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S Jovanović

Publications and source records attributed to S Jovanović.

At least 19 recordsLinked to original sources
PubMed2001

Diadenosine tetraphosphate-gating of cardiac K(ATP) channels requires intact actin cytoskeleton.

Diadenosine polyphosphates (ApnA) have been recently discovered in the heart, and their levels found to be regulated by ischemia. These signaling molecules are believed to regulate cellular processes that alarm a cell to metabolic stress. In particular, changes in cardiac diadenosine polyphosphates (ApnA) levels may contribute to the regulation of ATP-sensitive K+ (K(ATP)) channel activity, an ion channel that couples the cellular metabolic state with membrane excitability. A feature of myocardial ischemia is the disruption of the actin cytoskeleton which critically regulates the behavior of K(ATP) channels. Whether the integrity of actin microfilaments regulates the interaction of ApnA with K(ATP) channels is not known. The inside-out configuration of the patch-clamp technique was applied to cardiomyocytes isolated from guinea-pig heart. Following patch excision, the prototype dinucleotide, diadenosine tetraphosphate (Ap4A), inhibited K(ATP) channel opening. Treatment of the internal side of membrane patches with either cytochalasin B or DNase I, disrupters of the actin cytoskeleton, prevented Ap4A-induced inhibition of K(ATP) channel opening. Application of purified actin to DNase-treated membrane patches restored the ability of Ap4A to close K(ATP) channels. This study shows that inhibition of cardiac K(ATP) channel by Ap4A, a putative alarmone, requires intact subsarcolemmal actin network. Such interaction between K(ATP) channels, the cardiomyocyte cytoskeleton and intracellular Ap4A could affect different channel-dependent functions.

Actins↗
PubMed2001

Minimal fixation in the treatment of open hand and foot bone fractures caused by explosive devices: case series.

AIM: To evaluate minimal fixation method with Kirschner's wires in the treatment of open fractures of the hand and foot short bones, caused by explosive devices. METHOD: There were 270 wounded persons with open fractures of hand and foot short bones, who were surgically treated at the Department of Surgery at the Osijek University Hospital. The stabilization of an unstable open fracture was performed with intramedullary positioned Kirschner's wires. In a few cases, satisfactory stabilization was achieved with Kirschner's wires positioned percutaneously alongside the wound and perpendicularly through the fracture. In the rest of the wounded, plaster immobilization was sufficient after surgical treatment and fracture reposition. RESULTS: Among 270 persons with 412 open hand and foot bone fractures, 49% had fracture only in the feet, 27% only in the hands, and 24% in both hands and feet. Unstable short bone fractures were found in 56 patients (21%). Such fractures were stabilized with Kirschner's wires (n=71). In 58 patients (21%) partial hand and foot amputations had to be performed. Reconstructive operations to improve pseudarthrosis after minimal osteosynthesis were performed on 5 short bones (7%). Osteitis was found on four short bones (6%) after minimal osteosynthesis. CONCLUSION: Minimal osteosynthesis with Kirschner's wires is a reliable and adequate method of the treatment of open unstable short bone fractures caused by explosive devices.

Blast Injuries↗
PubMed2000

Low concentrations of 17beta-estradiol protect single cardiac cells against metabolic stress-induced Ca2+ loading.

