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1.
J Hypertens ; 38(4): 679-691, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31834119

RESUMO

BACKGROUND/AIMS: The current study investigated the long-term effects of prenatal caffeine (Caf) exposure on cerebral vessels of old offspring rats. METHODS: Pregnant rats were treated with Caf (20 mg/kg, twice daily) or 0.9% normal saline during gestational days 3.5-19.5, and offspring were tested at 24 months old. Vascular functions of middle cerebral arteries and ion channel activities in smooth muscle cells were examined using myograph system and patch-clamp. RESULTS: Prenatal Caf exposure decreased isoprenaline (ß-adrenergic agonist)-induced dilatation of the middle cerebral artery in the offspring. Treatment with protein kinase A (PKA) inhibitor reduced isoprenaline-mediated vasodilatation to a greater extent in the control. Forskolin-mediated vasodilatation and membrane hyperpolarization were reduced in the Caf group. Large-conductance Ca-activated K (BKCa) channel inhibitor iberiotoxin significantly attenuated forskolin-induced vasodilatation and reduced depolarization in the control, not in the Caf group. The PKA agonist-activated cell-attached single BKCa currents to a greater extent in the control. The mRNA and protein expression levels of PKA-Cα were decreased. The sensitivity of ryanodine receptors to the PKA agonist was blunted in the Caf group, whereas the mRNA expression of ryanodine receptor 2 subunit was reduced. Voltage/Ca sensitivity of BKCa was decreased accompanied by reduced mRNA and protein expression of BKCa-ß1 subunits in the Caf group. PKA agonist-stimulated inside-out BKCa currents were weaker in the Caf group. CONCLUSION: Prenatal exposure to Caf-affected isoprenaline/forskolin-mediated vascular functions in aged cerebral arteries, related to dysfunction of the PKA/ryanodine receptors/BKCa signaling pathway.


Assuntos
Cafeína/farmacologia , Artérias Cerebrais/efeitos dos fármacos , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Regulação para Baixo/efeitos dos fármacos , Canais de Potássio Ativados por Cálcio de Condutância Alta/metabolismo , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Cálcio/metabolismo , Artérias Cerebrais/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/genética , Feminino , Canais de Potássio Ativados por Cálcio de Condutância Alta/genética , Masculino , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Gravidez , Ratos , Ratos Sprague-Dawley , Canal de Liberação de Cálcio do Receptor de Rianodina/genética
2.
J Cell Mol Med ; 23(2): 1183-1196, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30556291

RESUMO

BACKGROUND: This study aimed to examine whether and how postnatal high-fat diet had additional impact on promoting vascular dysfunction in the offspring exposed to prenatal hypoxia. METHODS AND RESULTS: Pregnant Sprague-Dawley rats were randomly assigned to hypoxia (10.5% oxygen) or normoxia (21% O2 ) groups from gestation days 5-21. A subset of male offspring was placed on a high-fat diet (HF, 45% fat) from 4-16 weeks of age. Prenatal hypoxia induced a decrease in birth weight. In offspring-fed HF diet, prenatal hypoxia was associated with increased fasting plasma triglyceride, total cholesterol, free fatty acids, and low-density lipoprotein-cholesterol. Compared with the other three groups, prenatal hypoxic offspring with high-fat diet showed a significant increase in blood pressure, phenylephrine-mediated vasoconstrictions, L-type voltage-gated Ca2+ (Cav1.2) channel currents, and elevated mRNA and protein expression of Cav1.2 α1 subunit in mesenteric arteries or myocytes. The large-conductance Ca2+-activated K+ (BK) channels currents and the BK channel units (ß1, not α-subunits) were significantly increased in mesenteric arteries or myocytes in HF offspring independent of prenatal hypoxia factor. CONCLUSION: The results demonstrated that prenatal hypoxia followed by postnatal HF caused vascular dysfunction through ion channel remodelling in myocytes.


