Cooling and response to hydrogen peroxide in human saphenous vein: role of the endothelium

In the present work we studied the responses of human saphenous vein to H2O2 and effects of moderate cooling on these responses with analysis of the role of endothelium. H2O2 (10(-7)-10(-2) M) induced concentration-dependent contraction in the intact human saphenous vein strips at both temperatures. At 28 degrees C, the maximal contraction induced by H2O2 was significantly lower than that at 37 degrees C. Compared with intact strips, the sensitivity and the maximal contraction to H2O2 were significantly enhanced in endothelium-denuded strips at 37 and 28 degrees C. However, pD2 values and maximal contractions were not significantly different in endothelium-denuded strips at different temperatures. Pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME) increased significantly the maximal contraction and sensitivity to H2O2 at 37 and 28 degrees C. The contractions increased by L-NAME were restored by the pre-incubation of l-arginine (10(-3) M) at every temperature studied. The contractile responses of intact human saphenous veins to H2O2 were reduced significantly by 10(-5) M indomethacin at both temperatures. Our results suggest that H2O2-induced contraction of human saphenous vein are mediated by its direct effect on the smooth muscle and by the generation of products of the cyclooxygenase pathway from the endothelium. Signalling pathways of these contractile effects are the same at 37 and 28 degrees C. Under normal temperature conditions, the contraction to H2O2 is possibly modulated by endothelial nitric oxide. Cooling reduces the contraction to H2O2 by increasing release of nitric oxide.     

Effects of cooling and warming on 5-hydroxytryptamine- and acetylcholine-induced contractions of human umbilical vessels: role of nitric oxide

The effects of cooling (to 28 degrees C) and warming (to 41 degrees C) on the vasoconstrictions induced by 5-hydroxytryptamine (5-HT) and acetylcholine (ACh) and the role of nitric oxide in these effects were analyzed in human umbilical artery and vein. 5-HT (10(-9)-10(-4) M) and ACh (10(-9)-10(-4) M) induced concentration-dependent contractions at 37, 28 and 41 degrees C. During cooling, the sensitivity, but not the maximal response, of 5-HT and ACh was significantly higher than at 37 degrees C; and during warming, again the sensitivity, but not the maximal response, of both contractile agents was significantly lower than at 37 degrees C. Neither cooling to 28 degrees C nor warming to 41 degrees C, after treatment with N(G)-nitro-L-arginine methyl esther (L-NAME, 10(-4) M), modify the effect of temperature in both vessels. These results suggest that cooling- and warming-induced responses in human umbilical artery and vein are independent of nitric oxide.     

Beta-2 adrenoceptor-mediated relaxation of the isolated human saphenous vein

On isolated strips of human saphenous vein, pretreated with 5 microM phenoxybenzamine and contracted with 10 mM KCl, the beta adrenoceptor mediating the relaxant effects of isoproterenol, procaterol and norepinephrine was characterized using the selective beta-1 adrenoceptor antagonist, bisoprolol, and the selective beta-2 adrenoceptor antagonist, ICI 118,551. All three agonists produced concentration-dependent relaxations of the isolated saphenous vein with an order of potency: procaterol (pD2 value, 7.69) greater than isoproterenol (pD2 value, 7.41) much greater than norepinephrine (pD2 value, 5.30). ICI 118,551 (3 X 10(-10) to 3 X 10(-9) M) was nearly 100 times more potent than bisoprolol (10(-7) to 10(-6) M) in antagonizing the relaxant effects of isoproterenol and procaterol. The slopes of the Schild plots for the antagonistic effects of ICI 118,551 and bisoprolol against isoproterenol- and procaterol-induced relaxations were not significantly different from unity indicating interaction with a homogeneous population of beta adrenoceptors. The pA2 value for ICI 118,551 amounted to 9.11 to 9.20 and for bisoprolol to 6.50 to 6.63. In addition, the concentration-response curve for the relaxant effect of norepinephrine was significantly shifted to the right by 10(-9) M ICI 118,551, but not affected by 10(-7) M bisoprolol. These results indicate that on the isolated strips of the human saphenous vein the beta adrenoceptor mediating relaxation is of the beta-2 subtype.     

