Monophosphoryl lipid A-induced delayed preconditioning is mediated by calcitonin gene-related peptide

The delayed preconditioning of the heart by monophosphoryl lipid A is mediated by endogenous nitric oxide (NO), and the cardioprotection afforded by nitroglycerin is related to stimulation of calcitonin gene-related peptide (CGRP) release. The objective of this study was to explore whether improvement of preservation with cardioplegia by monophosphoryl lipid A is mediated by CGRP. In addition, we examined the effect of monophosphoryl lipid A on the tumor necrosis factor-alpha (TNF-alpha) content of myocardial tissues. The isolated rat heart was perfused in the Langendorff mode. Heart rate, coronary flow, left-ventricular pressure, and its first derivatives (+/-dp/dt(max)) were recorded, and plasma levels of NO and CGRP, the release of creatine kinase in coronary effluent and the content of TNF-alpha in myocardial tissues were measured. Hypothermic ischemia for 4 h caused a decline in cardiac function, and an increase in the release of creatine kinase and in the content of TNF-alpha. Pretreatment with monophosphoryl lipid A (500 microg/kg, i.p.) for 24 h improved the recovery of cardiac function and reduced the release of creatine kinase concomitantly with a decrease in the content of cardiac TNF-alpha. Monophosphoryl lipid A markedly increased plasma concentrations of CGRP and NO. After pretreatment with L-nitroarginine methyl ester (L-NAME), the cardioprotection and the increased release of NO and CGRP induced by monophosphoryl lipid A were abolished. Capsaicin also abolished the cardioprotection and the increased release of CGRP induced by monophosphoryl lipid A, but did not affect the content of NO. The results suggest that monophosphoryl lipid A-induced preconditioning enhances preservation with cardioplegia and that the protective effects of monophosphoryl lipid A are related to stimulation of CGRP release.     

The cardioprotection of calcitonin gene-related peptide-mediated preconditioning

Preconditioning induced by brief ischemia or hyperthermia or some drugs shows two phases, early and delayed protection. The cardioprotection afforded by preconditioning is related to stimulation of endogenous mediators release. Calcitonin gene-related peptide (CGRP), a major transmitter of capsaicin-sensitive sensory nerves, has recently been shown to play an important role in mediation of the preconditioning induced by brief ischemia or hyperthermia or by some drugs, and alpha-CGRP seems to play a major role in the mediation of delayed preconditioning. It has been shown that the cardioprotection afforded by CGRP-mediated preconditioning is due to inhibition of cardiac tumor necrosis factor-alpha (TNF-alpha) production, but not to the activation of the K(ATP) channel.     

Involvement of capsaicin-sensitive sensory nerves in early and delayed cardioprotection induced by a brief ischaemia of the small intestine

Early cardioprotection can be achieved by a brief ischaemia of noncardiac tissues. Our study examined whether a brief ischaemia of the small intestine induces both early and delayed cardioprotection in the rabbit and assessed the possible mechanism involved in the activation of capsaicin-sensitive sensory nerves. The plasma concentration of creatine kinase (CK) and infarct size (necrotic zone/left ventricular zone) after 30 min coronary artery occlusion and 180 min reperfusion were determined in rabbits. Infarct size was 35.5±6.8% in the control non-preconditioned group. Preconditioning induced by a brief period of 10-min small intestine ischaemia significantly reduced infarct size (6.5±1.9%, P<0.01 vs. the control non-preconditioned group) and decreased CK release (3092±236 and 1094±117 U/l for myocardial ischaemia-reperfusion and preconditioning plus myocardial ischemia-reperfusion, respectively, P<0.01), and the protection was partly abolished by pretreatment with capsaicin (50 mg/kg, s.c.) 4 days before the experiments. A brief period of anterior mesenteric artery occlusion caused an increase in the plasma level of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI), an effect which was abolished by pretreatment with capsaicin. Similar protection was shown in the animals subjected to a brief period of anterior mesenteric artery occlusion 24 h before coronary artery occlusion, and this delayed protection was also abolished partly by pretreatment with capsaicin. Capsaicin treatment (50 mg/kg, s.c.) alone also protected the ischa-emic myocardium. The results suggest that brief ischaemia of the small intestine induces both early and delayed protection against reperfusion-induced myocardial injury, and the effects are, at least partly, related to the activation of capsaicin-sensitive sensory nerves. Received: 13 August 1998 / Accepted: 4 January 1999     

