Effect of cooling on the responses of human saphenous vein to fentanyl, remifentanil and sufentanil

We studied the vasodilatory effects of fentanyl, remifentanil and sufentanil on the human saphenous vein strips at 37, 32 and 28 degrees C. Fentanyl produced concentration-dependent relaxation of human saphenous vein strips precontracted with 5-hydroxytryptamine (5-HT) at every temperature studied. Compared with vein strips at 37 degrees C, relaxant responses to each one concentration of fentanyl were significantly reduced at 32 and 28 degrees C. Remifentanil relaxed vein strips in a concentration-dependent way and the relaxation for all concentrations were significantly greater at 32 and 28 degrees C compared with 37 degrees C. Sufentanil produced concentration-dependent relaxation in saphenous vein strips precontracted with 5-HT. These relaxant responses were similar at 32 degrees C compared with 37 degrees C. When bath temperature was lowered from 37 to 28 degrees C, the relaxant responses to sufentanil were significantly reduced. In summary, the present study suggests that cooling reduces the relaxation caused by fentanyl and sufentanil on human saphenous veins but augments the relaxation with remifentanil. The augmented vasodilatory effect of remifentanil with cooling may be useful on systemic vascular resistance and organ preservation under hypothermic conditions like cardiopulmonary bypass surgery.     

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.     

5-Hydroxytryptamine1B receptor-mediated contraction of rabbit saphenous vein and basilar artery: role of vascular endothelium

This study characterizes the sumatriptan-sensitive [5-hydroxytryptamine (5-HT)(1B/1D)] receptor in rabbit saphenous vein and basilar artery. (S)-(-)-1-[2-[4-(4-Methoxy-phenyl)-piperazin-1-yl]-ethyl]isochroman-6-carboxylic acid methylamide (PNU-109291), a 5-HT(1D) subtype-selective agonist (human K(i) = 2.5 +/- 0.07 nM), did not contract either tissue, whereas o-methoxyphenylpiperazide derivative 4F (MPPA-4F), a 5-HT(1B) subtype-selective antagonist (human K(i) = 4.6 +/- 0.6 nM) potently inhibited sumatriptan-induced contraction in the saphenous vein and basilar artery. These results suggested that sumatriptan-induced contraction was mediated via the 5-HT(1B) receptor in these blood vessels. 5-HT(1B) receptor-mediated contraction was then compared in endothelium-intact and denuded vessels to evaluate the role of the endothelium in regulating sumatriptan-induced contractility in these tissues. The presence of an intact endothelium inhibited 5-HT(1B)-induced contraction in both tissues. Endothelial denudation or nitric-oxide synthase inhibition with N(omega) nitro-L-arginine methyl ester (L-NAME) (100 microM) increased the efficacy and potency of sumatriptan in the saphenous vein and basilar artery. Surprisingly, in endothelial-denuded vascular tissues, L-NAME (100 microM) also significantly increased the maximal 5-HT(1B) receptor-induced contraction in both tissues, with no effect on potency of sumatriptan. The effect of L-NAME after endothelial denudation may reflect the presence of a low density of residual endothelial cells as estimated by CD31 antibody staining combined with the modulating effect of nitric oxide released from nonendothelial cells in vascular tissue. Endothelial modulation was specific to 5-HT(1B) receptors because removal of the endothelium did not significantly alter contraction to norepinephrine, histamine, prostaglandin, or potassium chloride in the saphenous vein or basilar artery.     