OBJECTIVES: The main objective of the present study was to determine whether low physiological levels of estrogen directly protect cardiac cells against metabolic stress. BACKGROUND: The beneficial effect of estrogens on the cardiovascular system has been traditionally ascribed to decrease in peripheral vascular resistance and to an antiatherogenic action. Whether physiological concentrations of 17beta-estradiol (E2) are also able to protect cardiomyocytes against metabolic insult directly is unknown. METHODS: Isolated ventricular cardiomyocytes were loaded with the Ca2+-sensitive fluorescent dye Fluo-3 and imaged by a digital epifluorescence imaging system. In cardiac cells preincubated with hormones and/or drugs for 8 h, metabolic stress was induced by addition and removal of 2,4-dinitrophenol (DNP). RESULTS: In cardiomyocytes, a 3-min-long exposure to chemical hypoxia, followed by reoxygenation, produced intracellular Ca2+ loading independently of gender (female: 729 +/- 88 nmol/liter; male: 778 +/- 97 nmol/liter). Pretreatment with E2 (10 nmol/liter) significantly reduced the magnitude of hypoxia/reoxygenation-induced Ca2+ loading in female (E2-treated: 298 +/- 39 nmol/liter; untreated: 729 +/- 88 nmol/liter), but not in male (E2-treated: 1029 +/- 177 nmol/liter; untreated: 778 +/- 97 nmol/liter) cardiac cells. The protective action of E2 was not mimicked by the inactive estrogen stereoisomer, 10 nmol/liter 17alpha estradiol (17alpha estradiol-treated: 886 +/- 122 nmol/liter; untreated: 729 +/- 88 nmol/liter), and was abolished by tamoxifen (1 micromol/liter), which acts as an antagonist of E2 on estrogen receptors (E2 plus tamoxifen-treated: 702 +/- 98 nmol/liter; untreated: 729 +/- 88 nmol/liter). CONCLUSIONS: In a gender-dependent manner, E2 directly protects cardiac cells against hypoxia-reoxygenation injury through an estrogen receptor-mediated mechanism. Such property of E2 may contribute to cardioprotection in the female gender.

Animals↗
PubMed2000

Quadricepsplasty after war fractures.

Knee movements after fractures caused by explosive devices, as well as after intra-articular fractures of the knee, are often inadequate. This paper presents the results of quadriceps-plasty performed in 10 patients with the purpose of improving knee function. All of the patients were treated by the external fixation method, either after femoral fractures caused by explosive devices or for intra-articular knee fractures. All of them manifested markedly decreased knee flexion (15-70 degrees, with an average of 32 degrees). After quadricepsplasty and physical therapy, the achieved knee flexion was enough for normal walking (80-130 degrees, average 97.5 degrees). Mean knee mobility was increased 65.5 degrees. Our paper presents indications, methods, results, and complications for quadricepsplasty performed after war injuries.

Adult↗
PubMed1999

Pregnancy is not associated with altered morphology of the femoral artery.

While pregnancy is associated with adjustments in cardiovascular function, the morphology of the vascular system during pregnancy has been generally viewed as being very stable. However, recently we have demonstrated that pregnancy remodels the aorta and the carotid artery. In the present study, we assessed the morphological characteristics of the guinea-pig femoral artery during different stages of pregnancy using light and electron microscopy. There were no significant differences between external and internal diameters, wall thickness, total cross-sectional area and cross-sectional areas of lumen, intima, media, and adventitia of femoral arteries from non-pregnant and early-, mid- and late-pregnant guinea-pigs (n = 8-10). In previous studies, we have shown that the morphology of vascular smooth muscle and endothelial cells in the aorta and the carotid artery may be altered by pregnancy. Therefore, to test this possibility we measured diameters as well as cross-sectional areas of femoral arterial muscle and endothelial cells using electron microscopy. These parameters, at the electron microscopy level, were also not significantly changed by pregnancy (n = 8-10). It is concluded that the morphology of the guinea-pig femoral artery is not altered during pregnancy. In this regard, this study demonstrated that pregnancy-induced vascular remodelling varies between blood vessels that undergo the same functional alterations. Therefore, this may suggest that pregnancy-induced changes in blood flow through different vascular beds are not the most important factor involved in vascular remodelling observed during pregnancy. Rather, it is possible that haemodynamic-independent factors regulate pregnancy-mediated structural changes of the vascular wall.

Adaptation, Physiological↗
PubMed1999

Gene delivery of Kir6.2/SUR2A in conjunction with pinacidil handles intracellular Ca2+ homeostasis under metabolic stress.