Effect of cooling on alpha-1 and alpha-2 adrenergic responses in canine saphenous and femoral veins

Experiments were designed to determine the effects of cooling on alpha-1 and alpha-2 adrenergic responses in isolated canine veins. Rings of saphenous and femoral veins were suspended for isometric tension recording in modified Krebs-Ringer bicarbonate solution, gassed with 95% O2 and 5% CO2. Cooling (from 37-24 degrees C) augmented contractions to norepinephrine in saphenous but caused depression in femoral veins. Cooling (to 24 degrees C) had no effect on alpha-1 adrenergic responses evoked by phenylephrine in saphenous veins but caused depression in femoral veins. Alpha-2 adrenergic responses produced by UK 14,304 were augmented by cooling in the saphenous but were virtually abolished by cooling in femoral veins. Cooling decreased the dissociation constant (i.e., increased affinity) of corynanthine for alpha-1 adrenoceptors in saphenous and femoral veins (approximately 3-fold), and the dissociation constant of rauwolscine for alpha-2 adrenoceptors in saphenous veins (approximately 7.5-fold). The influence of cooling on alpha adrenoceptor responsiveness was analyzed using computer-generated receptor-models. The results suggest that the differential sensitivity of cutaneous and deep blood vessels to cooling results from differences in efficiency of alpha-1 and alpha-2 adrenoceptor response coupling. In the saphenous vein, there is a large alpha-1 adrenoceptor reserve which buffers the alpha-1 adrenergic response from the inhibitory influence of cooling. This coupled with a cooling-induced increase in alpha-2 adrenoceptor affinity ensures that cooling augments the response to norepinephrine. In the femoral vein, there is no alpha-1 adrenoceptor reserve and cooling therefore depresses alpha-1 adrenergic responses.(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of the nitric oxide on diazoxide-induced relaxation of the calf cardiac vein and coronary artery during cooling

The effects of cooling (to 28 °C) on the vasodilation induced by diazoxide (10⁻⁹–3 × 10⁻⁴  m ) on carbachol-pre-contracted calf cardiac vein and coronary artery and the role of nitric oxide in these effects were analyzed. Diazoxide produced concentration-dependent relaxation of calf cardiac vein and coronary artery rings pre-contracted with carbachol (10⁻⁶  m ). During cooling, the pIC₅₀ values, but not the maximal responses, to diazoxide were significantly lower than at 37 °C in both preparations. Cooling to 28 °C in the presence of N^G-nitro-L-arginine methyl ester (10⁻⁴  m ) did not modify the effect of temperature both in cardiac vein and coronary artery. These results suggest that cooling-induced changes of diazoxide in calf cardiac vein and coronary artery are independent of nitric oxide.     

颅内手术中异丙酚联合不同阿片类药物持续静脉输注的疗效比较

目的观察异丙酚联合芬太尼、舒芬太尼、瑞芬太尼持续静脉输注在颅内手术中的应用，比较其优劣。方法颅内手术患者75例，年龄20-60岁，性别不限，ASAⅡ～Ⅲ级；随机分成芬太尼组、舒芬太尼组、瑞芬太尼组。监测术中血流动力学变化，观察患者苏醒和并发症情况，进行术后VAS疼痛及OAAS意识评分。结果芬太尼在开颅、关颅、拔管时平均动脉压（MAP）、心率（HR）均明显高于基础值（P〈0．05），舒芬太尼、瑞芬太尼在开颅、颅内手术期、关颅均低于基础值（P〈0．05）；颅内手术各期芬太尼的MAP、HR值均高于舒芬太尼、瑞芬太尼组（P〈0．05），而在开颅、颅内手术期瑞芬太尼要明显低于舒芬太尼组（P〈0．05）；三组患者针刺疼痛时间舒芬太尼最长11．7±1．6（P〈0、05），瑞芬太尼最短6．0±1．2（P〈0．05）；在拔管5minOAAS评分芬太尼组最低，为2．0±0．3（P〈0．05），而舒芬太尼、瑞芬太尼组间差异无统计学意义（P〉0．05）；但术后1h、2h、4h舒芬太尼组VAS疼痛评分明显低于芬太尼、瑞芬太尼组（P〈0．05），12h达到高峰，8h后差异无统计学意义（P〉0．05）；术后恶心呕吐（PONV）发生率芬太尼组明显高于舒芬太尼、瑞芬太尼组（P〈0．05）。结论瑞芬太尼联合异丙酚持续静脉输注用于颅内手术优于芬太尼或舒芬太尼，而舒芬太尼优于芬太尼。     