Role of the endothelium on the response to adrenoceptor agonists of rabbit aorta during cooling

The role of the endothelium in the effects of cooling on the response to alpha1- and alpha2-adrenoceptor agonists of rabbit aorta was studied. The contractions induced by clonidine (10(-9)-3 x 10(-4) M) and xylazine (10(-7)-10(-3) M) but not phenylephrine (10(-9)-3 x 10(-4) M) and methoxamine (10(-9)-3 x 10(-4) M) were enhanced in endothelium-denuded or N(G)-nitro-L arginine methyl- ester (L-NAME) (10(-5) M) pretreated rabbit aorta. The sensitivity, but not the maximal response, of both alpha1- and alpha2-adrenoceptor agonists was significantly lower at 28 degrees C (cooling) than at 37 degrees C. Endothelium removal did not affect the action of cooling. These results were taken as evidence for the specificity of alpha2-adrenoceptor agonists on the production and release of nitric oxide from vascular endothelium. The results suggest that the endothelium seems to have no role in the cooling-induced responses of both alpha1- and alpha2-adrenoceptors.     

Endothelial mediated enhancement of noradrenaline induced vasoconstriction in normal and varicose veins

Summary. The role of the endothelium to influence smooth muscle contraction in normal and varicose veins was investigated in vitro using saphenous vein preparations obtained at vascular surgery. Paired control and endothelium-denuded rings were tested simultaneously and contracted with noradrenaline (10^-9-10^-4 M). Identical experiments were also performed on sheep femoral veins and arteries. Noradrenaline induced maximal tension was 30% lower in varicose compared to normal veins. In normal veins removal of endothelium significantly reduced the maximal response to noradrenaline by 40% whereas in varicose veins no significant reduction could be seen. In the sheep femoral vein removal of the endothelium also resulted in decrease of noradrenaline-induced contraction. It can be concluded that in the human saphenous vein the endothelium has a contraction facilitating effect in response to stimulation with noradrenaline. In varicose veins the endothelial-mediated enhancement of noradrenaline-induced vasoconstriction is reduced probably because of endothelial damage. This observation may be of importance in the pathogenesis of varicose veins.     

Ca2+ mobilization in saphenous vein smooth muscle cells derived from patients with primary varicosity

BACKGROUND: Human primary varicosity is associated with 'weakness' of the vein wall. We investigated whether the reduced responsiveness of varicose veins to physiological vasoconstrictors might result from impaired Ca2+ mobilization in venous smooth muscle. MATERIALS AND METHODS: The hypothesis was tested in cells derived from phenotypically different vein segments that were obtained from the inguinal saphenous vein (tissue with incompetent valves), the distal portion of the long saphenous vein just above the medial ankle (clinically healthy tissue), and from a tributary to the long saphenous vein just below the knee (incompetent and overtly varicose tissue). Saphenous vein from patients undergoing cardiac surgery served as control. Cytosolic free Ca2+ levels ([Ca2+]i) were determined with the fura-2 method in cultured medial smooth muscle cells of third to sixth passage (21-23 measurements per tissue derived from five controls and seven patients). RESULTS: Angiotensin II (10 nmol L-1 to 10 mumol L-1) induced a significantly (P < 0.05) smaller rise in [Ca(2+)1i response in cells derived from incompetent or varicose segments (approximatley 70 nmol L-1) than in cells derived from clinically healthy vein (approximately 130 nmol L-1) or controls (approximately 170 nmol L-1). Likewise, the effect of endothelin-1 (100 nmol L-1) on [Ca2+]i was considerably less in cells derived from segments with incompetent valves or from varicose vessel segments than in cells derived from control patients (P < 0.05). In organ baths, endothelium-denuded strips of varicose vessels contracted significantly less in response to these agonists than clinically healthy segments from the same patient. CONCLUSIONS: The reduced contractility of diseased human varicose veins in response to angiotensin II and endothelin-1 involves impaired Ca2+ mobilization.     