Metabolic injury is a complex process affecting various tissues, with intracellular Ca2+ loading recognized as a common precipitating event leading to cell death. We have recently observed that cells overexpressing recombinant ATP-sensitive K+ (KATP) channel subunits may acquire resistance against metabolic stress. To examine whether, under metabolic challenge, intracellular Ca2+ homeostasis can be maintained by an activator of channel proteins, we delivered Kir6.2 and SUR2A genes, which encode KATP channel subunits, into a somatic cell line lacking native KATP channels. Hypoxia-reoxygenation was simulated by application and removal of the mitochondrial poison 2,4 dinitrophenol. Under such metabolic stress, Ca2+ loading was induced by Ca2+ influx during hypoxia and release of Ca2+ from intracellular stores during reoxygenation. Delivery of Kir6.2/SUR2A genes, in conjunction with the KATP channel activator pinacidil, prevented intracellular Ca2+ loading irrespective of whether the channel opener was applied throughout the duration of hypoxia-reoxygenation or transiently during the hypoxic or reoxygenation stage. In all stages of injury, the effect of pinacidil was inhibited by the selective antagonist of KATP channel, 5-hydroxydecanoate. The present study provides evidence that combined use of gene delivery and pharmacological targeting of recombinant proteins can handle intracellular Ca2+ homeostasis under hypoxia-reoxygenation irrespective of the stage of the metabolic insult.

Animals↗
PubMed1998

Recombinant cardiac ATP-sensitive K+ channel subunits confer resistance to chemical hypoxia-reoxygenation injury.

BACKGROUND: Opening of cardiac ATP-sensitive K+ (KATP) channels has emerged as a promising but still controversial cardioprotective mechanism. Defining KATP channel function at the level of recombinant channel proteins is a necessary step toward further evaluation of the cardioprotective significance of this ion conductance. METHODS AND RESULTS: KATP channel deficient COS-7 cells were found to be vulnerable to chemical hypoxia-reoxygenation injury that induced significant cytosolic Ca2+ loading (from 97+/-3 to 236+/-11 nmol/L). In these cells, the potassium channel opener pinacidil (10 micromol/L) did not prevent Ca2+ loading (from 96+/-3 nmol/L before to 233+/-12 nmol/L after reoxygenation) or evoked membrane current. Cotransfection with Kir6.2/SUR2A genes, which encode cardiac KATP channel subunits, resulted in a cellular phenotype that, in the presence of pinacidil (10 micromol/L), expressed K+ current and gained resistance to hypoxia-reoxygenation (Ca2+ concentration from 99+/-7 to 127+/-11 nmol/L; P>0.05). Both properties were abolished by the KATP channel blocker glyburide (1 micromol/L). In COS-7 cells transfected with individual channel subunits Kir6.2 or SUR2A, which alone do not form functional cardiac KATP channels, pinacidil did not protect against hypoxia-reoxygenation. CONCLUSIONS: The fact that transfer of cardiac KATP channel subunits protected natively KATP channel deficient cells provides direct evidence that the cardiac KATP channel protein complex harbors intrinsic cytoprotective properties. These findings validate the concept that targeting cardiac KATP channels should be considered a valuable approach to protect the myocardium against injury.

Adenosine Triphosphate↗
PubMed1998

Characterization of oxytocin actions in guinea-pig isolated uterine artery: the effect of pregnancy.