Calcitonin gene-related peptide is released from capsaicin-sensitive nerve fibres and induces vasodilatation of human cerebral arteries concomitant with activation of adenylyl cyclase

The vasomotor effects of calcilonin gene-related peptide (CGRP) analogues have been studied in circular segments of fresh human cereoral arteries obtained at neurosurgical operations using a sensitive in vitro system. Human a-CGRP, human b-CGRP, rat a-CGRP and rat b-CGRP induced strong and potent relaxation of precontracted circular vessel segments. The I_max (maximum relaxant effect) to human calcitonin was low and the pD₂ (concentration for half maximum effect) 7.7 was much lower than that of CGRP. The CGRP-1, antagonist human a-CGRP_8–37 blocked the response to human a-CGRP but not to human b-CGRP, while the putative antagonist [Tyr]CGRP_28–37 did not. Capsaicin (10⁻¹⁵ - 10⁻⁸ M) caused relaxation of the cerebral arteries by 22% of precontract on. Pre-treatment with 10⁻⁶ M human a-CGRP_8–37 inhibited this relaxation. Human a-CGRP increased the cyclic AMP content of human cerebral arteries in a concentration-dependent manner. This increase in adenylyl cyclase activity was blocked by human a-CGRP_8–37. The results suggest that CGRP-1 receptors coupled to adenylyl cyclase are present in human cerebral arteries.     

Relaxant effect of N-formyl-methionyl-leucyl-phenylalanine on rabbit vascular strips

Some types of rabbit isolated blood vessels precontracted with phenylephrine relaxed when exposed to the chemotactic peptide N-formyl-Met-Leu-Phe (FMLP). The thoracic aorta was unresponsive whereas the portal vein and pulmonary artery exhibited concentration-dependent relaxing responses to FMLP (1-100 nM). FMLP-induced relaxations developed over several minutes and occurred after a latency of 30 to 40 sec. An inconsistent, brief and small contractile phase preceded the relaxations in some tissues. Stable responses to FMLP could be obtained repeatedly at 1.5-hr intervals. On both the portal vein and the pulmonary artery, the structure-activity relationship of peptides related to FMLP was similar to the one reported for activating phagocytic leukocytes. The peptide Boc-Phe-D-Leu-Phe-D-Leu-Phe behaved as a competitive antagonist of FMLP-induced relaxations with a calculated pA2 of 7.5 on both types of responsive vessels. Indomethacin inhibited the relaxations completely on the pulmonary artery and partially on the portal vein. FMLP-induced vasorelaxations were unaffected by a platelet-activating factor antagonist, BN 52021, or a 5-lipoxygenase inhibitor, L-651,392. Removal of the endothelium did not prevent the relaxant response to FMLP. The release of 6-keto-prostaglandin F1 alpha in the bathing fluid of portal vein and pulmonary artery exposed to FMLP was demonstrated using a radioimmunoassay. FMLP relaxed rabbit vascular strips in a blood-free environment by releasing secondary mediators tentatively identified as prostaglandins; however, a component of the relaxation in the portal vein was not mediated by cyclooxygenase products.     

Arachidonic acid metabolites and airway epithelium-dependent relaxant factor

Exogenous arachidonic acid (10(-8) to 10(-4) M) contracted epithelium-free guinea pig tracheal strips. Intact tracheal strips were contracted slightly by low concentrations of arachidonic acid (10(-8) to 10(-5) M), but higher concentrations relaxed them. In contrast, when tracheal strips were precontracted with histamine or carbachol, exogenous arachidonic acid had no effect on epithelium-free preparations but induced concentration-dependent (10(-8) to 10(-4) M) relaxation of intact tracheal strips. The effects of arachidonic acid both in epithelium-free and epithelium-containing trachea were blocked by either indomethacin (10(-6) M) or aspirin (10(-4) M). Studies on the effects of exogenous arachidonic acid, performed with a "sandwich protocol," demonstrated that the postulated airway epithelium-dependent relaxant factor released by an intact tracheal strip relaxes an adjacent epithelium-free strip in the same organ bath. This relaxation is antagonized by indomethacin suggesting the involvement of a cyclooxygenase product in this phenomenon. Comparison of concentration-response curves for contractile agonists in epithelium-free preparations and in one containing epithelium suggests the mobilization of airway epithelium-dependent relaxant factor by histamine but not by carbachol. The effects of cyclooxygenase and lipoxygenase inhibitors indicated that both relaxant and contractile arachidonic acid metabolites are generated by epithelial and nonepithelial cells alike in response to contractile agonists.     