Assuntos
Canais de Cálcio Tipo L/metabolismo , Dieta Hiperlipídica/efeitos adversos , Hipóxia/fisiopatologia , Artérias Mesentéricas/patologia , Efeitos Tardios da Exposição Pré-Natal/etiologia , Doenças Vasculares/etiologia , Animais , Animais Recém-Nascidos , Pressão Sanguínea , Sinalização do Cálcio , Feminino , Ativação do Canal Iônico , Masculino , Artérias Mesentéricas/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Efeitos Tardios da Exposição Pré-Natal/patologia , Ratos , Ratos Sprague-Dawley , Doenças Vasculares/metabolismo , Doenças Vasculares/patologia , Vasoconstrição , Vasodilatação
3.
Physiol Res ; 67(6): 975-983, 2018 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-30204465

RESUMO

Prenatal exposure to caffeine can cause developmental problems. This study determined chronic influence of prenatal caffeine at relatively higher doses on cognitive functions in the rat offspring. Pregnant Sprague-Dawley rats (4-month-old) were exposed to caffeine (20 mg/kg, twice a day) for whole pregnancy from gestational day 4. Fetal and offspring body and brain weight was measured. Learning and memory were tested in adult offspring with Morris water maze. Learning and memory-related receptors were measured. The exposure to prenatal caffeine not only caused fetal growth restriction, but also showed long-term effects on learning and memory in the offspring. The caffeine offspring exhibited longer escape latency and path length in navigation testing. The number of passing the target was significantly reduced in those offspring. The expression of adenosine A(1) and A(2A) receptors, nuclear PKA C(alpha), C(beta) subunits, and pCREB were significantly increased in the fetal and neonatal brain, and suppressed in the hippocampus of the adult offspring. The expression of BDNF and TrkB were reduced regardless of various ages. The results suggest that intrauterine programming dysfunction of adenosine receptors and the down-stream of cAMP/PKA/pCREB system may play an important role in prenatal caffeine induced cognition disorders in the adult offspring.


Assuntos
Cafeína/toxicidade , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/metabolismo , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Feminino , Masculino , Aprendizagem em Labirinto/fisiologia , Memória/efeitos dos fármacos , Memória/fisiologia , Transtornos da Memória/diagnóstico , Gravidez , Efeitos Tardios da Exposição Pré-Natal/diagnóstico , Ratos , Ratos Sprague-Dawley , Receptores Purinérgicos P1/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia
4.
J Am Heart Assoc ; 7(6)2018 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-29545262

RESUMO

BACKGROUND: Prenatal hypoxia is suggested to be associated with increased risks of hypertension in offspring. This study tested whether prenatal hypoxia resulted in salt-sensitive offspring and its related mechanisms of vascular ion channel remodeling. METHODS AND RESULTS: Pregnant rats were housed in a normoxic (21% O2) or hypoxic (10.5% O2) chamber from gestation days 5 to 21. A subset of male offspring received a high-salt diet (8% NaCl) from 4 to 12 weeks after birth. Blood pressure was significantly increased only in the salt-loading offspring exposed to prenatal hypoxia, not in the offspring that received regular diets and in control offspring provided with high-salt diets. In mesenteric artery myocytes from the salt-loading offspring with prenatal hypoxia, depolarized resting membrane potential was associated with decreased density of L-type voltage-gated Ca2+ (Cav1.2) and voltage-gated K+ channel currents and decreased calcium sensitive to the large-conductance Ca2+-activated K+ channels. Protein expression of the L-type voltage-gated Ca2+ α1C subunit, large-conductance calcium-activated K+ channel (ß1, not α subunits), and voltage-gated K+ channel (KV2.1, not KV1.5 subunits) was also decreased in the arteries of salt-loading offspring with prenatal hypoxia. CONCLUSIONS: The results demonstrated that chronic prenatal hypoxia may program salt-sensitive hypertension in male offspring, providing new information of ion channel remodeling in hypertensive myocytes. This information paves the way for early prevention and treatments of salt-induced hypertension related to developmental problems in fetal origins.