Synergistic effects of ethanol and hyperthermia on carotid artery vasoconstriction

BACKGROUND: Heatstroke is a serious condition and clinical studies indicate that vascular stroke increases with excessive consumption of alcohol (ethanol). It was our objective to test the influence of ethanol on cerebral perfusion at normal and higher temperatures. METHODS: Recording of isometric tension in rabbit carotid artery strips in organ baths with different concentrations of ethanol at 37 degrees C and during hyperthermia (39-43 degrees C) and scintigraphic cerebral imaging of a radioactive isotope in the control situation and during hyperthermia. RESULTS: Stepwise heating induced reproducible reversible graded contraction, proportional to temperature. At high concentrations (toxic levels), ethanol induced an increase in tension and heating potentiated these responses. Extracellular Mg(2+) potentiated both heat-induced contraction and ethanol-induced contraction while extracellular Ca(2+) had no effect on these responses. During hyperthermia and ethanol scintigraphic isotope uptake was reduced in cortical and cerebellar regions. CONCLUSIONS: Carotid artery vasomotor tone is temperature dependent and heating induces vasoconstriction. Alcohol (ethanol) at 37 degrees C elicited carotid artery contraction at high concentrations (toxic levels) but at any concentration during elevated temperature (39-43 degrees C). Ethanol potentiated the effect of hyperthermia-induced vasoconstriction and reduced cerebral perfusion as shown by radionuclide imaging. The synergistic effect of ethanol and hyperthermia may induce heat stroke and brain damage.     

Alpha adrenergic responses of blood vessels of rabbits after ovariectomy and administration of 17 beta-estradiol

Experiments were designed to determine the effect of estrogen pretreatment on alpha adrenergic responsiveness of blood vessels of the rabbit. Rabbits were ovariectomized and, after 8 days of recovery, treated with 17 beta-estradiol (100 micrograms i.m.; estrogen group) or solvent (control group) for 4 days. Rings of saphenous vein and femoral artery (both without endothelium) were mounted for isometric tension recording in organ chambers filled with modified Krebs-Ringer bicarbonate solution (37 degrees C), gassed with 95% O2-5% CO2. All experiments were performed in the presence of inhibitors of neuronal uptake, extraneuronal uptake and beta adrenoceptors. In the saphenous vein, the estrogen treatment did not significantly affect the concentration-effect curves evoked by norepinephrine (either under control conditions or after alpha-1 or alpha-2 adrenergic blockade), phenylephrine (an alpha-1 adrenergic agonist) or UK 14,304 (an alpha-2 adrenergic agonist). In the femoral artery, estrogen treatment depressed the contractile responses evoked by norepinephrine (under control conditions) but not those produced by phenylephrine; UK 14,304 did not evoke a contractile response. The depressant effect of estrogen treatment on the concentration-effect curve to norepinephrine in the femoral artery was prevented by the alpha-2 adrenergic antagonist, rauwolscine. The results in the femoral artery but not in the saphenous vein suggest that estrogens depress alpha-2 but not alpha-1 adrenergic responsiveness. In the femoral artery, alpha-2 adrenoceptor stimulation does not cause contraction per se but apparently can facilitate alpha-1 adrenergic responses. This probably results from a reduced density of alpha-2 adrenoceptors in this blood vessel.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Alpha-1 and alpha-2 adrenoceptor: response coupling in canine saphenous and femoral veins

The aim of the present study was to analyze alpha-1 and alpha-2 adrenoceptor response coupling in isolated canine blood vessels. Rings of saphenous and femoral veins and of femoral arteries were suspended for isometric tension recording in modified Krebs-Ringer bicarbonate solution, gassed with 95% O2-5% CO2 and maintained at 37 degrees C. Dissociation constants for the alpha-1 adrenergic agonists, phenylephrine and cirazoline, and the alpha-2 adrenergic agonist, UK 14,304, were determined by analysis of concentration-effect curves to the agonists under control conditions and after partial inactivation of alpha adrenoceptors by phenoxybenzamine. The dissociation constant of phenylephrine for alpha-1 adrenoceptors in saphenous veins was approximately 10-fold higher than that obtained for the agonist in femoral arteries or femoral veins. Similarly the dissociation constant for cirazoline in the saphenous vein was higher than that obtained in other alpha-1 adrenergic systems. Dissociation constants were used to determine alpha adrenoceptor occupancy-response relationships. The alpha-1 adrenergic responses evoked by high intrinsic-efficacy agonists (cirazoline and phenylephrine) were associated with a very large receptor-reserve in the saphenous vein, but no, or only a limited receptor-reserve in the femoral vein. The dissociation constant for UK 14,304 in saphenous veins was significantly lower than that obtained for alpha-2 adrenergic stimulation by norepinephrine. There was no alpha-2 adrenoceptor reserve in the saphenous vein for these putative high intrinsic-efficacy agonists. The differences in receptor-reserve between alpha-1 adrenoceptors in canine saphenous and femoral veins and between alpha-1 and alpha-2 adrenoceptors in saphenous veins may help to explain the differential modulation of adrenergic responses in these blood vessels.     

