAR AUTONOMIC NEURONS

1. Neuropeptides are present in the majority of autonomic neurons projecting to blood vessels, where they are co-localized with non-peptide transmitters and sometimes with other peptides. 2. Neuropeptides are released from vasoconstrictor and vasodilator nerve terminals after high frequency stimulation (>2–5 Hz) with trains of impulses. 3. Neuropeptides can have potent post-synaptic effects on vascular tone, but often these effects are restricted to selected regions of the vasculature. 4. Post-synaptic effects of neuropeptides tend to be more slowly-developing and more long-lasting than those of non-peptide transmitters. 5. Autonomic vasoconstrictor and vasodilator responses often have multiple phases, with the faster phases being mediated by non-peptide transmitters and the slower phases mediated predominantly by one or more neuropeptides. 6. Some neuropeptides do not seem to have post-synaptic effects in a particular vascular bed, but can have presynaptic actions on neurotransmitter release. 7. Neuropeptides form an important component of the repertoire of neurotransmitters used by vascular autonomic neurons to regulate regional blood flow in response to a range of physiological stimuli.     

Relative significance of the nitric oxide (NO)/cGMP pathway and K+ channel activation in endothelium‐dependent vasodilation in the femoral artery of developing piglets

Mechanisms mediating endothelium‐dependent vasodilation were investigated in femoral artery rings from <2‐day‐old (newborn) and 2‐week‐old piglets. Based on previous results we hypothesized an age difference in the relative contribution of nitric oxide(NO)‐cyclic 3′,5′‐guanosine monophosphate (cGMP) and K⁺ channel‐activation to acetylcholine (ACh)‐induced vasodilation. Changes in vascular tone were studied in organ baths in the absence or presence of NO synthase(NOS) inhibition or K⁺ channel blockade and the intra‐arterial accumulation of cGMP in response to ACh was measured with radioimmunoassay (RIA). In control experiments, relaxant responses to ACh were equal in the two age groups. In the presence of the NOS‐inhibitors N ^G‐monomethyl‐L ‐arginine acetate (L ‐NMMA; 100 μM ) or N^G‐nitro‐L ‐arginine (L ‐NOARG; 1–100 μM ), however, relaxation was significantly more reduced in femoral artery rings from 2‐week‐old than from newborn, with lower pD₂ values in the older age group. Inhibition of large (BK_Ca) conductance calcium‐sensitive K⁺ channels with tetraethylammonium chloride (TEA; 1 mM ), gave a significant rightward shift in the concentration‐response curves to ACh which was of the same magnitude in both age groups. The ACh‐induced vasodilation was abolished in both age groups by high K⁺ (20 mM ) in combination with L ‐NOARG (100 μM ). The relative increase in cGMP levels after addition of ACh (10 nM ) was significantly larger in rings from newborn compared with 2‐week‐old piglets (12‐ vs. four‐fold). In summary, sensitivity to NOS inhibition increased with age while the effect of K⁺ channel blockade with TEA was the same in femoral artery rings from newborn to 2‐week‐old piglets. Lower sensitivity to NOS inhibition and a larger increase in cGMP in response to ACh could indicate a higher efficacy of the NO/cGMP pathway in this vessel in the newborn piglet.     

Elevation of plasma viscosity induces sustained NO-mediated dilation in the hamster cremaster microcirculation in vivo

 We studied whether a flow-independent increase of luminal wall shear stress (WSS) could dilate hamster arterioles in vivo and which endothelial mediators are potentially involved. To this end the plasma viscosity was elevated by exchanging blood for dextran-erythrocyte solution thereby augmenting WSS. Diameters of small and large arterioles as well as red blood cell velocities were measured before and after exchange of blood for solutions of identical haematocrit containing either high- (HMWD) or low-molecular weight dextran (LMWD). The potential role of endothelial autacoids was investigated by local application of the NO-synthase inhibitor N ^G-nitro-L-arginine (L-NNA), the inhibitor of cyclooxygenase, indomethacin (3 μM), or the K⁺-channel blocker, tetrabutylammonium (TBA, 0.1 mM) to assess the potential effects of EDHF. HMWD (n = 11 animals) increased plasma viscosity by 64 ± 3% and dilated arterioles of all branching orders (A1–A4) significantly [by 24 ± 3% (A1–A2) and 32 ± 3% (A3–A4)]. This dilation compensated fully for the calculated initial increase of WSS. LMWD (n = 6) did not affect plasma viscosity or arteriolar diameters. Tissue treatment with L-NNA (30–300 μM, n = 12) substantially diminished the HMWD-induced dilation in small arterioles (A3–A4; to 13 ± 3%; P<0.05) and virtually abolished it in large ones (A1–A2). Consequently, the calculated WSS increased significantly in these arterioles (by 31 ± 5%). TBA combined with L-NNA (n = 4) did not reduce further the remaining dilation. Indomethacin (n = 6) had no effect on HMWD-induced dilation. We conclude that an increase of WSS induces a mainly NO-mediated arteriolar dilation. This dilation occurs in all arteriolar branching orders and is of sufficient magnitude to compensate for the initial WSS-increase. Thus, any elevations of WSS fulfil the requirement for a signal to change diameter along the arteriolar tree in a coordinated manner. The fully compensating dilation which we observed indicates that WSS is a controlled variable. It does, however, raise questions as to its role as a continuous endothelial stimulus. Received: 2 August 1996 / Received after revision: 24 February 1997 / Accepted: 14 April 1997     