Assuntos
Pressão Sanguínea , Canais de Cálcio Tipo L/metabolismo , Hipertensão/etiologia , Hipóxia/complicações , Subunidades beta do Canal de Potássio Ativado por Cálcio de Condutância Alta/metabolismo , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Efeitos Tardios da Exposição Pré-Natal , Canais de Potássio Shab/metabolismo , Cloreto de Sódio na Dieta , Animais , Sinalização do Cálcio , Regulação para Baixo , Feminino , Idade Gestacional , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Hipóxia/metabolismo , Hipóxia/fisiopatologia , Masculino , Potenciais da Membrana , Artérias Mesentéricas/metabolismo , Artérias Mesentéricas/fisiopatologia , Músculo Liso Vascular/fisiopatologia , Gravidez , Ratos Sprague-Dawley , Fatores de Risco
5.
Cell Physiol Biochem ; 45(4): 1603-1616, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29486465

RESUMO

BACKGROUND/AIMS: Chronic hypoxia in utero could impair vascular functions in the offspring, underlying mechanisms are unclear. This study investigated functional alteration in large-conductance Ca2+-activated K+ (BK) channels in offspring mesenteric arteries following prenatal hypoxia. METHODS: Pregnant rats were exposed to normoxic control (21% O2, Con) or hypoxic (10.5% O2, Hy) conditions from gestational day 5 to 21, their 7-month-old adult male offspring were tested for blood pressure, vascular BK channel functions and expression using patch clamp and wire myograh technique, western blotting, and qRT-PCR. RESULTS: Prenatal hypoxia increased pressor responses and vasoconstrictions to phenylephrine in the offspring. Whole-cell currents density of BK channels and amplitude of spontaneous transient outward currents (STOCs), not the frequency, were significantly reduced in Hy vascular myocytes. The sensitivity of BK channels to voltage, Ca2+, and tamoxifen were reduced in Hy myocytes, whereas the number of channels per patch and the single-channel conductance were unchanged. Prenatal hypoxia impaired NS1102- and tamoxifen-mediated relaxation in mesenteric arteries precontracted with phenylephrine in the presence of Nω-nitro-L-arginine methyl ester. The mRNA and protein expression of BK channel ß1, not the α-subunit, was decreased in Hy mesenteric arteries. CONCLUSIONS: Impaired BK channel ß1-subunits in vascular smooth muscle cells contributed to vascular dysfunction in the offspring exposed to prenatal hypoxia.


Assuntos
Hipóxia Fetal , Canais de Potássio Ativados por Cálcio de Condutância Alta/metabolismo , Artérias Mesentéricas/metabolismo , Animais , Pressão Sanguínea/efeitos dos fármacos , Regulação para Baixo , Feminino , Idade Gestacional , Canais de Potássio Ativados por Cálcio de Condutância Alta/genética , Masculino , Potenciais da Membrana/efeitos dos fármacos , Artérias Mesentéricas/citologia , Artérias Mesentéricas/efeitos dos fármacos , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/fisiologia , Técnicas de Patch-Clamp , Peptídeos/farmacologia , Fenilefrina/farmacologia , Gravidez , Subunidades Proteicas/genética , Subunidades Proteicas/metabolismo , Ratos , Ratos Sprague-Dawley , Tamoxifeno/farmacologia , Tetrazóis/farmacologia , Tioureia/análogos & derivados , Tioureia/farmacologia , Vasoconstrição/efeitos dos fármacos
6.
Mol Nutr Food Res ; 62(5)2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29346712

RESUMO

SCOPE: High sucrose intake during pregnancy is linked to type 2 diabetes mellitus and altered insulin resistance. METHODS AND RESULTS: This study attempts to ascertain whether prenatal high sucrose intake (20% sucrose) alleviates the detrimental effects of high postnatal sugar consumption in the offspring, and the molecular mechanisms are investigated using a rat model. High prenatal sucrose exposure increases the body weight of the offspring at 1-3 weeks of age. Exposure to both prenatal and postnatal high sucrose increases glucose tolerance in the 4-month-old adult offspring compared with offspring receiving other treatments. Postnatal high sucrose exposure suppresses food intake but increases the total daily caloric and fluid intake. Both fasting blood glucose and plasma triglyceride levels are increased, but the fasting insulin level is unaffected. Prenatal high sucrose intake enlarges pancreatic islet area; however, prenatal-plus-postnatal high sucrose exposure induces smaller pancreatic islets. IRS-1(S612) protein phosphorylation is significantly increased, and the GSK-3ß (S9) phosphorylation level is reduced. CONCLUSION: Both prenatal and prenatal-plus-postnatal high sucrose exposure substantially affect biological functions related to insulin homeostasis. IRS-1(S612) protein phosphorylation appears to be a part of the molecular mechanism underlying these effects. These results add to the understanding of how high sucrose intake contributes to insulin resistance and diabetes pathogenesis and how postnatal nutrition and lifestyle may mitigate detrimental prenatal exposures.