降钙素基因相关肽与高血压

感觉神经广泛分布于全身血管组织 ,通过释放多种血管活性神经肽调节心血管功能。降钙素基因相关肽是辣椒素敏感感觉神经的重要肽类递质 ,为目前已知的舒血管作用最强的物质。在高血压患者及多种实验性高血压动物中降钙素基因相关肽的合成和释放均发生改变 ,对高血压的发生、发展起着重要的作用     

Homologous desensitization of calcitonin gene-related peptide-induced relaxation in rat intramural coronary arteries

We investigated the type of desensitization of calcitonin gene-related peptide (CGRP)-induced responses in rat isolated intramural coronary arteries using isometric myograph and FURA-2 technique. In coronary arteries precontracted with 9,11-dideoxy-11alpha,9alpha-epoxymethanoprostaglandin F2alpha (U46619), development of tachyphylaxis to CGRP is characterized by significant attenuation of CGRP-induced maximal reduction in the tension and [Ca2+](i) during the second CGRP concentration-response curve; however, there was no further reduction in the CGRP-induced maximum relaxation during the third CGRP concentration-response curve. There was no sign of tachyphylaxis to CGRP when CGRP concentration-response curves were recorded in 36 mM K+-depolarized coronary arteries contrary to the results obtained in 300 nM U46619-precontracted coronary arteries. Preincubation with colchicine did not prevent the development of tachyphylaxis to CGRP in U46619-precontracted coronary arteries, indicating no role for endocytosis. Development of tachyphylaxis to CGRP was completely abolished by preincubating the coronary arteries with 1 microM RO 31-8220, indicating a role for protein kinases. Pre-exposure of the coronary arteries to isoprenaline or forskolin did not attenuate the CGRP-induced relaxation in these vessels, indicating that the cAMP-protein kinase A (PKA) pathway is not involved. Like CGRP, the coronary arteries developed tachyphylaxis toward isoprenaline during the second exposure. However, there was no sign of tachyphylaxis to either forskolin or dibutyryl cAMP (dbcAMP) during the second exposure. In conclusion, these results suggest that development of tachyphylaxis to CGRP in U46619-precontracted coronary is related to CGRP receptor-mediated activation of protein kinase.     

Role of calcitonin gene-related peptide in ischaemic preconditioning in diabetic rat hearts

1. It has been suggested that calcitonin gene-related peptide (CGRP) is involved in the protection provided by ischaemic preconditioning in rat hearts and that ischaemic preconditioning is absent in diabetic rat hearts. 2. In the present study, we tested the relationship between sensory nerve function and ischaemic preconditioning in diabetic rats. 3. In 4- and 8-week diabetic rats and age-matched non- diabetic controls, 30 min global ischaemia and 40 min reperfusion caused a significant decrease in cardiac function and a marked increase in creatine kinase (CK) release. Ischaemic preconditioning, by three cycles of 5 min ischaemia and 5 min reperfusion, improved the recovery of cardiac function and decreased CK release during reperfusion in 4-week diabetic rat hearts. However, the cardioprotection afforded by ischaemic preconditioning was lost in 8-week diabetic rat hearts. Pretreatment with CGRP for 5 min also significantly improved the recovery of cardiac function and decreased CK release in rats subjected to 4 or 8 weeks of diabetes. 4. The content of CGRP in the coronary effluent during ischaemic preconditioning was significantly increased in 4-week diabetic rat hearts (P < 0.05). However, only a slight increase in the release of CGRP was shown in 8-week diabetic rat hearts (P > 0.05). 5. In summary, the present results suggest that the protection afforded by ischaemic preconditioning is attenuated in diabetic rats and that the change may be related to the reduction in CGRP release in diabetic rat hearts.     

