Human Gastroepiploic Artery Research Articles

Impact of cigarette smoking on nitric oxide-sensitive and nitric oxide-insensitive soluble guanylate cyclase-mediated vascular tone regulation.

Cigarette smoking induces vascular endothelial dysfunction characterized by impaired nitric oxide (NO) bioavailability. There are two types of soluble guanylate cyclase (sGC), which is a cellular target of NO: NO-sensitive reduced form (the heme moiety with a ferrous iron) and NO-insensitive oxidized (the heme moiety with a ferric iron)/heme-free form. This study investigated the influence of cigarette smoking on NO-sensitive and NO-insensitive sGC-mediated vascular tone regulation in organ chamber experiments with isolated rat and human arteries. The rats were subcutaneously administered phosphate-buffered saline (PBS), nicotine-free cigarette smoke extract (N(-)-CSE) or nicotine-containing cigarette smoke extract (N(+)-CSE) for 4 weeks. Plasma thiobarbituric acid reactive substance (TBARS) levels were higher in the N(+)-CSE group than those in the N(-)-CSE group, and TBARS levels for these groups were higher than those for the PBS group. In the aorta and the pulmonary artery in rats administered N(-)-CSE or N(+)-CSE, acetylcholine-induced relaxation was significantly impaired compared with that in rats administered PBS; there was no significant difference in the relaxation between the N(-)-CSE and N(+)-CSE groups. However, sodium nitroprusside (NO-sensitive sGC stimulant)- and BAY 60-2770 (NO-insensitive sGC stimulant)-induced relaxations were not different among the three groups, regardless of the vessel type. In addition, in the human gastroepiploic artery, the relaxant responses to these sGC-targeting drugs were identical between nonsmokers and smokers. These findings suggest that NO-sensitive and NO-insensitive sGC-mediated vascular tone regulation functions normally even in blood vessels damaged by cigarette smoking.

G-Protein-gated Inwardly-Rectifying K+ Channels and Large-conductance Calcium-Activated K+ Channels Are Involved in C-Type Natriuretic Peptide-Mediated Vasodilation in Human Arteries.

C-type natriuretic peptide (CNP) hyperpolarizes and relaxes the smooth muscle of blood vessels. We investigated whether G-protein-gated inwardly-rectifying K+ channels (GIRK) and large-conductance calcium-activated K+ channels (BKCa channels) were involved in CNP-evoked vasodilatation in human arteries. Isometric tension in human gastroepiploic arteries was measured using a wire myograph. Ion channel currents were recorded by the whole-cell patch-clamp technique. The concentration-dependent vasodilation induced by CNP was reduced significantly after inhibition of GIRK channels (by tertiapin-Q) or of BKCa channel (by paxilline). Immunochemical experiments showed that GIRK3 and GIRK4 subunits were expressed in human arteries. CNP also strongly increased the current density of GIRK and BKCa channels in human arterial smooth muscles. This suggested that the GIRK channel was functionally expressed in smooth muscle and vasodilation action was produced by CNP partly by opening the GIRK and BKCa channels in the human artery.

OS 02-06 PHYSIOLOGICAL REGULATION OF VASOMOTION BY INTRACELLULAR ATP-MEDIATED SYSTEM IN HUMAN ARTERY.