Temperature-dependent basal tone in isolated human saphenous veins: implication of TP-receptors

Abstract— Cutaneous blood vessels are very sensitive to changes in environmental temperature. The influence of variations in local temperature on the mechanisms involved in the basal tone, present in isolated human saphenous veins has not yet been studied. In the present study, segments with and without endothelium of human saphenous veins obtained from coronary bypass surgery patients were mounted for isometric tension recording in oxygenated physiological salt solution (PSS). After stabilisation of the basal tone, the local temperature was rapidly either decreased from 37 °C to 24 °C (cooling) or increased from 37 °C to 42°C (warming). When antagonists or inhibitors were used the preparations were incubated for 30 min with the drugs. During basal conditions, cooling caused relaxations of the saphenous vein segments with endothelium and warming caused contractions; the absence of the endothelium did not modify these responses. In veins without endothelium, the warming‐induced contractions were significantly inhibited by verapamil (10 μM) and by the antagonist of TP‐receptors (receptors for thromboxane A₂) Bay u 3405 (1 μM). The warming induced contractions were not affected by cyclooxygenase or lipoxygenase inhibition. At 37°C, the isoprostanes (8‐iso‐PGE₂ and 8‐iso‐PGF_2α) induced potent contractions that were significantly inhibited by Bay u 3405 (1 μM). The data show that a basal tone is present in isolated resting human saphenous vein segments at 37°C. This basal tone is decreased by local cooling and enhanced by local wanning and is not dependent on the presence of the endothelium. The warming‐induced contraction of the veins is mediated by a non‐cyclooxygenase, non‐lipoxygenase metabolite (iso‐prostanc?) that interacts with TP‐receptors and via an extracellular calcium‐dependent pathway.     

Role of endothelium in magnesium-induced relaxation of rat aorta

The role of endothelium in the relaxation of rat aortic smooth muscle to raised extracellular magnesium concentration (Mg2+)o has been examined. Following contractile responses to norepinephrine (NE) or high-K+ in Mg2+-free media, cumulative increases in (Mg2+)o caused concentration-dependent relaxations in intact (+E) as well as endothelium-denuded (-E) strips. In NE-stimulated strips, Mg2+-induced relaxation was significantly greater in +E strips, whereas the reverse was the case in K+-stimulated strips. Bay K8644, a Ca2+ channel agonist, did not modify Mg2+-induced relaxation in NE-stimulated strips, but significantly attenuated the relaxation in K+-stimulated strips in the order: -E greater than +E. The results suggest that Mg2+-induced relaxation of rat aorta is associated, at least in part, with the release of an endothelium-derived relaxant factor in receptor-mediated, but not in depolarisation-dependent contractions.     

Involvement of endothelial cells in relaxation and contraction responses of the aorta to isoproterenol in naive and streptozotocin-induced diabetic rats

Experiments were designed to investigate the importance of the endothelium in the relaxation of isolated rat aorta caused by a beta adrenoceptor agonist. Mechanical removal of the endothelium attenuated the relaxation induced by isoproterenol (ISO) and did not affect the relaxation produced by forskolin and by sodium nitroprusside. High concentrations of ISO produced an increase in the resting tension of aortic strips with and without endothelium in a concentration-dependent manner. Mechanical removal of the endothelium or treatment with methylene blue enhanced the maximal contraction induced by ISO. Phentolamine antagonized the contractile responses induced by ISO. In the case of streptozotocin-induced diabetic rats, both aortic strips with and without endothelium generated concentration-response curves for ISO-induced relaxation that were shifted to the right. The relaxant responses to forskolin and sodium nitroprusside were not significantly different between vessels from diabetic and age-matched control rats. In both aortic strips with and without endothelium, the maximal contraction in response to high concentrations of ISO was significantly enhanced in strips from diabetic rats. These results suggest that ISO-induced relaxation of aortic strips with endothelium is mediated by beta adrenoceptors on both the endothelium and the smooth muscle, and high concentrations of ISO produce an increase in the resting tension through alpha adrenoceptors. It is further suggested that the decreased relaxant response of the aorta to ISO in diabetes may be due to decreased density or affinity of beta adrenoceptors on the smooth muscle.     