应激状态下大鼠颞颌关节内降钙素基因相关肽的变化

目的通过观察应激状态下髁突软骨细胞内降钙素基因相关肽(CGRP)的变化,探讨应激对颞下颌关节的可能致病机制。方法建立应激动物模型,运用RT-PCR技术检测对照组、应激组与药物对照组大鼠髁突软骨细胞CGRPmRNA表达。结果在第10天时应激组CGRPmRNA表达最高。药物对照组CGRPmRNA的表达也有升高。第20天时应激组CGRPmRNA与第10天时相比显著降低(P<0.05),但高于对照组(P<0.05)。药物对照组水平接近对照组(P>0.05)。30 d时应激组和药物对照组CGRP水平回落到对照组水平(P>0.05)。结论应激可能在TMD形成过程中起着重要作用。     

降钙素基因相关肽对大鼠小肠缺血预适应的保护作用

目的探讨降钙素基因相关肽(CGRP)在大鼠小肠缺血预适应中的作用及意义。方法①健康Wistar雄性大鼠,体质量(280±30)g,分为3组(各8只),对照组(CON):仅分离肠系膜上动脉(SMA),不夹闭,观察90 min;缺血再灌组(I/R):分离SMA,夹闭30 min,再灌注60 min,结束实验;缺血预适应组(IP):分离SMA,夹闭SMA 5 min反复3次,然后再夹闭30 min,再灌注60 min,结束实验。②利用放射免疫法测定CGRP含量,以乳酸脱氢酶(LDH)、丙二醛(MDA)含量变化和形态学变化为指标,评价缺血再灌注损伤。结果缺血预适应可明显抑制大鼠小肠缺血再灌注损伤后LDH的水平增高,降低MDA的含量(P<0.01),保护小肠黏膜不受损伤。结论CGRP为大鼠小肠缺血再灌注损伤中关键性介质之一,缺血预适应可提高大鼠小肠缺血再灌注后CGRP的水平,对抗缺血再灌注损伤。     

Comparing the role of glutathione-S-transferase and mitochondrial aldehyde dehydrogenase in nitroglycerin biotransformation and the correlation with calcitonin gene-related peptide

Both glutathione-S-transferase (GST) and mitochondrial aldehyde dehydrogenase (ALDH-2) have been reported to participate in the biotransformation of nitroglycerin. In this study, we explored which is the major player in nitroglycerin biotransformation. In vivo, rats were treated with nitroglycerin, the blood pressure and plasma calcitonin gene-related peptide (CGRP) were measured. The inhibitor of GST (ethacrynic acid) or ALDH-2 (cyanamide) was given before nitroglycerin treatment; In vitro, the isolated aorta rings were incubated with nitroglycerin to obtain the concentration–response curve. Ethacrynic acid or cyanamide was pre-incubated with the rings before nitroglycerin treatment. The release of CGRP from the aorta rings was determined. Both ethacrynic acid and cyanamide were able to reverse the depressant action of nitroglycerin while the inhibitory effect of cyanamide was more profound. However, combined administration of both inhibitors did not produce an additive effect. The change of plasma CGRP level positively correlated with the change of nitroglycerin-induced hypotensive effects. In the isolated aorta rings, vasodilator responses to nitroglycerin were reduced in the presence of ethacrynic acid or cyanamide while the inhibitory effect of cyanamide was more profound. However, combined administration of both inhibitors did not produce an additive effect. The change of CGRP release from the rings positively correlated with the nitroglycerin-induced vasodilator responses. The present results suggest that both GST and ALDH-2 are involved in nitroglycerin action while ALDH-2 plays a major role, and the change of CGRP contents closely correlates with the biotransformation of nitroglycerin.     