Spontaneous oscillation of tone of blood vessel called vasomotion cause vessel to flow blood which is an oscillation of flow into an organ. Microcirculation is sensitive to hypoxic condition and metabolism but mechanism of vasomotion is still poorly understood. Purpose: We studied involvement of metabolism-mediated regulation by intracellular ATP level of vasomotion in human gastric artery. Conventional contractile measuring system and Western blot were used. Circular muscle of human gastric artery produced sustained tonic contraction of 1.0 ± 0.19 g by 50 mM high K (n = 36). Pinacidil (10 μM), which is known to activatorof ATP-sensitive K (KATP) channel inhibited vasomotion completely in a reversible manner. Inhibition of vasomotion by activators of KATP channel recovered by glibenclamide. Diazoxide (300 μM), cromakalim (10 μM) nicorandil (10 μM) which is known to activate KATP channel also completely blocked vasomotion in a glibenclamide sensitive manner. Inhibitory effect of these openers of KATP channel on serotonin and norepinephrine-induced contraction were also recoded in a glibenclmide-sensitive manner. In human artery, glucose-free condition which is elated metabolic changes inhibited vasomotion and it was recovered by glibenclamide. Finally, molecular subtypes of KATP channel was defined by Western blot in human artery. Vasomotion of human gastroepiploic artery was inhibited by activation of specific subtypes of KATP channel and alteration of metabolism.

Reduction of vasoconstriction by removing periarterial nerve in human gastroepiploic artery imply prevention of vasospasm

BackgroundThe right gastroepiploic artery (GEA) is used as an in‐situ arterial graft for coronary artery bypass grafting (CABG). However, the GEA is more likely to cause vasospasms compared to the internal thoracic artery. We hypothesized that the significant cause of GEA spasms is triggered by periarterial sympathetic nerve, since the GEA is classified as a muscular artery.Materials and MethodsUnused parts of the GEA were obtained from patients who underwent CABG. The vessel was assigned to control (N+) and denervation (N−) group. For N− group, periarterial nerve was microscopically removed. These vessels were investigated by hematoxylin‐eosin (H‐E) and immunohistochemical staining. Then, each vessel was exposed to electrical field stimulation (EFS).ResultsHistological analysis revealed that the periarterial connective tissues including neuropeptide Y (NPY) were removed from lateral layer to external elastic membrane in the N−, whereas they were preserved in N+. The vasoconstriction by EFS with serial frequency was consistently lower in N− than N+ (p<0.05 at 20 and 50Hz; n=8 each). These vasoconstrictions were inhibited by tetrodotoxin. Moreover, endothelium dependent relaxation and vasoconstriction of the smooth muscle were similar in both groups.ConclusionsThe removal of periarterial nerves from human GEA can prevent graft spasms without disturbance of endothelial and smooth muscle functions.

Denervation of gastroepiploic artery graft can reduce vasospasm

The right gastroepiploic artery is useful as an in situ arterial graft for coronary artery bypass grafting. However, the gastroepiploic artery is more likely to cause vasospasms compared with the internal thoracic artery. We hypothesized that the cause of the spasms is the stimulation of the periarterial sympathetic nerve, because the gastroepiploic artery is classified as a muscular artery. In this study, we examined whether the spasm is reduced by removing the periarterial sympathetic nerve. Unused parts of the gastroepiploic artery were obtained from patients who underwent coronary artery bypass grafting. The vessel was cut into 2 segments, and they were assigned to control (N+) and denervation (N-) groups. The periarterial nerve was microscopically removed from the vessels of the N- group. The vessels in both groups were investigated by hematoxylin-eosin or immunohistochemical staining, and they were stimulated by electrical field stimulation with serial frequency for isometric tension measurement. Histologic analyses revealed that periarterial connective tissues including neuropeptide Y were removed to expose the external elastic membrane in the N- vessel, whereas they were preserved in N+. The mean contraction by electrical field stimulation with serial frequency was consistently lower in N- than in N+ (P<.05 at 20 and 50 Hz; n=8 each). Endothelium-dependent relaxation and contractile function of the smooth muscle were similar in both groups. The removal of the periarterial sympathetic nerve from the human gastroepiploic artery reduced vascular contraction, elicited by peripheral nerve stimulation, without disturbing endothelial and smooth muscle contractile functions. This reduction may contribute to the prevention of vasospasms.