Effect of equivalent doses of fentanyl, sufentanil, and remifentanil on the incidence and severity of cough in patients undergoing abdominal surgery: A prospective, randomized, double-blind study

Background: Fentanyl congeners have been found to induce cough during induction of general anesthesia. Studies of fentanyl and sufentanil have found incidence rates of 28% to 65% and 15%, respectively. However, no study has assessed the occurrence of cough induced by remifentanil.Objective: The aim of this study was to assess the effect of equivalent doses of fentanyl, sufentanil, and remifentanil on cough.Methods: Patients rated American Society of Anesthesiologists class I or II of either sex, aged 18 to 60 years, who were scheduled for elective abdominal surgery with general anesthesia were randomly and equally assigned to 3 groups using a computer-generated table of random numbers. The patients received equivalent doses of fentanyl 2 μg/kg, sufentanil 0.2 μg/kg, or remifentanil 2 μg/kg via IV push. Vital signs (systolic blood pressure [SBP], heart rate [HR], and oxygen saturation via pulse oximetry [SpO₂]) and the occurrence and severity of cough were recorded for 2 minutes after drug administration by an anesthesiologist who was blinded to the drug treatment. The severity of cough was graded as none (0), mild (1–2), moderate (3–5), or severe (>5).Results: A total of 315 Chinese patients (197 women, 118 men; mean [SD] age, 37.9 [10.4] years) were approached for enrollment and assigned to 3 groups of 105 patients each; all patients completed the study protocol. The 3 treatment groups were similar in terms of demographic characteristics and type of abdominal surgery. The incidence of cough was significantly greater in the remifentanil group (57 [54.3%] patients) than in the fentanyl group (35 [33.3%]; P < 0.01) or the sufentanil group (32 [30.5%]; P < 0.01). The severity of cough was significantly greater in the remifentanil group (severe, moderate, mild, none: 24, 7, 26, 48) than in the fentanyl (7, 9, 19, 70; P < 0.01) or sufentanil group (4, 2, 26, 73; P < 0.01). In all 3 groups, when the patients coughed, significant increases were observed in their SBP (128 [12]–139 [16] mm Hg; P < 0.01) and HR (74 [10]–87 [16] beats/min; P < 0.01). Within 2 minutes after drug administration, 62 patients (59%) in the remifentanil group experienced hypoxemia (SpO₂ <90%) necessitating manually assisted mask ventilation, while no patients experienced hypoxemia in the fentanyl or sufentanil group. Three patients (2.9%) in the remifentanil group experienced muscle rigidity and deterioration of SBP, HR, and SpO₂. No other adverse events were recorded.Cunclusion: Remifentanil was associated with a significantly greater incidence and severity of cough than equivalent doses of fentanyl or sufentanil. Fentanyl and sufentanil appeared comparable in these Chinese patients undergoing abdominal surgery.     

Interaction between alpha adrenergic and serotonergic activation of canine saphenous veins.

Serotonin and norepinephrine produced concentration-dependent contractions of helical strips of canine saphenous veins. The contractile responses to both agonists were inhibited by the alpha adrenergic receptor blocking agent phentolamine. Tolazoline inhibited the contractile responses of canine saphenous veins to norepinephrine but augmented those to serotonin. Blockade of adrenergic neuronal reuptake with cocaine enhanced the sensitivity of the canine saphenous vein to serotonin, but did not suppress the inhibition by phentolamine of the contractile responses to this indolealkylamine. Serotonin-mediated venoconstriction was not secondary to release of norepinephrine since it was not accompanied by an increased release of [7-3H]-norepinephrine. These findings suggest that serotonin does not contract canine saphenous veins by stimulation of typical serotonergic receptors. The binding sites for serotonin and norepinephrine in cutaneous venous smooth muscle may share part of a common receptor complex, which triggers the contractile process. Alternatively, serotonin and norepinephrine may act at two different receptors to elicit contraction of canine saphenous veins.     

Serotonin-induced relaxation in canine coronary artery smooth muscle.