Assuntos
Glicemia/análise , Resistência à Insulina , Efeitos Tardios da Exposição Pré-Natal , Sacarose/efeitos adversos , Animais , Peso Corporal , Jejum/sangue , Feminino , Teste de Tolerância a Glucose , Proteínas Substratos do Receptor de Insulina/metabolismo , Gravidez , Ratos , Ratos Sprague-Dawley , Sacarose/administração & dosagem
7.
Biosci Rep ; 37(3)2017 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-28515221

RESUMO

Prenatal insults have been shown to affect vascular functions, leading to increased risks of cardiovascular diseases in offspring. The present study determined whether high sucrose (HS) intake in pregnancy affected central vascular functions in middle cerebral artery (MCA) of offspring. Sprague-Dawley rats were fed a standard food and tap water with normal or high (20%) sucrose content during pregnancy. Offspring were maintained with normal diets and tap water. Central vascular functions and related ion channels were assessed in male offspring at 5 months old. Compared with the control, angiotensin II (AII)-induced vasoconstrictions were significantly higher in the MCA of the offspring exposed to prenatal HS. In the MCA, large conductance Ca2+-activated K+ channels (BKCa) currents were decreased with a reduction of opening frequency, sensitivity to intracellular Ca2+/membrane voltage, and BKß1 expression. mRNA levels of AT1α and AT2, as well as AT1/AT2 ratio, were significantly increased in the MCA of offspring following exposure to prenatal HS diets. The data suggested that prenatal HS diets could alter microvascular activities in the MCA, probably via changes of BKCa channels in the brain.


Assuntos
Angiotensina II/metabolismo , Encéfalo/irrigação sanguínea , Dieta/efeitos adversos , Sacarose Alimentar/efeitos adversos , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/metabolismo , Microvasos/metabolismo , Artéria Cerebral Média/metabolismo , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Doenças Vasculares/metabolismo , Análise de Variância , Angiotensina II/genética , Animais , Cálcio/metabolismo , Feminino , Glucose/análise , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/análise , Masculino , Microvasos/química , Artéria Cerebral Média/química , Técnicas de Patch-Clamp , Potássio/metabolismo , Gravidez , Ratos , Ratos Sprague-Dawley , Receptores de Angiotensina/genética , Receptores de Angiotensina/metabolismo , Vasoconstrição
8.
Oncotarget ; 8(19): 30734-30741, 2017 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-28430615

RESUMO

The present study tested the hypothesis that angiotensin II plays a role in the regulation of placental vascular tone, which contributes to hypertension in preeclampsia. Functional and molecular assays were performed in large and micro placental and non-placental vessels from humans and animals. In human placental vessels, angiotensin II induced vasoconstrictions in 78.7% vessels in 155 tests, as referenced to KCl-induced contractions. In contrast, phenylephrine only produced contractions in 3.0% of 133 tests. In non-placental vessels, phenylephrine induced contractions in 76.0% of 67 tests, whereas angiotensin II failed to produce contractions in 75 tests. Similar results were obtained in animal placental and non-placental vessels. Compared with non-placental vessels, angiotensin II receptors and ß-adrenoceptors were significantly increased in placental vessels. Compared to the vessels from normal pregnancy, angiotensin II-induced vasoconstrictions were significantly reduced in preeclamptic placentas, which was associated with a decrease in angiotensin II receptors. In addition, angiotensin II and angiotensin converting enzyme in the maternal-placenta circulation in preeclampsia were increased, whereas angiotensin I and angiotensin1-7 concentrations were unchanged. The study demonstrates a selective effect of angiotensin II in maintaining placental vessel tension, which may play an important role in development of hypertension in preeclampsia.


