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1.
Einstein (Sao Paulo) ; 17(3): eAO4600, 2019 Jun 03.
Article in English, Portuguese | MEDLINE | ID: mdl-31166411

ABSTRACT

OBJECTIVE: To characterize the calcium influx pathways implicated in the sustained elevation of endothelial intracellular calcium concentration, required for the synthesis and release of relaxing factors. METHODS: We evaluated the effect of the newly synthesized pyrazole derivatives, described as selective inhibitors for ORAI (BTP2/Pyr2 and Pyr6) and TRPC3 (Pyr3 and Pyr10) channels, upon endothelium- and extracellular calcium-dependent relaxations stimulated by acetylcholine and thapsigargin, in pre-constricted rat thoracic aortic rings. RESULTS: Acetylcholine and thapsigargin responses were completely reverted by Pyr2 and Pyr6 (1 to 3µM). Pyr3 (0.3 to 3µM) caused a rapid reversal of acetylcholine (6.2±0.08mg.s-1) and thapsigargin (3.9±0.25mg.s-1) relaxations, whereas the more selective TRPC3 blocker Pyr10 (1 to 3µM) had no effect. The recently described TRPC4/5 selective blocker, ML204 (1 to 3µM), reverted completely acetylcholine relaxations, but minimally thapsigargin induced ones. Noteworthy, relaxations elicited by GSK1016790A (TRPV4 agonist) were unaffected by pyrazole compounds or ML204. After Pyr2 and Pyr6 pre-incubation, acetylcholine and thapsigargin evoked transient relaxations similar in magnitude and kinetics to those observed in the absence of extracellular calcium. Sodium nitroprusside relaxations as well as phenylephrine-induced contractions (denuded aorta) were not affected by any of pyrazole compounds (1 to 3µM). CONCLUSION: These observations revealed a previously unrecognized complexity in rat aorta endothelial calcium influx pathways, which result in production and release of nitric oxide. Pharmacologically distinguishable pathways mediate acetylcholine (ORAI/TRPC other than TRPC3/TRPC4 calcium-permeable channels) and thapsigargin (TRPC4 not required) induced calcium influx.


Subject(s)
Acetylcholine/pharmacology , Calcium/pharmacology , Endothelial Cells/drug effects , Endothelial Cells/metabolism , Endothelium-Dependent Relaxing Factors/metabolism , Nitric Oxide/metabolism , Thapsigargin/pharmacology , Animals , Aorta, Thoracic/drug effects , Calcium Release Activated Calcium Channels/metabolism , Male , Rats, Wistar , TRPC Cation Channels/metabolism , TRPV Cation Channels/drug effects , TRPV Cation Channels/metabolism , Time Factors , Vasodilator Agents/pharmacology
2.
Einstein (Säo Paulo) ; 17(3): eAO4600, 2019. graf
Article in English | LILACS | ID: biblio-1011991

ABSTRACT

ABSTRACT Objective: To characterize the calcium influx pathways implicated in the sustained elevation of endothelial intracellular calcium concentration, required for the synthesis and release of relaxing factors. Methods: We evaluated the effect of the newly synthesized pyrazole derivatives, described as selective inhibitors for ORAI (BTP2/Pyr2 and Pyr6) and TRPC3 (Pyr3 and Pyr10) channels, upon endothelium- and extracellular calcium-dependent relaxations stimulated by acetylcholine and thapsigargin, in pre-constricted rat thoracic aortic rings. Results: Acetylcholine and thapsigargin responses were completely reverted by Pyr2 and Pyr6 (1 to 3μM). Pyr3 (0.3 to 3μM) caused a rapid reversal of acetylcholine (6.2±0.08mg.s−1) and thapsigargin (3.9±0.25mg.s−1) relaxations, whereas the more selective TRPC3 blocker Pyr10 (1 to 3μM) had no effect. The recently described TRPC4/5 selective blocker, ML204 (1 to 3μM), reverted completely acetylcholine relaxations, but minimally thapsigargin induced ones. Noteworthy, relaxations elicited by GSK1016790A (TRPV4 agonist) were unaffected by pyrazole compounds or ML204. After Pyr2 and Pyr6 pre-incubation, acetylcholine and thapsigargin evoked transient relaxations similar in magnitude and kinetics to those observed in the absence of extracellular calcium. Sodium nitroprusside relaxations as well as phenylephrine-induced contractions (denuded aorta) were not affected by any of pyrazole compounds (1 to 3μM). Conclusion: These observations revealed a previously unrecognized complexity in rat aorta endothelial calcium influx pathways, which result in production and release of nitric oxide. Pharmacologically distinguishable pathways mediate acetylcholine (ORAI/TRPC other than TRPC3/TRPC4 calcium-permeable channels) and thapsigargin (TRPC4 not required) induced calcium influx.