Dexmedetomidine does not produce vasocontraction on human isolated gastroepiploic artery

BackgroundRecently, the addition of dexmedetomidine to sedation regimens after cardiac surgery had been reported and there is a possibility that dexmedetomidine can cause vasoconstriction. Vasopressin has been used as a prophylactic treatment for refractory vasodilatory shock during coronary artery bypass graft (CABG). Also, vasopressin may play an important role in initiating spasms at the graft artery. Here we evaluate the direct effect of dexmedetomidine on isolated human gastroepiploic arteries and the synergistic effect of dexmedetomidine and vasopressin.MethodsDiscarded gastroepiploic arteries from elective subtotal gastrectomy (n = 10) were used in this study. We measured the level of contraction in isolated human gastroepiploic arteries induced by increasing concentrations of dexmedetomidine (10-10 to 10-6 M) with or without vasopressin (10-10, 10-9 M). Arterial contractions caused by increasing concentrations of vasopressin (10-10 to 10-7.5 M) with or without dexmedetomidine (10-9, 10-7 M) were also measured in the tissue samples.ResultsSupraclinical concentrations of dexmedetomidine elicited contractions at concentrations of 10-7 M and 10-6 M (P < 0.05 versus resting tension). The same concentrations of dexmedetomidine (10-7, 10-6 M) significantly enhanced vasopressin-induced contractions (P < 0.05 versus vasopressin-induced contraction). Vasopressin produced concentration-dependent contractions and vasopressin (10-10, 10-9.5, 10-9 M) also increased the intensity of dexmedetomidine (10-7 M) induced contractions.ConclusionsThere was a synergistic effect between supraclinical doses of dexmedetomidine and vasopressin on the degree of contraction in isolated human gastroepiploic arteries. However, a sedative dose of dexmedetomidine (clinical dose: 0.2-0.7 µg/kg/hr, plasma concentration: 0.36-1.25 ng/ml) did not enhance vasopressin induced-contraction in isolated human gastroepiploic arteries.

Effects of a Novel Benzodiazepine Derivative, JM-1232(-), on Human Gastroepiploic Artery In Vitro

To investigate the effects of JM-1232(-) on norepinephrine (10(-6) mol/L)- and high K(+) (40 mmol/L)-induced contractions in isolated human gastroepiploic arteries (GEA), and to compare them with the effects of midazolam and propofol. In addition, to investigate whether the benzodiazepine-receptor antagonist, flumazenil, or μ-opioid-receptor antagonist, naloxone, influenced the vascular effects of JM-1232(-). An in vitro experimental study. University laboratory. GEA segments were used from 69 patients undergoing coronary artery bypass graft surgery. JM-1232(-) produced dose-dependent relaxation effects in the rings. Although these effects of JM-1232(-) were greater than those of midazolam and propofol at high concentrations (10(-5)-10(-4) mol/L), there were no significantly different relaxation effects at the clinical concentrations of 3 × 10(-6) mol/L JM-1232(-), 3 × 10(-6) mol/L midazolam, and 1 × 10(-5) mol/L propofol. In addition, all these effects were independent of the presence of a functional endothelium. Vasorelaxation induced by JM-1232(-) on norepinephrine-preconstricted GEA was inhibited by flumazenil, but not by naloxone. These results indicate that JM-1232(-) dose-dependently relaxes smooth muscle in human GEA, this effect being independent of the endothelium. Within the ranges of plasma concentrations achieved in clinical practice, JM-1232(-) had similar vasorelaxation effects to midazolam and propofol. JM-1232(-)-induced vasorelaxation was inhibited by flumazenil, indicating that JM-1232(-)-induced vasorelaxation occurred via peripheral benzodiazepine receptor activation in the GEA.