Relation between density (maximum binding) of alpha adrenoceptor binding sites and contractile response in four canine vascular tissues

In microsomal fractions from dog aorta, saphenous veins, mesenteric arteries and veins, both [3H]prazosin and [3H]rauwolscine displayed monophasic saturation in binding. The Kd for [3H] rauwolscine binding was similar for all these blood vessels, but the maximum number of [3H]rauwolscine binding sites was 3 to 7 times higher in veins compared to arteries. The Kd for [3H] prazosin was higher in saphenous vein than that in the arteries. The maximum number of binding sites for [3H]prazosin was similar, except for that in aorta, which was 3 times greater. Phenylephrine (alpha-1 adrenoceptor selective agonist) or norepinephrine (nonselective adrenoceptor agonist) produced similar maximal responses in all vessels. The alpha-2 adrenoceptor selective agonist, B-HT 920 (2-amino-6-allyl-3,4,7,8-tetrahydro-6H-thiazolo[5,4-d]-azepine)-induced contraction in veins but not in arteries. Prazosin (10(-6) M) inhibited completely the contractions to norepinephrine (3 x 10(-6) M) in mesenteric arteries and to phenylephrine (3 x 10(-6) M) in arteries and veins. Contractile responses of mesenteric artery were unaffected by rauwolscine. Rauwolscine (10(-7) M) caused a greater parallel rightward shift of the concentration-response curve to norepinephrine than did prazosin (10(-7) M) in saphenous veins, and a further rightward shift of responses to norepinephrine after 10(-7) M prazosin in mesenteric vein and saphenous vein and abolished B-HT 920-induced responses at alpha-2 adrenoceptors. The tissues responding to B-HT-920 correspond to those having the highest alpha-2 receptor density as measured by [3H]rauwolscine binding. The density of such sites required for contraction to be initiated in veins was much higher than with alpha-1 adrenoceptor sites.(ABSTRACT TRUNCATED AT 250 WORDS)     

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)     

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.     

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.     

Effects of CRL 41034 on the adrenergic neuroeffector interaction in the canine saphenous vein

Experiments were designed to determine the effect of CRL 41034, a buflomedil analogue, on the adrenergic responsiveness of canine veins. Rings of saphenous vein (without endothelium) were suspended for isometric tension recording in modified Krebs-Ringer bicarbonate solution at 37 degrees C. CRL 41034 produced a concentration-dependent inhibition of the contractions evoked by the alpha adrenergic agonists norepinephrine, phenylephrine and UK 14304 which was insensitive to the blockade of neuronal uptake by cocaine. CRL 41034 was more potent in inhibiting the concentration-dependent contractions evoked by UK 14304 than those by phenylephrine and the antagonism it caused against the response to UK 14304 fulfilled the criteria for competitivity. CRL 41034, at 10(-5) M significantly depressed, and at 10(-4) M abolished the contractions induced by electrical stimulation of the adrenergic nerves and those evoked by the indirect sympathomimetic amine tyramine. Strips of canine saphenous vein were superfused after incubation with [3H] norepinephrine. During sympathetic nerve activation, CRL 41304 increased the stimulation-evoked overflow of [3H] norepinephrine and 3-methoxy-4-dihydroxyphenylglycol; in the presence of rauwolscine the compound only increased the stimulation-evoked overflow of 3,4-dihydroxyphenylglycol. These experiments suggest that the major vascular effects of CRL 41034 in canine veins are blockade of alpha 2-adrenoceptors on vascular smooth muscle, and inhibition of prejunctional alpha 2-adrenoceptors on adrenergic nerve endings.     