Assuntos
Angiotensina II/metabolismo , Hemodinâmica , Placenta/metabolismo , Placenta/fisiopatologia , Circulação Placentária , Pré-Eclâmpsia/metabolismo , Pré-Eclâmpsia/fisiopatologia , Animais , Catecolaminas/metabolismo , Feminino , Humanos , Hipertensão/etiologia , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Pré-Eclâmpsia/genética , Gravidez , Receptores Adrenérgicos/genética , Receptores Adrenérgicos/metabolismo , Sistema Renina-Angiotensina , Ovinos , Vasoconstrição/efeitos dos fármacos
9.
Biol Reprod ; 96(5): 1085-1095, 2017 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-28430866

RESUMO

Overnutrition during pregnancy could increase risks of cardiovascular diseases in late life. This study investigated whether and how reactive oxygen species (ROS) may influence functions of large-conductance Ca2+-activated K+ channels (BKCa) in the offspring exposed to prenatal high sucrose (HS). We found that prenatal HS diets significantly increased phenylephrine (PE)-induced vessel contractions in mesenteric arteries of the adult offspring. Pretreatment with iberiotoxin (BKCa blocker, IBTX) significantly increased PE-mediated vascular contractions in the control, not in the HS group. Electrophysiological studies demonstrated that BKCa current density and single-channel current were reduced in the vascular smooth muscle cells (VSMCs) of the HS offspring. The expression of BKCa alpha, beta1 subunits in mesenteric arteries was decreased in the HS offspring, indicating that both activity and number of BKCa channels in HS offspring were reduced. Superoxide production and NADPH oxidase (NOX)4 of the HS offspring were elevated. Following inhibiting NOX by apocynin, vasoconstriction in the HS offspring was weakened and the reduced currents in the VSMCs were improved with altered protein kinase B (AKT) pathway. The results suggested that NOX4-derived ROS might inhibit the offspring vascular BKCa channel activity via AKT pathway.


Assuntos
Sacarose Alimentar/efeitos adversos , Canais de Potássio Ativados por Cálcio de Condutância Alta/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Animais , Glicemia/metabolismo , Dieta , Feminino , Canais de Potássio Ativados por Cálcio de Condutância Alta/biossíntese , Masculino , Artérias Mesentéricas/metabolismo , Músculo Liso Vascular/efeitos dos fármacos , NADPH Oxidase 4/metabolismo , Proteína Oncogênica v-akt/metabolismo , Peptídeos/farmacologia , Fenilefrina/farmacologia , Bloqueadores dos Canais de Potássio/farmacologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Ratos , Ratos Sprague-Dawley , Vasoconstritores/farmacologia
10.
Mol Nutr Food Res ; 61(8)2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28133948

RESUMO

SCOPE: High salt (HS) diets are related to cardiovascular diseases, and prenatal HS was suggested to increase risks of coronary artery diseases in the offspring. This study tested the hypothesis that prenatal HS may influence Adenosine-induced vasodilatation via protein kinase A (PKA) pathway in coronary arteries. METHODS AND RESULTS: Sprague-Dawley rats were fed with 8% salt diet for gestation, the control was fed with 0.3% salt diet. Coronary arteries from male adult offspring were tested for K+ channels and Adenosine signal pathways. Adenosine-mediated vasodilatation was reduced in coronary arteries in HS. There was no difference in gene expression of A2A receptors between the two groups. After pretreatment with PKA inhibitor, vasodilatation to Adenosine was decreased to a smaller extent in HS than that in control. Forskolin (activator of adenylate cyclase)-mediated vasodilatation was decreased in HS. Iberiotoxin (large-conductance Ca2+ -activated K+ channel [BK channel] inhibitor) attenuated Forskolin-induced vasodilatation in control, not in HS group. Currents of BK channels decreased in coronary artery smooth muscle cells, and PKA-modulated BK channel functions were declined. Protein levels of BK ß1 and PKA C-subunits in coronary arteries of HS offspring were reduced. CONCLUSIONS: Prenatal HS diets altered Adenosine-mediated coronary artery vasodilatation in the offspring, which was linked to downregulation of cAMP/PKA/BK channel pathway.