RESUMO Objetivo: Caracterizar as vias do influxo de cálcio envolvidas no aumento sustentado da concentração intracelular de cálcio na célula endotelial, essencial para a síntese e a liberação de fatores relaxantes. Métodos: Analisamos o efeito de derivados pirazólicos sintetizados recentemente, descritos como inibidores seletivos para canais ORAI (BTP2/Pyr2 e Pyr6) e TRPC3 (Pyr3 e Pyr10), nos relaxamentos dependentes de endotélio e cálcio extracelular, produzidos por acetilcolina e tapsigargina, em anéis pré-contraídos da aorta torácica de rato. Resultados: As respostas de acetilcolina e tapsigargina foram completamente revertidas por Pyr2 e Pyr6 (1 a 3μM). Pyr3 (0,3 a 3μM) produziu reversão rápida dos relaxamentos de acetilcolina (6,2±0,08mg.s−1) e tapsigargina (3,9±0,25mg.s−1), enquanto o bloqueador mais seletivo para TRPC3, Pyr10 (1 a 3μM), não apresentou efeito. ML204 (1 a 3μM), bloqueador seletivo de TRPC4, descrito há pouco tempo, reverteu os relaxamentos induzidos por acetilcolina de forma completa, mas afetou minimamente aqueles produzidos por tapsigargina. Os derivados pirazólicos ou ML204 não afetaram os relaxamentos estimulados com GSK1016790A (TRPV4-agonista). Ainda, após pré-incubação com Pyr2 e Pyr6, acetilcolina e tapsigargina provocaram relaxamentos transitórios semelhantes em magnitude e cinética àqueles observados na ausência de cálcio extracelular. Os relaxamentos do nitroprussiato de sódio e as contrações induzidas pela fenilefrina (aorta sem endotélio) não foram afetados pelos compostos pirazólicos (1 a 3μM). Conclusão: Essas observações revelaram uma complexidade desconhecida das vias de influxo de cálcio no endotélio da aorta de rato, que resultam na produção e na liberação de óxido nítrico. Vias distinguíveis farmacologicamente medeiam o influxo estimulado por acetilcolina (ORAI TRPC, diferentes de TRPC3 TRPC4) e tapsigargina (TRPC4 não requerido).


Subject(s)
Animals , Male , Acetylcholine/pharmacology , Calcium/pharmacology , Thapsigargin/pharmacology , Endothelial Cells/drug effects , Endothelial Cells/metabolism , Endothelium-Dependent Relaxing Factors/metabolism , Nitric Oxide/metabolism , Aorta, Thoracic/drug effects , Time Factors , Vasodilator Agents/pharmacology , Rats, Wistar , TRPC Cation Channels/metabolism , TRPV Cation Channels/drug effects , TRPV Cation Channels/metabolism , Calcium Release Activated Calcium Channels/metabolism
3.
Medicina (Ribeiräo Preto) ; 51(2): 87-88, abr.-jun. 2018.
Article in Portuguese | LILACS | ID: biblio-979824

Subject(s)
Medicine , Education
4.
Einstein (Sao Paulo) ; 13(3): 395-403, 2015.
Article in English, Portuguese | MEDLINE | ID: mdl-26466063