NF‐κB activation stimulates osteogenic differentiation of mesenchymal stem cells derived from human adipose tissue by increasing TAZ expression

Tumor necrosis factor-alpha (TNF-alpha) is a skeletal catabolic agent that stimulates osteoclastogenesis and inhibits osteoblast function. Although TNF-alpha inhibits the mineralization of osteoblasts, the effect of TNF-alpha on mesenchymal stem cells (MSC) is not clear. In this study, we determined the effect of TNF-alpha on osteogenic differentiation of stromal cells derived from human adipose tissue (hADSC) and the role of NF-kappaB activation on TNF-alpha activity. TNF-alpha treatment dose-dependently increased osteogenic differentiation over the first 3 days of treatment. TNF-alpha activated ERK and increased NF-kappaB promoter activity. PDTC, an NF-kappaB inhibitor, blocked the osteogenic differentiation induced by TNF-alpha and TLR-ligands, but U102, an ERK inhibitor, did not. Overexpression of miR-146a induced the inhibition of IRAK1 expression and inhibited basal and TNF-alpha- and TLR ligand-induced osteogenic differentiation. TNF-alpha and TLR ligands increased the expression of transcriptional coactivator with PDZ-binding motif (TAZ), which was inhibited by the addition of PDTC. A ChIP assay showed that p65 was bound to the TAZ promoter. TNF-alpha also increased osteogenic differentiation of human gastroepiploic artery smooth muscle cells. Our data indicate that TNF-alpha enhances osteogenic differentiation of hADSC via the activation of NF-kappaB and a subsequent increase of TAZ expression.

Skeletonization with an ultrasonic scalpel is as safe as a non-skeletonized dissection in preserving the endothelial function of the human gastroepiploic artery

The right gastroepiploic artery (GEA) is frequently used as another in situ artery, other than the internal thoracic artery (ITA) in coronary artery bypass grafting (CABG). Skeletonizing the graft with an ultrasonic scalpel is now regarded as a useful technique; however, this technique may damage the endothelial function during harvesting the graft resulting in postoperative graft stenosis or occlusion. In the present study, GEA segments from nine patients were excised in both a skeletonized and non-skeletonized manner with an ultrasonic scalpel, and then were transported to the laboratory. The vessels were trimmed as rings, and were allotted to the group of skeletonized or non-skeletonized, accordingly. The force development in response to 1 mumol/l norepinephrine did not differ between the skeletonized and non-skeletonized groups. Endothelium-dependent relaxation induced by either acetylcholine or bradykinin was not impaired in the skeletonized group in comparison to the non-skeletonized group. No significant difference was observed in endothelium-independent relaxation elicited by sodium nitroprusside. Therefore, the skeletonization of the GEA with an ultrasonic scalpel was thus found to be as safe as a non-skeletonized dissection in preserving the vascular contractile ability or endothelium-dependent and -independent relaxation of the graft.

Effects of propofol on vasopressin-induced vasoconstriction in isolated human gastroepiploic artery

Effects of propofol on vasopressin-induced vasoconstriction in isolated human gastroepiploic artery

Effects of Propofol on Arginine Vasopressin-induced Contraction in Isolated Human Gastroepiploic Artery

Arginine vasopressin has been used by prophylactic treatment of vasodilatory shock during coronary artery bypass graft (CABG). Vasopressin may be a cause of spasm in graft artery during CABG. We evaluated the effect of propofol on vasopressin-induced contraction in human gastroepiploic artery (GEA). Methods: Human GEA were obtained from 35 patients (43−74 yr), undergoing subtotal gastrectomy. Vasopressin-induced a concentration contractions (10−9 to 10−6 M) were measured after exposed to without propofol, propofol 10−5, 10−4, 10−3 M. After endothelium denuding vasopressin-induced a concentration contractions were measured with or without propofol 10−3 M in calcium free solution. In the denuded vascular rings, with or without pretreatment of glibenclamide (10−5 M), nicorandil (10−5 M), or diltiazem (10−5 M) were exposed to with or without propofol 10−3 M, and vasopressin-induced concentration contractions were measured. Results: Vasopressin-induced concentration contraction on human GEA was independent of functional endothelium. Propofol (10−4, 10−3 M) attenuated the vasopressin-induced contraction in the human GEA. Diltiazem attenuated the vasopressin-induced contraction in the human GEA. ATP-sensitive potassium channel does not affect the inhibition effect of propofol on vasopressin-induced contraction Conclusions: Usual anesthetic dose of propofol does not inhibit vasopressin-induced contraction on human GEA. High dose (＞10−4 M) propofol attenuated vasopresssi-induced contraction on GEA.