Flow cytometry study of polymorphonuclear neutrophil oxidative burst: a comparison of three fluorescent probes

BACKGROUND: The use of 2',7'-dichlorofluorescein diacetate (DCFH), dihydrorhodamine 123 (DHR) and hydroethidine (HE) has been described for detecting respiratory burst activity by flow cytometry in polymorphonuclear neutrophil (PMN) suspension. However, their specificities for reactive oxygen species are not well defined. We investigated the reactivity of these probes for detecting superoxide anion (O(2)(* -)), hydrogen peroxide (H(2)O(2)) and/or nitric oxide (NO(z.rad;))-dependent mechanisms. METHODS: PMNs (10(6)/ml) were preincubated for 15 min at 37 degrees C with DCFH (5 micro mol/l), DHR (1 micro mol/l) or HE (10 micro mol/l). Cell suspensions were then split for each probe into five different aliquots containing either no effector or one effector: N-ethylmaleimide (NEM, 150 micro mol/l, NADPH oxidase inhibitor), sodium azide (NaN(3), 50 micro mol/l, peroxidase and catalase inhibitor), N-nitro-L-arginine methyl ester (L-NAME, 1.5 micro mol/l, NO(z.rad;) synthase inhibitor) or H(2)O(2) (30%). At the same time, PMNs were stimulated with phorbol myristate acetate (PMA, 10 micro mol/l) for 10 min at 37 degrees C. Analyses were carried out on a Beckman-Coulter Epics XL equipped with an argon laser (488 nm). Green fluorescences from DCFH and DHR were measured in the FL1 channel and HE fluorescence was analyzed in the FL2 channel. RESULTS: NaN(3) decreased the fluorescence of PMNs incubated with DCFH, indicating that it needs a peroxidase activity to react with H(2)O(2). L-NAME reduced the oxidation of DCFH, showing that it reacts with reactive nitrogen species. DHR was specifically responsive to H(2)O(2) accumulation. HE seemed to be preferentially oxidized by O(2)(* -). CONCLUSIONS: Hence the choice of the probe to be used depends on the reactive species of interest.     

Pharmacologic characterization of human and canine thromboxane A2/prostaglandin H2 receptors in platelets and blood vessels: evidence for different receptors

The present study was undertaken to characterize thromboxane A2/prostaglandin H2 (TXA2/PGH2) receptors in platelets and blood vessels. Both human and canine platelet aggregation and saphenous vein contractions were induced by the stable TXA2/PGH2 mimetics (15S)-hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5Z, 13E-dienoic acid (U46619) and 9,11-epithio-11,12-methano-TXA2 (ONO-11113). ONO-11113 was a more potent agonist than U46619 in the human saphenous vein but less potent in the platelet. These agonists were equipotent in the canine platelet but ONO-11113 was more potent in the saphenous vein. Platelet aggregation and saphenous vein contraction induced by U46619 were blocked in a dose-dependent manner by the TXA2/PGH2 receptor agonists 9,11-dimethylmethano-11,12-methano-16-phenyl-13,14-dehydro-13-aza- 15 alpha beta-omega-tetranor-TXA2 (ONO-11120), 9,11-dimethylmethano-11,12-methano-16-(4-hydroxyphenyl)-13,14-d ihy dro-13-aza-15 alpha beta-omega-tetranor-TXA2 (PTA-OH), 9,11-dimethylmethano-11,12-methano-16-(4-methoxyphenyl)-13,14-d ihy dro-13-aza-15 alpha beta-omega-tetranor-TXA2 (PTA-OM), 9,11-dimethylmethano-11,12-methano-16-(3-iodo-4-hydroxyphenyl-13,1 4-dihydro-13- aza-15 alpha beta-omega-tetranor-TXA2 (I-PTA-OH) and 9,11-dimethylmethano-11,12-methano-15-phenyl-13,14-dihydro-13-aza- 15 alpha beta-omega-pentanor-TXA2 [PTA-(omega-1)].(ABSTRACT TRUNCATED AT 250 WORDS)     