ABSTRACT

OBJECTIVE: To describe and to characterize the relaxing effect of an extract of the bark of Combretum leprosum on isolated arterial rings from different animals. METHODS: Rings (3 to 4mm) from rabbit, rat, or porcine arteries rings were suspended in an organ bath (Krebs, 37°C, 95%O2/5%CO2) to record isometric contractions. After the stabilization period (2 to 3 hours) contractions were induced by the addition of phenylephrine (0.1 to 0.3µM) or U46619 (10 to 100nM), and Combretum leprosum extract was added on the plateau of the contractions. Experiments were performed to determine the potency, duration, reversibility, and to get insights on the potential mechanism involved in extract-induced relaxations. RESULTS: In all rings tested, Combretumleprosum extract (1.5µg/mL) was able to cause relaxations, which were strictly endothelium-dependent. In rabbit or rat thoracic aorta rings, the relaxations were reversed by vitamin B12a or L-NG-nitroarginine. In porcine right coronary arteries and rabbit abdominal aorta, extract caused both L-NG-nitroarginine-sensitive and L-NG-nitroarginine-resistant relaxations. In rabbit thoracic aorta, the extract was relatively potent (EC50=0.20µg/mL) and caused relaxations; intriguingly the endothelium continued to produce relaxing factors for a long period after removing the extract. The magnitude of extract-induced relaxations was significantly reduced in the absence of extracellular Ca2+; in addition, the TRPs channels blocker ruthenium red (10µM) was able to revert extract-induced relaxations. Phytochemical analyses indicated that the extract was rich in polyphenol-like reacting substances. CONCLUSIONS: Combretum leprosum extract contains bioactive compounds capable of promoting Ca2+-dependent stimulation of endothelial cells which results in a prolonged production of relaxing factors.


Subject(s)
Combretum/chemistry , Endothelium-Dependent Relaxing Factors/pharmacology , Muscle Relaxation/drug effects , Nitric Oxide/pharmacology , Acetylcholine/pharmacology , Animals , Aorta, Abdominal/drug effects , Aorta, Abdominal/physiology , Aorta, Thoracic/drug effects , Aorta, Thoracic/physiology , Carotid Artery, Common/drug effects , Carotid Artery, Common/physiology , Endothelium, Vascular/drug effects , Endothelium, Vascular/physiology , Female , Guinea Pigs , Male , Mesenteric Artery, Superior/drug effects , Mesenteric Artery, Superior/physiology , Mice , Muscle Relaxation/physiology , Plant Bark/chemistry , Rabbits , Rats, Wistar , Swine , Time Factors
5.
Einstein (Säo Paulo) ; 13(3): 395-403, July-Sep. 2015. graf
Article in English | LILACS | ID: lil-761966

ABSTRACT

Objective To describe and to characterize the relaxing effect of an extract of the bark of Combretum leprosum on isolated arterial rings from different animals.Methods Rings (3 to 4mm) from rabbit, rat, or porcine arteries rings were suspended in an organ bath (Krebs, 37°C, 95%O2/5%CO2) to record isometric contractions. After the stabilization period (2 to 3 hours) contractions were induced by the addition of phenylephrine (0.1 to 0.3µM) or U46619 (10 to 100nM), and Combretum leprosum extract was added on the plateau of the contractions. Experiments were performed to determine the potency, duration, reversibility, and to get insights on the potential mechanism involved in extract-induced relaxations.Results In all rings tested, Combretumleprosum extract (1.5μg/mL) was able to cause relaxations, which were strictly endothelium-dependent. In rabbit or rat thoracic aorta rings, the relaxations were reversed by vitamin B12a or L-NG-nitroarginine. In porcine right coronary arteries and rabbit abdominal aorta, extract caused both L-NG-nitroarginine-sensitive and L-NG-nitroarginine-resistant relaxations. In rabbit thoracic aorta, the extract was relatively potent (EC50=0.20µg/mL) and caused relaxations; intriguingly the endothelium continued to produce relaxing factors for a long period after removing the extract. The magnitude of extract-induced relaxations was significantly reduced in the absence of extracellular Ca2+; in addition, the TRPs channels blocker ruthenium red (10µM) was able to revert extract-induced relaxations. Phytochemical analyses indicated that the extract was rich in polyphenol-like reacting substances.ConclusionsCombretum leprosum extract contains bioactive compounds capable of promoting Ca2+-dependent stimulation of endothelial cells which results in a prolonged production of relaxing factors.