Effects of aspirin, nimesulide, and SC-560 on vasopressin-induced contraction of human gastroepiploic artery and saphenous vein*

The present experiments were designed to evaluate differences in the effects of cyclooxygenase (COX)-1 and COX-2 inhibition on contractile responses of human gastroepiploic artery and saphenous vein elicited by vasopressin. Laboratory investigation. University laboratory. Rings of human gastroepiploic artery were obtained from 32 patients undergoing gastrectomy, and rings of saphenous vein were obtained from 30 patients undergoing coronary artery bypass surgery. The rings were suspended in organ baths for isometric recording of tension. We studied the responses to vasopressin in the absence and in the presence of either the vasopressin V1-receptor antagonist d(CH2)5Tyr(Me)AVP or the COX inhibitors aspirin, nimesulide, or SC-560. Vasopressin (10(-11)-10(-6) mol/L) produced concentration-dependent contractions with an EC50 value of 4.3 x 10(-10) mol/L for gastroepiploic artery and 3.4 x 10(-8) mol/L for saphenous vein. The vasopressin V1-receptor antagonist d(CH2)5Tyr(Me)AVP (10(-7) mol/L) induced significant shifts (p < .001) of the control curves to the right. The COX-1 and COX-2 inhibitor aspirin (10(-6)-10(-5) mol/L) and the COX-2 inhibitor nimesulide (10(-6) mol/L) induced leftward shifts of the concentration-response curve for vasopressin in gastroepiploic artery. Lower concentrations of aspirin or the COX-1 inhibitor SC-560 (10(-8) mol/L) did not affect the responses of gastroepiploic artery. COX-1 or COX-2 inhibition did not modify the contraction of saphenous vein to vasopressin. The results provide functional evidence that aspirin at high concentrations and the COX-2 selective inhibitor nimesulide potentiate the contractile response of gastroepiploic artery to vasopressin, thus suggesting the release of relaxant prostaglandins by the peptide. However, contractions of human saphenous vein were unaffected by COX inhibition, indicating that vasopressin does not stimulate the release of prostanoids. The amplifying effect of aspirin on vasopressin-induced contraction may contribute to early graft failure when the gastroepiploic artery is used as a coronary artery bypass graft.

Aspirin and COX-2 Inhibitor Nimesulide Potentiate Adrenergic Contractions of Human Gastroepiploic Artery

The aim of the present study was to evaluate the intervention of COX-1- and COX-2-derived prostaglandins in the responses of human gastroepiploic artery to sympathetic stimulation and norepinephrine. Rings of human gastroepiploic artery were obtained from 45 patients (26 men and 19 women) undergoing gastrectomy. The rings were suspended in organ baths for isometric recording of tension. We studied the responses to electrical field stimulation, norepinephrine, and acetylcholine, in the absence and presence of COX-1 or COX-2 inhibition. The COX-1 and COX-2 inhibitor aspirin at high concentrations (10(-6) to 10(-5) mol/L) and the COX-2 inhibitor nimesulide (10(-6) mol/L) potentiated the contractile responses of the arterial rings to sympathetic neurogenic stimulation and norepinephrine. In contrast, lower concentrations of aspirin (10(-8) to 10(-7) mol/L) or the COX-1 inhibitor SC-560 (3 x10(-8) mol/L) did not affect these responses. The vascular relaxation induced by acetylcholine was not affected by COX-1 and COX-2 inhibition. The results provide functional evidence that vasodilator prostaglandins are active components of the response of human gastroepiploic artery to neurogenic stimulation and norepinephrine. Aspirin at high concentrations and the COX-2 selective inhibitor nimesulide potentiated the contractile response of gastroepiploic artery to adrenergic stimulation by inhibiting COX-2-derived PGI(2). Aspirin at low concentrations and the COX-1 selective inhibitor SC-560 did not modify the contractile responses, possibly due to minor importance of vasoconstrictor prostaglandins (TXA(2)) as active components of the response of gastroepiploic artery to adrenergic stimulation.