Involvement of calcitonin gene-related peptide in the depressor effects of losartan and perindopril in rats

Previous investigations have indicated that calcitonin gene-related peptide (CGRP) plays an important role in the regulation of cardiovascular function, and that the development of hypertension may be related to the reduction of sensory vasodilator nerve actions. In the present study, we examined the effect of perindopril, an angiotensin-converting enzyme inhibitor, and losartan, an angiotensin II receptor antagonist, on the plasma level and synthesis of CGRP in 2 kidneys, 1-clip hypertensive rats (2K1C, Goldblatt). In the hypertension group, systolic blood pressure and mean artery pressure were raised, and the level of CGRP in plasma was slightly raised compared with control groups. Chronic treatment with losartan or perindopril significantly increased the plasma concentration of CGRP and the expression of CGRP mRNA in dorsal root ganglia in the 2K1C, Goldblatt hypertensive rats. These results suggest that the 2K1C, Goldblatt hypertensive model has a compensatory increase of sensory nerve actions, and that the depressor effects of perindopril or losartan may be related to stimulation of the synthesis and release of CGRP in the 2K1C, Goldblatt hypertensive rats.     

Involvement of calcitonin gene-related peptide (CGRP) receptors in insulin-induced vasodilatation in mesenteric resistance blood vessels of rats

1. The vascular effect of insulin in the mesenteric resistance blood vessel and the role of calcitonin gene-related peptide (CGRP)-receptor in insulin-induced vascular responsiveness were investigated in rats.
2. The mesenteric vascular beds isolated from Wistar rats were perfused with Krebs solution, and perfusion pressure was measured with a pressure transducer. In preparations contracted by perfusion with Krebs solution containing methoxamine in the presence of guanethidine, the perfusion of insulin (from 0.1 to 3000 nM) caused a concentration-dependent decrease in perfusion pressure due to vasodilatation. The pD₂ value and maximum relaxation (%) were 6.94±0.22 and 43.9±5.2, respectively.
3. This vasodilator response to insulin was unaffected by 100 nM propranolol (β-adrenoceptor antagonist) plus 100 nM atropine (muscarinic cholinoceptor antagonist), 100 μM L-N^G-nitroarginine (nitric oxide synthase inhibitor), 1 μM ouabain (Na⁺-K⁺ ATPase inhibitor), or 1 μM glibenclamide (ATP sensitive K⁺-channel inhibitor).
4. In preparations without endothelium, perfusion of insulin produced a marked vasodilatation. The pD₂ value and maximum relaxation (%) were 7.62±0.21 and 81.0±4.6, respectively, significantly greater than in preparations with intact endothelium.
5. The vasodilator responses to insulin in the preparations without endothelium were significantly inhibited by CGRP[8–37], a CGRP receptor antagonist, whereas pretreatment with capsaisin, a toxin for CGRP-containing nerves, did not affect insulin-induced vasodilatation.
6. These results suggest that insulin induces non-adrenergic, non-cholinergic and endothelium-independent vasodilatation, which is partially mediated by CGRP receptors.

     

Spatial heterogeneity of the effects of calcitonin gene-related peptide (CGRP) on the microvasculature of ligaments in the rabbit knee joint