Objetivo Descrever e caracterizar os relaxamentos induzidos por um extrato das cascas de Combretum leprosum em anéis de artérias de diferentes espécies de animais.Métodos Anéis (3 a 4mm) de artérias de coelho, rato e porco foram montados em cubas para órgão isolado (Krebs, 37°C, 95%O2/5%CO2) para registro das contrações isométricas. Após um período de estabilização (2 a 3 horas), as contrações foram induzidas com fenilefrina (0,1 a 0,3µM) ou U46619 (10 a 100nM); no platô dessas contrações, adicionamos o extrato Combretum leprosum. Diferentes protocolos foram realizados para determinar potência, duração, reversibilidade e mecanismo dos relaxamentos induzidos pelo extrato.Resultados Em todas as preparações testadas, o extrato de Combretum leprosum (1,5µg/mL) provocou relaxamentos dependentes de endotélio. Em aorta torácica de coelho ou rato, os relaxamentos foram revertidos pela vitamina B12a ou L-NG-nitro-arginina. Em anéis de aorta abdominal de coelho e de artérias coronárias de porco, o extrato causou relaxamentos sensíveis e resistentes à L-NG-nitro-arginina. Em aorta torácica de coelho, o extrato foi relativamente muito potente (EC50=0,20μg/mL) e quando causou relaxamentos; intrigantemente o endotélio continuou a produzir fatores relaxantes por um longo período após remoção do extrato. A magnitude dos relaxamentos induzidos pelo extrato foi significativamente reduzida em ausência Ca2+ extracelular; ademais, o vermelho de rutênio (10μM), um bloqueador de canais TRPs, foi capaz de reverter os relaxamentos induzidos pelo extrato. Análises preliminares indicaram que o extrato continha compostos com reatividade química semelhante à polifenóis.Conclusão O extrato de Combretum leprosum contem compostos bioativos capazes de promover estimulação dependente de Ca2+ das células endoteliais a qual resulta numa produção prolongada de fatores relaxantes.


Subject(s)
Animals , Female , Guinea Pigs , Male , Mice , Rabbits , Combretum/chemistry , Endothelium-Dependent Relaxing Factors/pharmacology , Muscle Relaxation/drug effects , Nitric Oxide/pharmacology , Acetylcholine/pharmacology , Aorta, Abdominal/drug effects , Aorta, Abdominal/physiology , Aorta, Thoracic/drug effects , Aorta, Thoracic/physiology , Carotid Artery, Common/drug effects , Carotid Artery, Common/physiology , Endothelium, Vascular/drug effects , Endothelium, Vascular/physiology , Mesenteric Artery, Superior/drug effects , Mesenteric Artery, Superior/physiology , Muscle Relaxation/physiology , Plant Bark/chemistry , Rats, Wistar , Swine , Time Factors
6.
Einstein (Sao Paulo) ; 11(1): 88-94, 2013.
Article in English, Portuguese | MEDLINE | ID: mdl-23579750

ABSTRACT

OBJECTIVE: To determine the concentration of nitrate/nitrite in the cerebrospinal fluid and in the dorsal horn interstice of the L6-S1 spinal cord boundary in rats with or without cystitis induced by cyclophosphamide. METHODS: All experiments were conducted using Wistar female rats. A microdialysis probe was implanted in the subarachnoid space or in the spinal cord tissue at the L6-S1 segments (confirmed histologically). Two days later, the microdialysis probe was perfused with artificial cerebrospinal fluid, containing or not NG-monomethyl-L-arginine. Samples were collected every 15 minutes and kept at -20ºC. Nitrite/nitrate concentrations were determined by chemiluminescence. RESULTS: In normal animals, the mean values of nitrite/nitrate concentrations in the first microdialysate sample of the cerebrospinal fluid and of the spinal cord interstice were similar (482.5±90.2pmol/75µL, n=20, and 505.7±11.5pmol/75µL, n=6, respectively), whereas, in the samples from rats with cystitis, these values were significantly greater (955.5±66.3pmol/75µL, n=8, and 926.5±131.7pmol/75µL, n=11, respectively). In both groups, NG-monomethyl-L- arginine caused a significant reduction in the nitrite/nitrate concentration. Interestingly, the maximal reduction of nitrite/nitrate concentration caused by NG-monomethyl-L- arginine was no greater than 30% of the initial values. CONCLUSIONS: These results constitute the first demonstration that nitrite/nitrate concentrations in the cerebrospinal fluid and spinal cord interstice are elevated between 20- and 22 hours after cyclophosphamide-induced cystitis, and indicate that cystitis is associated with changes in the production of nitric oxide in the spinal cord segments, where most primary bladder afferents end.