Human gastroepiploic artery has greater chymase activity than the internal thoracic artery

Recent reports have demonstrated that long-term patency of the gastroepiploic artery (GEA) in coronary artery bypass grafting (CABG) is less satisfactory compared with the internal thoracic artery (ITA). However, the reason has not been fully elucidated. Angiotensin II is known to play an important role in the development of intimal hyperplasia, we hypothesized that the GEA is different from the ITA with respect to angiotensin II-forming ability. Accordingly, we measured activities of angiotensin II-forming enzymes, angiotensin-converting enzyme (ACE) and chymase, in human GEA and ITA. Remnant of the GEAs and ITAs were obtained from 24 patients who underwent CABG in which both conduits were used simultaneously. Activities of ACE and chymase were measured by using the extract form the GEA or ITA. Sections of the GEA or ITA were immunohistochemically stained with anti-human chymase antibody. The ACE activity of the GEA (0.28+/-0.16 mU/mg protein) was greater than that of the ITA (0.18+/-0.11, p < 0.001). The chymase activity of the GEA (11.11+/-7.15 mU/mg protein) was also greater than that in the ITA (7.13+/-4.89, p < 0.001). The density of chymase-positive cells in the GEA (3.8+/-4.2 cells/mm2) was greater than that in the ITA (1.1+/-1.2, p < 0.01). Activities of both ACE and chymase were significantly greater in the GEA compared with the ITA. The GEA may be different from the ITA with respect to potential ability of angiotensin II-formation.

Effects of a phosphodiesterase 3 inhibitor, olprinone, on rhythmical change in tension of human gastroepiploic artery

The gastroepiploic artery, used widely as a conduit in coronary artery bypass grafting, has high vasospasticity. The aims of this study were to examine the vasorelaxant effects of three phosphodiesterase 3 (PDE3) inhibitors, olprinone, milrinone and amrinone, on isolated gastroepiploic arterial preparations in comparison with a calcium channel blocker diltiazem, and to confirm the mRNA expression of PDE3A isoenzyme using reverse transcription–polymerase chain reaction (RT-PCR) in the human gastroepiploic artery isolated from stomach removed in cancer surgery. In endothelium-denuded gastroepiploic arterial preparations, phenylephrine (100 μM) produced spontaneous, rhythmical changes in tension consisting of repeated contraction and relaxation. Olprinone at a concentration of 10 μM ( n = 6) significantly inhibited the frequency (2.7 ± 1.1 times/30 min vs. 6.2 ± 0.7 times/30 min in the vehicle group), maximum tension (1.7 ± 0.6 g vs. 3.6 ± 0.6 g in the vehicle group) and minimum tension (0.6 ± 0.2 g vs. 1.7 ± 0.3 g in the vehicle group) of rhythmical changes. Such potency is comparable to that of diltiazem, but is stronger than milrinone and amrinone. RT-PCR using PDE3A- or PDE3B-specific oligonucleotide primer demonstrated the existence of PDE3A sequence in the gastroepiploic artery. These results suggest that olprinone, a potent PDE3A inhibitor, would be suitable for protecting against perioperative spasm during coronary artery bypass graft surgery.