Assuntos
Adenosina/metabolismo , Vasos Coronários/efeitos dos fármacos , Cloreto de Sódio na Dieta/farmacologia , Vasodilatação/efeitos dos fármacos , Adenosina/farmacologia , Animais , Animais Recém-Nascidos , Vasos Coronários/metabolismo , AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Feminino , Canais de Potássio Ativados por Cálcio de Condutância Alta/metabolismo , Masculino , Fenômenos Fisiológicos da Nutrição Materna , Músculo Liso Vascular/citologia , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Ratos Sprague-Dawley , Receptor A2A de Adenosina/metabolismo , Transdução de Sinais
11.
Curr Top Med Chem ; 17(15): 1692-1708, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27848900

RESUMO

Rhodiola as one of traditional medicines has been used for clinical treatments due to its strong antioxidant properties. Phytochemical analysis revealed the presence of flavonoids, phenylpropanoids, phenylethanol/benzyl alcohol derivatives, cyanogenic glycosides and terpenoids. The bioactive compounds had been demonstrated to be effective at scavenging reactive oxygen species (ROS). The structures contain phenolic hydroxyl groups and unsaturated bonds. This article reviews antioxidant capacities of the extracts and bioactive components derived from Rhodiola plants. As the major pharmacological ingredient, salidroside is rigorously investigated and used in scientific researches and clinical practices. Accumulated evidences indicated that extracts of Rhodiola plants or salidroside could be able to reverse DNA damage and alter expression of cytokines and antioxidative enzymes induced by ROS. The underlying mechanisms for the antioxidative effects of the herb have been investigated in the last two decades. We summarize the possible effects and acting pathways for the herb involved in several chronic diseases in cardiovascular, respiratory, and nervous systems, as well as potential epigenetic influences. The information generated from experimental and clinical studies offered valuable insights for further investigations of medical potentials of Rhodiola plants.


Assuntos
Antioxidantes/farmacologia , Doenças Cardiovasculares/tratamento farmacológico , Doenças do Sistema Nervoso/tratamento farmacológico , Compostos Fitoquímicos/farmacologia , Transtornos Respiratórios/tratamento farmacológico , Rhodiola/química , Antioxidantes/química , Antioxidantes/isolamento & purificação , Humanos , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Fitoterapia , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia
12.
Reprod Toxicol ; 65: 95-103, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27421582

RESUMO

We recently demonstrated that acetylcholine (ACh) produced reliable vasoconstrictions in the umbilical cords. This study investigated the possible mechanisms with different antagonists. ACh-mediated vasoconstrictions were decreased by voltage-operated calcium (Ca2+) channels antagonist nifedipine or inositol-1,4,5-trisphosphate-mediated Ca2+ release antagonist 2-aminoethyl diphenylborinate, indicating that both extracellular and intracellular calcium modulated the ACh-stimulated umbilical contraction. Intracellular Ca2+ concentrations were increased simultaneously with vasoconstrictions by ACh in the umbilical vessels. Inhibiting large-conductance calcium-dependent potassium (BK) channels enhanced ACh-mediated contraction, whereas inhibiting voltage dependent potassium (K+), inward rectifier K+ and ATP-sensitive K+ channels had no effects. Incubation with specific K+ channel inhibitors showed that ACh suppressed BK currents rather than 4-aminopyridine-sensitive K+ channels currents. The results suggested that blood vessels in umbilical cords had special characteristics in response to cholinergic signals. ACh-stimulated umbilical vasoconstrictions were mediated via muscarinic receptor subtype 1/3-protein kinase C/cyclooxygenase-BK channel pathways.


Assuntos
Acetilcolina/farmacologia , Canais de Cálcio/fisiologia , Agonistas Colinérgicos/farmacologia , Canais de Potássio/fisiologia , Cordão Umbilical/efeitos dos fármacos , Vasoconstrição/efeitos dos fármacos , Animais , Cálcio/fisiologia , Bloqueadores dos Canais de Cálcio/farmacologia , Artérias Carótidas/efeitos dos fármacos , Artérias Carótidas/fisiologia , Feminino , Técnicas In Vitro , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/fisiologia , Bloqueadores dos Canais de Potássio/farmacologia , Gravidez , Coelhos , Ratos Sprague-Dawley , Cordão Umbilical/fisiologia
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