1. Experiments were performed in anaesthetized rabbits to examine the effects of calcitonin gene-related peptide (CGRP) and the CGRP antagonist CGRP_8–37 on blood flow to the medial collateral ligament of the knee joint.
2. Topical application of CGRP (10⁻¹³ to 10⁻⁹  mol) to the exposed external surface of eight knee joints resulted in dose-dependent dilatation of vessels in both the ligament and the joint capsule. The magnitude of this response varied significantly in different regions of the medial collateral ligament, with the 10⁻⁹  mol dose of CGRP giving the maximum response (101.5±25.3% increase) at the femoral insertion site of the medial collateral ligament and lowest (23.1±8.8%) at the tibial insertion site.
3. Topical application of CGRP_8–37 (0.1, 1 and 10  nmol) produced dose-dependent constriction of vessels in the ligament and the joint capsule in five knees, with a trend towards the greatest effect occurring at the femoral insertion site (45.8±8.1% reduction in blood flow). With the 10  nmol dose, the vasoconstrictor response at the femoral insertion site differed significantly (P<0.05) from the responses obtained at the tibial insertion and joint capsule sites.
4. Topical application of CGRP_8–37 (0.1, 1 and 10  nmol) to four chronically denervated knees produced substantially smaller vasoconstrictor responses at all sites. At the femoral insertion site, where 10  nmol CGRP_8–37 normally produces a 45.8±8.1% reduction in blood flow (n=8), ten days following denervation this response was reduced to 6.5±6.1%, this difference being significant (P=0.01).
5. Adrenaline was applied topically to augment blood vessel tone, in order to establish how effectively co-administration of CGRP would offset this increase in tone. Adrenaline (10⁻¹⁰  mol) produced vasoconstriction at all sites (n=6). In the capsule this vasoconstriction was virtually abolished when CGRP (10⁻⁹  mol) was co-administered with adrenaline but in the ligament vasodilatation occurred at all sites. This vasodilatation was significantly greater at the femoral insertion site compared to the tibial insertion and mid ligament sites (P<0.05 for both) and the capsule (P<0.01).
6. Topical application of substance P (10⁻¹⁰ or 10⁻⁹  mol) failed to elicit dilatation of ligament blood vessels.
7. These results suggest that endogenous CGRP may play an important role in regulating blood flow to different structures in and around the knee joint.

     

The cardioprotective effects of nitroglycerin-induced preconditioning are mediated by calcitonin gene-related peptide

Previous investigations have shown that endogenous calcitonin gene-related peptide (CGRP) may play an important role in the mediation of ischemic preconditioning and that nitroglycerin evokes the release of CGRP. In the present study, we examined whether nitroglycerin provides a preconditioning stimulus, and whether the cardioprotective effects of nitroglycerin-induced preconditioning involve endogenous CGRP. Thirty minutes of global ischemia and 30 min of reperfusion caused a significant impairment of cardiac contractile function and an increased release of creatine kinase. Pretreatment with nitroglycerin at the concentration of 3x10(-7) or 10(-6) M for 5 min produced a significant improvement of cardiac function and a decrease in the release of creatine kinase. The content of CGRP-like immunoreactivity in coronary effluent was increased during nitroglycerin perfusion. However, the cardioprotection afforded by nitroglycerin was abolished by CGRP-(8-37) (10(-7) M), a selective CGRP receptor antagonist. Pretreatment with capsaicin (50 mg/kg, s.c.), which specifically depletes the transmitter content of sensory nerves, also abolished the protective effects of nitroglycerin and markedly reduced the release of CGRP from the heart during nitroglycerin perfusion. These findings suggest that nitroglycerin-induced preconditioning is related to stimulation of CGRP release in rat hearts.     

降钙素基因相关肽在一氧化氮介导热应激诱导心肌延迟预适应中的作用

目的：研究一氧化氮－降钙素基因相关肽途径是否参与热应激诱导的心肌延迟预适应。方法：采用Langendorff装置灌注离体心脏。心脏低温（4℃）保存4h后,再灌注40min(37℃）。实验前24h大鼠进行高温处理（直肠温度42℃,15min)。记录心率,冠脉流量、左室内压以及最大变化速率,并测定血浆降钙素基因相关肽（CGRP）浓度和冠脉流出液中肌酸激酶（CK）释放量。结果：热应激能显著增强心肌停搏液的保护作用,减少CK释放量,并升高血浆CGRP浓度。这些作用能被预先给予亚硝基精氨酸甲酯及辣椒素所取消。结论：一氧化氮参与了对大鼠心脏的延迟保护,其作用是由内源性CGRP所介导。     

内毒素引起离体大鼠脊髓降钙素基因相关肽释放

本文在离体灌流大鼠脊髓片观察内毒素对感觉神经元中枢端末梢降钙素基因相关肽（ＣＧＲＰ）释放的影响．结果显示内毒素及其主要毒性成分Ａ脂均能浓度依赖性地引起ＣＧＲＰ释放，内毒素的作用可被内毒素抑制剂与钠通道阻断剂河豚毒素所阻断．采用辣椒素预温育使感觉神经末梢递质耗竭，或用辣椒素受体阻断剂ｃａｐｓａｚｅｐｉｎｅ均能显著抑制内毒素引起ＣＧＲＰ释放的作用．上述结果提示内毒素是通过其主要毒性成分＃ＦＳＡ＃ＦＫ脂，刺激辣椒素敏感的感觉神经末梢而释放ＣＧＲＰ的     