Serotonin (5-HT) is a potent contractile agonist in canine coronary artery devoid of endothelium; however, in higher concentrations 5-HT produces concentration-dependent relaxation by activating an as yet uncharacterized receptor. This study explored the possibility that 5-HT-induced relaxation was mediated by interaction with a member of the 5-HT1, 5-HT2, 5-HT3, or 5-HT4 receptor family. 5-HT, 5-carboxamidotryptamine and 5-methoxytryptamine produced concentration-dependent relaxation in vitro in tissues precontracted with prostaglandin F2 alpha (10 microM). The agonist rank order potency for relaxation was 5-carboxamidotryptamine > 5-HT > 5-MeOT. 8-hydroxydipropylaminotetralin (8-OH-DPAT), dipropyl-5-CT, 5-methyltryptamine, sumatriptan, alpha-methyl-5-HT and 2-methyl-5-HT did not produce significant relaxation. The 5-HT1/beta adrenergic receptor antagonist propranolol (1 microM) did not antagonize 5-HT-induced relaxation. 5-HT-induced relaxation was not blocked by tetrodotoxin (0.3 microM), suggesting that neuronal depolarization to release mediators from nerves was not responsible for the relaxation. Neither ketanserin (1 microM) nor ritanserin (1 microM) antagonized 5-HT-induced relaxation, suggesting that 5-HT2 and 5-HT1C receptors do not mediate relaxation. ICS 205-930 (10 microM), a 5-HT3/5-HT4 receptor antagonist, shifted the 5-HT concentration-response curve modestly to the right (pKB = 5.1 +/- 0.1). Cisapride, a 5-HT4 receptor agonist, was not effective either as an agonist (up to 10 microM), or as an antagonist (1 microM) of 5-HT-induced relaxation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Characterization of histamine receptors in isolated rabbit veins

Veins were isolated from 16 sites of the rabbit venous tree and responses to histamine and histamine receptor agonists were studied to characterize the histamine receptors. Isometric contraction and relaxation of ring segment preparations were recorded. Histamine produced concentration-dependent contractions in all veins in the resting state. Both the maximum response and pD2 value varied remarkably from vein to vein and regional differences in sensitivities to histamine varied considerably from previous findings in dog veins. Also in the precontracted state with a vasoconstricting agent, histamine predominantly contracted the veins. The contractile responses to histamine, in both resting and precontracted states, were antagonized competitively by the histamine H1-receptor antagonist, mepyramine. On the other hand, histamine relaxed the precontracted veins, in the presence of mepyramine. Selective H2-receptor agonists, dimaprit and impromidine, relaxed the precontracted veins even in the absence of mepyramine. These responses to histamine were antagonized competitively by the H2-receptor antagonist, cimetidine or ranitidine. The present study provides quantitative and systematic data regarding histamine receptors in rabbit veins. We propose that: 1) there are both vasoconstrictor H1-receptors and vasodilator H2-receptors, 2) histamine generally contracts rabbit veins through predominant H1-receptors and that 3) the H2-receptor-mediated relaxation does not depend on the presence of the endothelium.     

Sympathetic purinergic vasoconstriction and thermosensitivity in a canine cutaneous vein

In canine cutaneous veins, cooling augments the contractile responses evoked by sympathetic nerve stimulation despite a cooling-induced reduction in the release of norepinephrine. With exogenous norepinephrine, the increased responsiveness observed during cooling results from enhanced sensitivity of the postjunctional alpha-2 adrenoceptors. The present experiments were performed to analyze the mechanism of the increased neurogenic response during cooling. Rings of canine saphenous vein were suspended for isometric tension recording in organ chambers filled with modified Krebs-Ringer bicarbonate solution, gassed with 95% O2-5% CO2. Cooling (from 37-24 degrees C) increased the contractile response evoked by nerve stimulation under control conditions, after alpha-1 adrenergic blockade with prazosin, alpha-2 adrenergic blockade with rauwolscine or the combination of both antagonists. The influence of cooling to enhance the neurogenic response was inhibited only by combined alpha adrenergic and purinergic-receptor blockade (alpha,beta-methylene ATP). Electrical stimulation failed to evoke a contractile response (either at 37 or 24 degrees C) in the presence of tetrodotoxin or after acute sympathetic denervation with 6-hydroxydopamine. alpha,beta-Methylene ATP abolished the contractile response evoked by ATP but did not affect the concentration-effect curves to alpha-1 (phenylephrine) or alpha-2 (UK 14,304) adrenergic stimulation. Cooling augmented the contractile responses evoked by ATP. The results suggest that ATP released from sympathetic neurons in the vessel wall contributes to the cooling-induced augmentation of contractile responses to sympathetic nerve stimulation in canine cutaneous veins. This may explain the increased prominence of purinergic mechanisms in cutaneous blood vessels.     