Subject(s)
Cystitis/chemically induced , Nitric Oxide/metabolism , Spinal Cord/chemistry , Animals , Cyclophosphamide , Cystitis/metabolism , Cystitis/pathology , Female , Lumbosacral Region , Luminescence , Microdialysis , Nitrates/cerebrospinal fluid , Nitrates/metabolism , Nitric Oxide/cerebrospinal fluid , Nitric Oxide Synthase/antagonists & inhibitors , Nitrites/cerebrospinal fluid , Nitrites/metabolism , Rats , Rats, Wistar , Reference Values , Spinal Cord/metabolism , Time Factors , Urinary Bladder/metabolism , Urinary Bladder/pathology , omega-N-Methylarginine/pharmacology
7.
Einstein (Säo Paulo) ; 11(1): 88-94, jan.-mar. 2013. ilus, graf
Article in Portuguese | LILACS | ID: lil-670310

ABSTRACT

OBJETIVO: Determinar a concentração de nitrato/nitrito no líquido cefalorraquidiano e no interstício do corno dorsal entre L6-S1 da medula espinhal em ratas com ou sem cistite induzida por ciclofosfamida. MÉTODOS: Todos os experimentos foram conduzidos usando ratas Wistar. Um probe de microdiálise foi implantado no espaço subaracnoide ou no tecido da medula espinhal nos segmentos L6-S1 (confirmado histologicamente). Dois dias depois, o probe de microdiálise foi perfundido com líquido cefalorraquidiano artificial, contendo ou não NG-monometil-L-arginina. As amostras foram coletadas a cada 15 minutos e mantidas a -20ºC. As concentrações de nitrito/ nitrato foram determinadas por quimiluminescência. RESULTADOS: Nos animais normais, os valores médios das concentrações de nitrito/nitrato, na primeira amostra de microdialisado de líquido cefalorraquidiano e do interstício da medula espinhal, foram semelhantes (482,5±90,2pmol/75µL, n=20, e 505,7±11,5pmol/75µL, n=6, respectivamente), enquanto nas amostras de ratas com cistite, esses valores foram significativamente maiores (955,5±66,3pmol/75µL, n=8, e 926,5±131,7pmol/75µL, n=11, respectivamente). Em ambos os grupos, a NG-monometil-L- arginina causou uma significativa redução na concentração de nitrito/nitrato. Curiosamente, a redução máxima de concentração de nitrito/nitrato causada pela NG-monometil-L- arginina não foi maior que 30% dos valores iniciais. CONCLUSÕES: Esses resultados constituem a primeira demonstração de que as concentrações de nitrito/nitrato no líquido cefalorraquidiano e no interstício da medula espinhal estão elevadas entre 20 e 22 horas após a cistite induzida por ciclofosfamida, e indicando que a cistite está associada a alterações na produção de óxido nítrico, nos segmentos da medula espinhal, nos quais termina a maioria dos aferentes primários da bexiga.