人组织激肽释放酶基因对2型糖尿病大鼠血压的影响及机制

目的：探讨人组织激肽释放酶（HK）基因对2型糖尿病大鼠血压的影响及其机制。方法:高脂高糖饮食加小剂量链脲佐菌素建立2型糖尿病动物模型。以重组腺相关病毒为载体介导HK基因（HK组）或对照基因LacZ（LacZ组）在糖尿病大鼠体内表达，观察实验动物血压变化及离体主动脉对乙酰胆碱（Ach）依赖性血管舒张反应和一氧化氮（NO）、内皮素-1（ET-1）、内皮素受体A（ETA-R）表达。 结果:(1) HK组第2周开始出现血压下降，并一直持续到实验结束（12周时），而LacZ组血压无明显下降。(2) LacZ组离体主动脉对乙酰胆碱（Ach）依赖性血管舒张反应明显低于HK组。(3) HK组大鼠主动脉NO2-/NO3-浓度明显高于LacZ组，而ET-1和ETA-R mRNA明显低于LacZ组。 结论:重组腺相关病毒介导HK基因表达明显降低2型糖尿病大鼠血压，改善内皮依赖性血管舒张功能，原因可能与增加动脉NO释放，减少ET-1和ETA-R的表达有关。     

Pinacidil,a new vasodilator,in the treatment of mild to moderate essential hypertension

Summary Twenty three patients with essential hypertension who were uncontrolled on diuretic and/or -receptor antagonist therapy were treated additionally with the vasodilator, pinacidil, in an open study. Significant reduction in mean blood pressure was achieved. Supine and erect systolic and diastolic blood pressure fell by 44/25 mmHg and 37/24 mmHg respectively over the study period of 12 weeks. Side-effects such as dizziness, headache, facial flushing and mild oedema were experienced by 10 patients during the study, all of which were mild and transient and did not require withdrawal from pinacidil therapy. Pinacidil is an effective and well tolerated agent in the treatment of essential hypertension.     

Hemodynamic differences between carvedilol and labetalol in the cutaneous circulation

The effects of labetalol and carvedilol on local cutaneous microvascular perfusion and calculated local cutaneous microvascular resistance were investigated in anesthetized rats at submaximal doses that produced equivalent reductions in blood pressure and heart rate. Labetalol decreased cutaneous perfusion (– 25% ± 3%) without significantly affecting cutaneous vascular resistance ( – 6% ± 3%). In marked contrast, carvedilol dramatically increased cutaneous perfusion ( + 64% ± 9%) and significantly reduced cutaneous vascular resistance ( – 57% ± 3%). These results suggest that carvedilol and labetalol possess differences in the mechanisms by which they produce vasodilation in vivo.     

MN9202保护血栓大鼠尾动脉血管作用

观察新二氢吡啶类钙拮抗剂２,６－二甲基－４－（３－硝基苯基）－１,４－二氢－３,５－吡啶二羧酸－３－甲酯－５－正戊酯（ＭＮ９２０２）对血栓形成大鼠尾动脉血管平滑肌及内皮功能的影响。方法大鼠脚趾ｓｃ注射角叉来胶制备血栓模型,并于注射角叉菜胶前２４ｈ,１ｈ及注射后２４ｈｉｐＭＮ９２０２１μＭＯＬ．ＫＧ＾－１,取尾动脉血栓波及不同区域的三段血管,以去甲肾上腺素（ＮＥ）,乙酰胆碱（ＡＣｈ）,亚硝酸钠（Ｎａ