Differential Pharmacologic Sensitivities of Phosphodiesterase-3 Inhibitors Among Human Isolated Gastroepiploic, Internal Mammary, and Radial Arteries

Systematic investigations of the actions of phosphodiesterase (PDE)-3 inhibitors on different human vascular tissues have not been performed. We investigated the effects of specific PDE-3 inhibitors (olprinone, milrinone, and amrinone) on contracted human gastroepiploic arteries (n = 70), internal mammary arteries (n = 72), and radial arteries (n = 70) harvested from a total of 134 patients, all of whom were undergoing coronary artery bypass surgery. Each of these PDE-3 inhibitors dose-dependently diminished the contractile responses to 10(-6) mol/L norepinephrine and to either 10(-9) or 10(-8) mol/L of the thromboxane A2 analog U46619. In inducing vasorelaxations, these inhibitors were significantly more potent in norepinephrine-contracted rings than in those contracted with U46619. Further, at concentrations similar to the maximum therapeutic plasma concentrations (10(-7) mol/L olprinone; 10(-6) mol/L milrinone; 10(-5) mol/L amrinone) olprinone and milrinone were more potent at inducing relaxations than amrinone in gastroepiploic arteries and radial arteries, whereas in internal mammary arteries milrinone was more potent than the others. These results suggest different activities for the three PDE-3 inhibitors among human arteries located in different regions and may be informative about the effectiveness of these inhibitors in preventing spasms in the various arterial grafts used in revascularization. Because three phosphodiesterase-3 inhibitors (milrinone, olprinone, and amrinone) differed in their vasodilator potencies (against the contractile response to either norepinephrine or a thromboxane A2 analog) among human arteries removed from different parts of the body, their vascular relaxation profiles should be considered before they are used clinically.

Neurogenic double‐peaked vasoconstriction of human gastroepiploic artery is mediated by both α1‐ and α2‐adrenoceptors

1. The contribution of postjunctional P2X receptors and subtypes of alpha-adrenoceptors to vasoconstrictor responses following periarterial electrical nerve stimulation (PNS, 30 s trains of pulses at a frequency of 2, 4 or 8 Hz) was investigated in human gastroepiploic arteries. 2. The vasoconstrictor response to PNS at a stimulation of 4 or 8 Hz was a two-peaked response, whereas at a frequency of 2 Hz it appeared only as a late peak. All vasoconstrictions evoked by PNS were abolished by phentolamine, a nonselective alpha-adrenoceptor inhibitor, but not by alpha,beta-methylene ATP, a P2X receptor-desensitizing agent. 3. The early peak to PNS at 4 or 8 Hz was abolished by prazosin, an alpha1-adrenoceptor antagonist, while the late one still remained, although it was markedly inhibited. The responses remaining after prazosin were blocked by rauwolscine. The vasoconstrictor response to PNS at 2 Hz was not affected by prazosin (0.1 microM), but was abolished by rauwolscine (0.1 microM), an alpha2-adrenoceptor antagonist. 4. OPC-28326 (10 microM), a newly developed vasodilator, which preferentially exerts its antagonistic actions on the alpha2B- and alpha2C-adrenoceptors, significantly reduced the noradrenaline-induced vasoconstriction in the absence or presence of prazosin. OPC-28326 had a greater inhibitory effect on the late peak evoked by PNS than the early one. The neurogenic responses remaining after OPC-28326 were abolished by prazosin. 5. The present results suggest that sympathetic vasoconstriction of the human gastroepiploic artery is mediated by both alpha1- and alpha2-adrenoceptors postjunctionally, but not by P2X receptors. The alpha2-adrenoceptors may be preferentially activated at a low frequency of stimulation, which induces a constriction more slowly than that by alpha1-adrenoceptors. The existence of alpha2-adrenoceptors may cause an enhancement of alpha1-adrenoceptor-induced responses.

Existence of alpha-adrenoceptor subtypes in isolated human gastroepiploic and omental arteries.

Establishing the existence of alpha-adrenoceptor subtypes in isolated human gastroepiploic and omental arteries was the goal of the present study. Functional vascular reactivity of selective alpha(1)- and alpha(2)-adrenoceptor agonists and antagonists was studied, using a cannula inserting technique. Intraluminal administration of norepinephrine (NE), phenylephrine (PE) or BHT-933 caused a vasoconstrictive response in a dose-related manner. The relative potencies of the 3 agonists were almost the same in both arteries. NE-induced vasoconstrictions were significantly antagonized by either prazosin or rauwolscine. PE-induced responses were strongly inhibited by prazosin. BHT-933-induced constrictions were inhibited by rauwolscine. These results indicate that both alpha(1)- and alpha(2)-adrenoceptors exist in the human gastroepiploic and omental arteries.