Early and delayed cardioprotection by heat stress is mediated by calcitonin gene-related peptide

Brief ischaemia or heat stress protects the myocardium against ischaemia-reperfusion injury. Heat stimulus evokes release of sensory nerve transmitters, including calcitonin gene-related peptide (CGRP). Since CGRP has been shown to play an important role in the mediation of ischaemic preconditioning, the present study examined whether early or delayed preconditioning induced by retrograde hyperthermic perfusion in vitro or by whole-body hyperthemia in vivo also involves endogenous CGRP. Isolated rat hearts were perfused in the Langendorff mode and subjected to 30 min global ischaemia and 30 min reperfusion. Heart rate, coronary flow, left ventricular pressure and its first derivatives (±dp/dt) were recorded and the CGRP-like immunoreactivity (CGRP-LI) content and the release of creatine kinase (CK) during reperfusion were measured. Retrograde hyperthermic perfusion (42 °C) for 5 min improved the recovery of cardiac function, decreased the release of CK and elevated the content of CGRP-LI in the coronary effluent. CGRP_8–37 (10^–7 mol/l), a selective CGRP receptor antagonist, abolished the cardioprotection by heat stress. Pretreatment with capsaicin (50 mg/kg s.c.), which specifically depletes sensory nerve transmitter content, abolished both the cardioprotection and the increased release of CGRP-LI. Whole-body hyperthermia (42 °C for 15 min) caused an increase in the plasma concentration of CGRP-LI. Early or delayed protection was shown in the hearts obtained from the animals subjected to whole-body hyperthermia 10 min or 48 h before the experiments. The early or delayed protection by heat stress was also abolished by pretreatment with capsaicin. The present study suggests that, in the rat, the early and delayed cardioprotection induced by heat stress involves endogenous CGRP. Received: 31 December 1998 / Accepted: 6 April 1999     

The role of activation of the sympathetic nervous system in the central pressor action of calcitonin gene-related peptide in conscious rats

The effects of intracerebroventricular (i.cv.) administration of calcitonin gene-related (CGRP) on blood pressure and heart rate (HR), and the underlying mechanisms were studied in conscious rats. CGRP (0.1–3.0 nmol i.cv.) increased mean arterial blood pressure (MABP) and HR. CGRP (3.0 nmol i.cv.) also significantly increased both plasma norepinephrine and epinephrine concentrations. Pretreatment with 16.5 nmol i.cv. CGRP(8–37), a specific CGRP receptor antagonist, significantly inhibited the i.cv. CGRP (1.0 nmol)-induced increases in MABP and HR. Phenoxybenzamine inhibited the i.c.v. CGRP-induced increase in MABP, while propranolol suppressed the tachycardiac response to i.cv. CGRP. Chemical sympathectomy by 6-hydroxydopamine inhibited the increases in MABP and HR produced by i.cv CGRP. These results suggest that the central pressor and tachycardiac effects of i.c.v. CGRP are mediated by catecholamine release due to stimulation of sympathetic nervous system activity, possibly via specific CGRP receptors in the central nervous system.This study was presented, in part, at the 14th Scientific Meeting of the International Society of Hypertension, held in Madrid, Spain in June, 1992 Correspondence to: Y. Ouchi at the above address     

Characterisation of calcitonin gene-related peptide receptors in rat atrium and vas deferens: evidence for a [Cys(Et)(2, 7)]hCGRP-preferring receptor