Direct comparison of relaxation and cGMP production in human coronary by-pass grafts in response to stimulation with natriuretic peptides and a nitric oxide donor

In the present study, we investigated the vasodilator properties of A-type, B-type and C-type natriuretic peptides (ANP, BNP and CNP respectively) and the NO (nitric oxide) donor sin-1 (3-morpholino-sydnonimine) in human by-pass grafts. In contrast with previous studies, the same vessel was used to demonstrate a direct link between cGMP production and functional relaxation. Remnants of the IMA (internal mammary artery) and SV (saphenous vein) were obtained from 82 patients undergoing coronary artery by-pass grafting. The responses to cumulative concentrations of ANP, BNP, CNP and sin-1 in vessel rings pre-contracted with a thromboxane A2 agonist (U46619) were measured in an organ bath. Additionally, intracellular cGMP production after single submaximal dose application of these drugs to vessel rings was determined by a RIA. ANP (P=0.001) and sin-1 (P<0.001) caused significant concentration-dependent relaxation of the IMA. In the SV, only sin-1 (P<0.001) induced marked concentration-dependent relaxation. At a single submaximal concentration, significant relaxation as well as intracellular cGMP production were found in response to ANP, BNP and sin-1 in the IMA. In contrast, in the SV, only sin-1 significantly induced cGMP production and relaxation. There was a moderate, but significant, correlation between intracellular cGMP net production and net relaxation in the IMA. In conclusion, ANP, as the most powerful relaxant of all the natriuretic peptides tested on the IMA, may be a possible alternative vasorelaxant to overcome peri-operative vasospasm in this artery. In contrast with sin-1, ANP and BNP were not effective vasorelaxants of the SV. Net relaxation in response to natriuretic peptides correlated with cGMP net concentrations in the IMA.     

Warming and response to contractile agents in calf cardiac vein: role of the nitric oxide

The effects of warming on the response to various contractile agents of calf cardiac vein were studied using 2.5-mm long cylindrical segments. Concentration-response curves for carbachol (10(-9)-3 x 10(-4) m), 5-hydroxytryptamine (5-HT; 10(-8)-3 x 10(-3)), potassium chloride (KCl; 10(-4)-5 x 10(-2) m) and calcium chloride (CaCl2; 10(-4)-10(-2)) were isometrically recorded at 37 and 41 degrees C (warming). During warming the sensitivity, but not the maximal response, of carbachol 5-HT, KCl, and CaCl2 was significantly higher than at 37 degrees C. Warming to 41 degrees C after treatment with NG-nitro-L arginine methyl esther (10(-5) m) did not modify the effect of warming. These results suggest that nitric oxide seems to have no role in the warming-induced responses in calf cardiac vein.     

Cooling and alpha adrenergic responses in the saphenous vein of the rabbit

Experiments were designed to determine the effects of cooling on alpha-1 and alpha-2 adrenergic responses in a cutaneous vein of the rabbit. Rings of saphenous vein were suspended in physiological salt solution for the recording of isometric force. Cooling (from 37-24 degrees C) caused no significant increase in force in quiescent rings. Similarly, the same degree of cooling had no significant effect on the response to exogenous norepinephrine (10(-9)-10(-5) M), whether under control conditions or in the presence of either the alpha-1 adrenergic antagonist prazosin (3 X 10(-7) M) or the alpha-2 adrenergic antagonist rauwolscine (10(-7) M). Contractions evoked by the alpha-1 adrenergic agonist phenylephrine were reduced, but those induced by the alpha-2 adrenergic agonist UK 14,304 (10(-9)-10(-5) M) were unaffected by the same degree of cooling. Cooling augmented the response elicited by electrical field stimulation of the sympathetic nerves, although only under conditions of alpha-1 or combined alpha-1 and alpha-2 adrenergic blockade. Data obtained with the sympathomimetic tyramine suggest that both alpha-1 and alpha-2 adrenoceptors are innervated in this blood vessel. Together, the present data suggest that the effects of acute cooling on the saphenous vein of the rabbit, unlike that of the dog, are not mediated by changes in the affinity of postjunctional alpha-2 adrenoceptors.