While the contractile effect of oxytocin on uterine artery has been reported, little is known about whether pregnancy affects the responsiveness of this artery to oxytocin. If it does, is it a consequence of changed endothelial function, as has been proposed for some other vasoconstrictors. Furthermore, the receptor subtypes involved in oxytocin action on uterine artery has not been yet determined. Therefore the purposes of this study were to (1) determine the receptor subtypes involved in oxytocin action in non-pregnant and pregnant guinea-pig uterine artery and to (2) determine whether possible changes in uterine artery sensitivity to oxytocin during pregnancy are due to altered endothelial function. Therefore, the effect of oxytocin on non-pregnant and pregnant guinea-pig uterine arterial rings with and without endothelium was investigated. In non-pregnant guinea-pig uterine artery oxytocin induced contraction (pEC50 = 7.63) with greater potency than in pregnant guinea-pig uterine artery (pEC50 = 7.17). Removal of the endothelium did not affect oxytocin-induced contractions, regardless of the pregnancy status. The uterine arteries did not respond to [Thr4, Gly7]oxytocin. In the preparations studied, [d(CH2)5Tyr(Me)2]vasopressin and [d(CH2)5, D-Ile2, Ile4]vasopressin antagonized oxytocin action with the following pKB values ([d(CH2)5Tyr(Me)2]vasopressin versus [d(CH2)5, D-Ile2, Ile4]vasopressin): 8.24 versus 7.29 and 8.11 versus 7.17 for non-pregnant guinea-pig uterine artery with and without endothelium, respectively; 8.39 versus 7.25 and 8.35 versus 7.25 for pregnant guinea-pig uterine artery with and without endothelium, respectively. We suggest that, in uterine arteries, oxytocin induces contraction by activation of vasopressin V1A receptors. The potency of oxytocin in uterine artery is decreased during pregnancy and this is not associated with altered endothelial function.

Animals↗
PubMed1998

Protective action of 17beta-estradiol in cardiac cells: implications for hyperkalemic cardioplegia.

BACKGROUND: Hyperkalemic cardioplegic solutions effectively arrest the heart, but may also induce intracellular Ca2+ loading and cellular hypercontracture, which could contribute to ventricular dysfunction associated with global surgical ischemia. Recently, it has been proposed that 17beta-estradiol may possess protective properties in the ischemic myocardium. The purpose of the present study was to examine the action of 17beta-estradiol on cardiac cells exposed to hyperkalemic stress. METHODS: Single ventricular cardiomyocytes, a preparation devoid of vascular and neuronal elements, were isolated from guinea pig hearts, loaded with a Ca2+-sensitive fluorescent probe, and imaged by digital epifluorescent microscopy. The emitted fluorescence of the probe, a measure of intracellular Ca2+ concentration, and cell length were simultaneously recorded during hyperkalemic challenge, in the absence or presence of 17beta-estradiol. RESULTS: In control cardiomyocytes, the cytosolic concentration of Ca2+ was 138+/-11 nmol/L and cell length 93+/-11 microm. Exposure to high K+ (+16 mmol/L KCl) significantly increased cytosolic Ca2+ to 2,191+/-87 nmol/L (p < 0.001), and produced cell shortening (length at 39+/-5 microm; p < 0.001). 17beta-Estradiol (10 micromol/L) acutely prevented high K+ to induce either intracellular Ca2+ loading (144+/-13 nmol/L, p < 0.001) or hypercontracture (91+/-10 microm, p < 0.001). Tamoxifen (10 micromol/L), an antiestrogen, abolished the protective effect of 17beta-estradiol. CONCLUSIONS: We conclude that 17beta-estradiol prevents hyperkalemia-induced Ca2+ loading and hypercontracture through a direct and tamoxifen-sensitive action in cardiomyocytes. This study raises the possibility that 17beta-estradiol should be considered as a cardioprotective adjunct toward a safer hyperkalemic cardioplegia.

Animals↗
PubMed1998

Pregnancy is associated with hypotrophy of carotid artery endothelial and smooth muscle cells.