The present study was performed in order to characterise calcitonin gene-related peptide (CGRP) receptor subtypes in rat left atrium and vas deferens by using [R-(R*,S*)]-N-[2-[[5-amino-1-[[4-(4-pyridinyl)-1-piperazinyl]carbonyl]pentyl]amino]-1-[(3,5-dibromo-4-hydroxyphenyl)methyl]-2-oxoethyl]-4-(1,4-dihydro-2-oxo-3(2H)-quinazolinyl)-,1-Piperidinecarboxamide (BIBN4096BS), a novel CGRP receptor antagonist. When CGRP was used as an agonist, BIBN4096BS exhibited an almost 10-fold higher affinity for CGRP receptors in rat left atrium compared to those in the vas deferens, indicating that CGRP acts through different CGRP receptor subtypes in these two tissues. In addition, BIBN4096BS was almost 10-fold more potent in antagonizing [Cys(Et)^2,7]hCGRP and human adrenomedullin-induced responses than CGRP-induced responses in rat vas deferens. This might indicate receptor heterogeneity in rat vas deferens. Accordingly, the present work provides first experimental evidence that the rat vas deferens contains two CGRP-like receptor subtypes. Namely, the CGRP₂ receptor and a “novel” receptor that possesses low efficacy for CGRP and that is selectively stimulated by [Cys(Et)^2,7]hCGRP or adrenomedullin and which can be blocked with high affinity by BIBN4096BS.     

降钙素基因相关肽在前列腺素介导豚鼠心脏缺血预适应中的作用(英文)

目的:研究降钙素基因相关肽与前列腺素在豚鼠心脏缺血预适应中的相互作用。方法:采用Langen-dorff方法灌注豚鼠离体心脏。记录心率、冠脉流量、左室内压以及最大变化速率,并测定冠脉流出液中降钙素基因相关肽(CGRP)与6-酮-PGF_(1α)的释放量。结果:内皮素-1(200 pmoL)引起心功能下降,表现为冠脉流量、心率、左室内压及其最大变化速率降低。缺血预适应可明显减轻内皮素-1引起的心脏损伤,同时预适应期间CGRP与6-酮-PGF_(1α)的释放量明显增加。应用辣椒素耗竭内源性CGRP后,缺血预适应的保护作用被取消。选择性CGRP_1受体拮抗剂CGRP_(8-37)100nmol/L也能取消缺血预适应的保护作用。环氧化酶抑制剂吲哚美辛(10μmol/L)可取消缺血预适应的保护作用,同时缺血预适应促进CGRP与6-酮-PGF_(1α)释放的作用也被取消。结论:前列腺素参与了缺血预适应对豚鼠心脏的保护作用,前列腺素的作用是由CGRP所介导。     

软脉灵对动脉粥样硬化鹌鹑血浆内皮素和降钙素基因相关肽的影响

目的:观察软脉灵对动脉粥样硬化鹌鹑血浆内皮素和降钙素基因相关肽的影响。方法:雄性日本鹌鹑60只,随机均分成6组,即正常组、动脉粥样硬化模型组、软脉灵低、中、高剂量(折合成生药7.5,15和30g.kg-1)组和阳性对照普伐他汀钠8 mg.kg-1组,每组10只。除正常组外其余5组鹌鹑给予高脂饲料16周制备动脉粥样硬化模型,给药组在造模的同时,灌胃给药,qd,持续16周。16周后采血,测血浆内皮素和降钙素基因相关肽以及血清胆固醇和三酰甘油的含量;并取主动脉,观察斑块分级及主动脉内膜厚度,制作病理切片。结果:与正常对照组比较,模型组动物在喂饲高脂饲料16周后主动脉内膜厚度显著增加,动脉粥样硬化斑块形成;其血浆内皮素升高,降钙素基因相关肽降低,血清总胆固醇和三酰甘油明显升高。与模型组比较,软脉灵组剂量依赖性的减轻动脉粥样硬化斑块的形成和主动脉内膜的厚度,降低血浆内皮素及血清总胆固醇和三酰甘油,升高降钙素基因相关肽。结论:软脉灵抗动脉粥样硬化的机制可能与其降低血浆内皮素和升高降钙素基因相关肽有关。