Influence of nitric oxide on neurogenic contraction and relaxation of the human gastroepiploic artery

BackgroundThe objective of this study was to characterize the neurogenic contraction and relaxation of the human gastroepiploic artery and to determine whether the responses are mediated by nitric oxide (NO) from neural or endothelial origin. MethodsRings of human gastroepiploic artery were obtained from 18 patients (12 men, 6 women) undergoing gastrectomy. The rings were suspended in organ baths for isometric recording of tension. We studied the contractile and relaxant responses to electrical field stimulation. ResultsIn arteries under resting conditions, electrical field stimulation (2 to 8 Hz) caused frequency-dependent contractions that were of greater magnitude in arteries denuded of endothelium and blocked by tetrodotoxin (10−6 mol/L). The inhibitor of NO synthesis NG-monomethyl-l-arginine (L-NMMA, 10−4 mol/L) increased contractile responses only in arteries with endothelium. In preparations contracted with norepinephrine in the presence of guanethidine (10−6 mol/L) and atropine (10−6 mol/L), electrical stimulation induced frequency-dependent relaxations. This neurogenic relaxation was prevented by L-NMMA (10−4 mol/L) and tetrodotoxin (10−6 mol/L), but was unaffected by removal of the endothelium. ConclusionsThe results provide functional evidence that NO is released by autonomic nerves of the human gastroepiploic artery. We hypothesize that the release of NO from both endothelial and neurogenic origin may modulate resistance of the human gastroepiploic artery. Dysfunction in any of these sources of NO should be considered in some form of vasospasm.

Dual alpha(2)-adrenergic agonist and alpha(1)-adrenergic antagonist actions of dexmedetomidine on human isolated endothelium-denuded gastroepiploic arteries.

The actions of dexmedetomidine (DEX) on human vascular smooth muscle are unclear. We investigated its effects on isolated, endothelium-denuded human gastroepiploic arteries in vitro and compared them with clonidine (CLO). DEX had little direct effect on resting tension, whereas CLO produced small contractile responses, an effect which is blocked by the alpha(1)-adrenergic antagonist prazosin. DEX markedly enhanced the high K(+) (40 mmol/L)-induced contraction, and this effect was reversed by the alpha(2)-adrenergic antagonists yohimbine and rauwolscine but unaffected by prazosin. However, CLO had little effect on the K(+) contractions. Interestingly, larger concentrations (>10(-7) mol/L) of both alpha(2)-adrenergic stimulants significantly inhibited the contractions elicited by the alpha(1)-adrenergic agonist phenylephrine (10(-6) mol/L) and, to a lesser extent, those elicited by the alpha(1)/alpha(2)-agonist norepinephrine (10(-6) mol/L). These results suggest the possibility that DEX and CLO each have a high affinity for alpha(1)-adrenoceptors in human isolated gastroepiploic arteries, resulting in a reduced efficacy of alpha(1)-adrenergic activation by alpha-agonists. The differing affinities of the drugs for alpha(1)- and alpha(2)-adrenoceptors may help explain their additional actions: 1) DEX enhances the high K(+)-induced contraction presumably through alpha(2)-adrenoceptor activation, and 2) CLO acts on alpha(1)-adrenoceptors as a partial agonist when present alone. Dexmedetomidine may not directly affect smooth muscle in human peripheral resistance vessels within the usual range of plasma concentrations (<10(-7) mol/L) achieved in clinical practice. However, in large doses, it could enhance the response to nonadrenergic vasoconstrictor agonists while antagonizing the vasoconstrictor response to alpha(1)-adrenoceptor agonists.