It is known that blood flow through the carotid artery is decreased during pregnancy, which may be due to a pregnancy-associated increase in the sensitivity of this artery to vasoconstrictors. Recent studies have shown that alteration of blood flow or pressure could remodel some arteries over a short time frame. However, the possibility of remodelling of the carotid artery during pregnancy has not yet been examined. Therefore, the aim of the present study was to study the morphometrical and stereological characteristics of guinea-pig carotid artery during different stages of pregnancy (non-pregnant, early-pregnant, mid-pregnant, late-pregnant, n = 8-10 for each group). The cross-sectional area of the different layers of the carotid artery and the cross-sectional area of endothelial and smooth muscle cells were measured using both light and electron microscopy. The values of internal diameter and cross-sectional area of adventitia were not significantly different, regardless of the pregnancy status. In contrast, external diameter, wall thickness and cross-sectional areas of media and intima progressively and significantly decreased during pregnancy. In addition, volume/surface density ratio of intima and media also significantly and progressively decreased during pregnancy, suggesting hypotrophy of endothelial and smooth muscle cells of carotid artery. Indeed, electron microscopy revealed that the size, defined as cross-sectional area, of endothelial and smooth muscle cells was significantly decreased during different stages of pregnancy. It is concluded that during pregnancy there is thinning of the intimal and medial layers of guinea-pig carotid artery, which reflect pregnancy-associated hypotrophy of carotid artery endothelial and smooth muscle cells.

Animals↗
PubMed1998

Predominant role for nitric oxide in the relaxation induced by vasoactive intestinal polypeptide in human uterine artery.

It has been previously shown that vasoactive intestinal polypeptide (VIP) induces endothelium-dependent relaxation of the human uterine artery. However, the nature of the mediator of the VIP-induced endothelium-dependent relaxation of the human uterine artery has not yet been determined. Therefore these experiments were undertaken to examine the effects of VIP on human uterine arteries and to establish the role of various endothelial factors on the relaxation induced by VIP. The experiments were performed on isolated human uterine arterial rings. VIP (0.3-100 nM) induced a concentration-dependent relaxation of human uterine arteries with intact endothelium (pEC50 = 8.06+/-0.14, n = 28). After the removal of the endothelium this relaxation was abolished (n = 6). Indomethacin (10 microM), a cyclooxygenase inhibitor, and diethylcarbamazine (100 microM), a lipoxygenase blocker, had no effects on VIP-induced relaxation. In contrast, methylene blue (10 microM), a blocker of guanylate cyclase, NG-monomethyl-L-arginine (10 microM), an inhibitor of nitric oxide (NO) synthase, and 4-aminopyridine (1 mM), a non-selective blocker of K+ channels, antagonized the effect of VIP with suppression of maximal VIP-induced relaxation. Non-competitive antagonism with methylene blue revealed that the pKa value for VIP-receptor complex was 8.10+/-0.10 (n = 6) and the receptor reserve expressed as KA/EC50 was 0.89+/-0.11, where pKa = log10KA, and KA is the dissociation constant of VIP-receptor complex. Therefore, on the basis of the results presented, we can conclude that VIP induces endothelium-dependent relaxation in human uterine arteries, acting as a partial agonist on this blood vessel. It appears that endothelium-dependent relaxation induced by VIP in human uterine artery can be entirely explained by the release of NO from endothelial cells.

4-Aminopyridine↗
PubMed1998

Mitochondrial ATP-sensitive K+ channels modulate cardiac mitochondrial function.

Discovered in the cardiac sarcolemma, ATP-sensitive K+ (KATP) channels have more recently also been identified within the inner mitochondrial membrane. Yet the consequences of mitochondrial KATP channel activation on mitochondrial function remain partially documented. Therefore, we isolated mitochondria from rat hearts and used K+ channel openers to examine the effect of mitochondrial KATP channel opening on mitochondrial membrane potential, respiration, ATP generation, Ca2+ transport, and matrix volume. From a mitochondrial membrane potential of -180 +/- 15 mV, K+ channel openers, pinacidil (100 microM), cromakalim (25 microM), and levcromakalim (20 microM), induced membrane depolarization by 10 +/- 7, 25 +/- 9, and 24 +/- 10 mV, respectively. This effect was abolished by removal of extramitochondrial K+ or application of a KATP channel blocker. K+ channel opener-induced membrane depolarization was associated with an increase in the rate of mitochondrial respiration and a decrease in the rate of mitochondrial ATP synthesis. Furthermore, treatment with a K+ channel opener released Ca2+ from mitochondria preloaded with Ca2+, an effect also dependent on extramitochondrial K+ concentration and sensitive to KATP channel blockade. In addition, K+ channel openers, cromakalim and pinacidil, increased matrix volume and released mitochondrial proteins, cytochrome c and adenylate kinase. Thus, in isolated cardiac mitochondria, KATP channel openers depolarized the membrane, accelerated respiration, slowed ATP production, released accumulated Ca2+, produced swelling, and stimulated efflux of intermembrane proteins. These observations provide direct evidence for a role of mitochondrial KATP channels in regulating functions vital for the cardiac mitochondria.