Alpha adrenoceptor subtypes and receptor reserve in human versus canine saphenous vein: sensitivity to blockade by nitroglycerin

The purpose of this investigation was to determine the subtypes of alpha adrenoceptors present in human saphenous vein and to determine if there is a large receptor reserve for phenylephrine as has been demonstrated in canine saphenous vein. The subtypes of alpha adrenoceptors found in isolated human saphenous vein were determined using selective alpha-1 and alpha-2 adrenoceptor agonists and antagonists. Prazosin, a selective alpha-1 antagonist, produced a parallel shift of the concentration response curve to phenylephrine, a selective alpha-1 agonist, with no significant reduction in the maximal response. Yohimbine, a selective alpha-2 antagonist, produced a parallel shift of the concentration response curve to B-HT 920, a selective alpha-2 agonist, with no reduction in the maximal response. The pA2 values obtained for prazosin and yohimbine in human saphenous vein agreed closely with corresponding values obtained in canine saphenous vein. These results demonstrate that both alpha-1 and alpha-2 adrenoceptors exist in human saphenous vein. Phenoxybenzamine (10(-7) M), an irreversible alpha-1 adrenoceptor antagonist, markedly reduced the maximal response produced by phenylephrine, an agonist with high intrinsic activity, with no significant shift in the concentration response curve in human saphenous vein, suggesting that there was little or no alpha-1 receptor reserve for phenylephrine. The sensitivity of alpha-1 versus alpha-2 adrenoceptor-mediated vasoconstrictor responses to nitroglycerin were compared in human and canine saphenous veins. In both species, nitroglycerin blocked the vasoconstrictor response produced by stimulation of alpha-2 adrenoceptors to the same degree.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

A new protective solution for hypothermic storage of free vein grafts in cardiovascular surgery.

In order to reduce the operative injury of the endothelium in free reversed vein grafts, cultured human endothelial cells were used to test the optimal concentration of the constituents of a flushing solution for improved protection of the endothelium. The following solution proved to be the most suitable when tested at 20 degrees C; mannitol 160 mmol l-1, glucose 15 mmol l-1, NaCl 30 mmol l-1, KHCO3 5 mmol l-1, K2SO4 10 mmol l-1, KH2PO4 4 mmol l-1, MgSO4 20 mmol l-1, CaCl2 1.5 mmol l-1, potassium citrate 1.0 mmol l-1, Pluronic F-68 20 mg l-1, HEPES 4 mmol l-1, HEPES-Na 6 mmol l-1, pH 7.25, osmolality 325 mosmol kg-1 H2O. When endothelial cell injury was measured by a 51Cr-release assay, the new solution protected human endothelial cells in culture during hypothermic incubation better than isotonic NaCl, St Thomas' cardioplegic solution or Krebs-Henseleit's buffer. Transmission and scanning electron microscopy showed that the endothelium of human saphenous vein grafts was well preserved following 6 h of incubation at 20 degrees C with the new solution. As determined by morphometry using scanning electron microscopy, the endothelium of free porcine vein grafts was better preserved after incubation for 2 h at 20 degrees C with the new solution than with either isotonic NaCl (p = 0.02) or diluted, heparinized blood (p = 0.02) as the incubation medium, all cases observed following 2 h of subsequent arterial flow. The present study indicates that the endothelium of free vein grafts can be well protected against hypothermia when the flushing and irrigation fluid has a composition favouring endothelial protection. It appears likely that such treatment of vein grafts will reduce the frequency of vein graft narrowing and occlusion, post-operatively.