Adenosine Triphosphate↗
PubMed1998

Infection with Helicobacter pylori and long-term use of non-steroidal antiinflammatory drugs.

The use of nonsteroidal anti inflammatory drugs (NSAID) is associated with an increased risk of peptic ulcer and of ulcer complications. However, the relation between Helicobacter pylori infection and gastroduodenal damage associated with NSAID use is unclear. This study investigated the prevalence of Helicobacter pylori infection in patients with arthritis (n = 85) taking NSAID, trying to find out whether the patients taking NSAID and infected with H. pylori were more likely to have dyspepsia, mucosal damage or chronic active gastritis than those without H. pylori infection. H. pylori was identified by biopsy, rapid urease test and histologic test. Dispeptic symptoms were assessed according to a standardized questionnaire. Gastroduodenal mucosal damage was graded endoscopically (using a modified Lanza scale) and the diagnosis of chronic gastritis was based on the histologic criteria of the Sydney system. The frequency of H. pylori infection was found to increase with age. No statistically significant difference was observed in the presence of damage to gastroduodenal mucosa between the patients with and without H. pylori infection. H. pylori infection was found to be associated with an increased frequency and severity of dyspeptic symptoms in patients with arthritis taking long-term NSAID. Chronic active gastritis was only present in patients with H. pylori infection. H. pylori infection was shown to be associated with an increased frequency and severity of dyspeptic symptoms in patients with arthritis on long-term NSAID therapy, without causing an increased damage to gastroduodenal mucosa.

Adult↗
PubMed1997

Effect of oxytocin as a partial agonist at vasoconstrictor vasopressin receptors on the human isolated uterine artery.

1. The effect of oxytocin on endothelium-intact and endothelium-denuded segments of the human uterine artery rings was investigated. 2. In both types of preparation oxytocin induced contraction of human uterine artery with similar potency and efficacy (pEC50 values: 6.95 +/- 0.05 vs 7.06 +/- 0.01; maximal response values: 61 +/- 4.1% vs 63 +/- 5.1% for arteries with and without endothelium, respectively). 3. In contrast, human uterine arteries, both intact and denuded of endothelium, did not respond to the addition of the selective oxytocin receptor agonist, [Thr4, Gly7]oxytocin (10 nM(-1) microM). 4. The vasopressin receptor antagonists, [d(CH2)5Tyr(Me)]AVP (10-100nM) and [d(CH2)5,D-Ile2,Ile4]AVP (300 nM-3 microM) produced parallel rightward shifts of the curves for oxytocin. The Schild plots constrained to a slope of unity gave the following -log K(B) values: [d(CH2)5Tyr(Me)] AVP vs [d(CH2)5,D-Ile2,Ile4] AVP 9.24 vs 6.91 and 9.26 vs 6.84 for human uterine artery with intact and those denuded of endothelium, respectively. In contrast, in both types of preparations the oxytocin receptor antagonist, [d(CH2)5Tyr(OMe), 2Orn8]vasotocin (1 microM), did not significantly affect oxytocin-induced contractions. 5. The calculated pK(A) values for oxytocin itself also did not differ between preparations: 6.56 and 6.43 for human uterine artery with and without endothelium, respectively. In both types of preparations, the receptor reserve (K(A)/EC50) was close to unity (intact vs denuded: 3.9 vs 3.0). 6. It is concluded that, in human uterine artery, oxytocin induces contractions that are not modulated by the endothelium. It is likely that oxytocin acts as a partial agonist on human uterine artery, regardless of the endothelial condition. On the basis of differential antagonists affinity and affinity of oxytocin itself, it is probable that receptors involved in oxytocin-induced contraction in human uterine arteries belong to the V(1A) vasopressin receptors.

Adult↗
PubMed1997

Remodelling of guinea-pig aorta during pregnancy: selective alteration of endothelial cells.

It is known that aortic blood flow is increased during pregnancy, which may be due to a pregnancy-associated decrease in aorta sensitivity to vasoconstrictors on one side, and increased response to vasodilators on the other. Recent studies have shown that alteration of blood flow or pressure could remodel some arteries over a short time frame. However, the possibility of remodelling of aorta during pregnancy has not yet been examined. Therefore, the aim of the present study was to assess the morphometric and stereological characteristics of guinea-pig aorta during different stages of pregnancy (non-pregnant, early-pregnant, mid-pregnant, late-pregnant, n = 8-10 for each group). The cross-sectional areas of different aortic layers and of endothelial cells were measured using both light and electron microscopy. The values of external and internal diameters, wall thickness, total cross-sectional area and cross-sectional area of media and adventitia were not significantly different, regardless of the stage of pregnancy. In contrast, the cross-sectional area of intima significantly and progressively decreased during pregnancy (non-pregnant: 61 +/- 5 x 10(4) microm2, late-pregnant: 38 +/- 3 microm2, P < 0.01). The volume:surface density ratio of intima also significantly and progressively decreased during pregnancy (non-pregnant: 5.31 +/- 0.51, late-pregnant: 4.38 +/- 0.42, P < 0.01). Electron microscopy revealed that the cross-sectional area of endothelial cells was significantly decreased during different stages of pregnancy (non-pregnant: 56.8 +/- 6.2 microm2, late-pregnant: 28.9 +/- 3.8 microm2, P < 0.01). It is concluded that during pregnancy there is selective thinning of intimal layer of guinea-pig aorta, which probably reflects hypotrophy of aortic endothelial cells.

Animals↗
PubMed1997

Endothelium-dependent relaxation in response to acetylcholine in pregnant guinea-pig uterine artery.

Recently, strong evidence has suggested that nitric oxide (NO) synthesis is significantly increased in the uterine artery during pregnancy, which may mediate the increased blood flow to the uterus that is characteristic of pregnancy. We therefore investigated the nature of the mediators of acetylcholine (ACh)-induced relaxation in pregnant guinea-pig uterine arterial rings. ACh (0.1 nM to 60 microM) induced endothelium-dependent relaxation of phenylephrine-precontracted pregnant guinea-pig uterine artery. N(G)-monomethyl-L-arginine (3-30 microM) antagonized the effect of ACh, with suppression of maximal ACh-induced relaxation, in a concentration-dependent manner. The inhibition of relaxation by N(G)-monomethyl-L-arginine (10 microM) was significantly overcome by L-arginine (10 microM), but not by D-arginine (100 microM). On the contrary, the administration of indomethacin (10 microM) and diethylcarbamazine (100 microM) did not modify the relaxation of guinea-pig uterine artery induced by ACh. The ACh-evoked relaxation was unaltered when K+-rich Krebs-Ringer bicarbonate solution was used to induce tone instead of phenylephrine, or when a nonselective blocker of K+ channels, 4-aminopyridine (6 mM), was applied to phenylephrine-precontracted segments. It is concluded that the relaxation induced by ACh in pregnant guinea-pig uterine artery can be explained entirely by the release of NO from vascular endothelial cells, without involvement of other endothelium-derived relaxing factors, similar to that previously reported for non-pregnant guinea-pig uterine artery. Thus, it seems that increased activity of NO synthase during pregnancy is without significant influence on the ACh action on uterine artery.

Acetylcholine↗