OBJECTIVE: To determine the concentration of nitrate/nitrite in the cerebrospinal fluid and in the dorsal horn interstice of the L6-S1 spinal cord boundary in rats with or without cystitis induced by cyclophosphamide. METHODS: All experiments were conducted using Wistar female rats. A microdialysis probe was implanted in the subarachnoid space or in the spinal cord tissue at the L6-S1 segments (confirmed histologically). Two days later, the microdialysis probe was perfused with artificial cerebrospinal fluid, containing or not NG-monomethyl-L-arginine. Samples were collected every 15 minutes and kept at -20ºC. Nitrite/nitrate concentrations were determined by chemiluminescence. RESULTS: In normal animals, the mean values of nitrite/nitrate concentrations in the first microdialysate sample of the cerebrospinal fluid and of the spinal cord interstice were similar (482.5±90.2pmol/75µL, n=20, and 505.7±11.5pmol/75µL, n=6, respectively), whereas, in the samples from rats with cystitis, these values were significantly greater (955.5±66.3pmol/75µL, n=8, and 926.5±131.7pmol/75µL, n=11, respectively). In both groups, NG-monomethyl-L- arginine caused a significant reduction in the nitrite/nitrate concentration. Interestingly, the maximal reduction of nitrite/nitrate concentration caused by NG-monomethyl-L- arginine was no greater than 30% of the initial values. CONCLUSIONS: These results constitute the first demonstration that nitrite/nitrate concentrations in the cerebrospinal fluid and spinal cord interstice are elevated between 20- and 22 hours after cyclophosphamide-induced cystitis, and indicate that cystitis is associated with changes in the production of nitric oxide in the spinal cord segments, where most primary bladder afferents end.


Subject(s)
Cyclophosphamide , Cystitis/chemically induced , Microdialysis , Nitric Oxide , omega-N-Methylarginine
8.
Cancer Lett ; 212(1): 33-41, 2004 Aug 20.
Article in English | MEDLINE | ID: mdl-15246559

ABSTRACT

We determined whether alterations in the expression of p53, p16(INK4) and p21(WAF1/CIP1) influence the invasiveness of a subset of gastric adenocarcinomas co-expressing TGFalpha and EGFR. Immunopositivity for TGFalpha-EGFR (26%) was observed in both early and advanced adenocarcinomas, and 88% of these showed immunoreactivity for p53. SSCP analysis revealed that in 81% of these tumors the p53 gene was mutated in exons 5-8. The intensity of p53 immunoreactivity was significantly higher (P < 0.013) in deeply invasive tumors. p16(INK4) and p21(WAF1/CIP1) immunoreactivity was detected in 93 and 76% of the samples co-expressing TGFalpha-EGFR but the levels were not correlated with those of p53 and other clinico-pathological parameters. We conclude that gastric adenocarcinomas potentially dependent upon the TGFalpha-EGFR autocrine loop for growing exhibit increased aggressiveness in the presence of aberrant p53.


Subject(s)
Adenocarcinoma/genetics , Adenocarcinoma/pathology , ErbB Receptors/biosynthesis , Genes, p53 , Neoplasm Invasiveness , Stomach Neoplasms/genetics , Stomach Neoplasms/pathology , Transforming Growth Factor alpha/biosynthesis , Cyclin-Dependent Kinase Inhibitor p16/biosynthesis , Cyclin-Dependent Kinase Inhibitor p16/pharmacology , Cyclin-Dependent Kinase Inhibitor p21 , Cyclins/biosynthesis , Cyclins/pharmacology , DNA Mutational Analysis , Enzyme Inhibitors/pharmacology , Humans , Immunohistochemistry , Signal Transduction
9.
Hypertension ; 42(4): 802-5, 2003 Oct.
Article in English | MEDLINE | ID: mdl-12913062

ABSTRACT

The present study evaluated the potential mechanism involved in the hypotensive effect induced by ET-1 in rats treated with the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) in the drinking water during 7 days. Hypertension developed in the L-NAME-treated rats (164+/-3 versus 112+/-1 mm Hg in untreated control rats), and the hypotensive effect of ET-1 (100 pmol/kg IV) was significantly enhanced compared with control rats (32+/-2% versus 20+/-1% fall in mean arterial pressure). The enhanced ET-1 hypotensive effect in L-NAME-treated rats was abolished by the ETB receptor antagonist BQ-788 but was unaltered by the cyclooxygenase inhibitor diclofenac, the cytochrome P450 inhibitor fluconazole, or the potassium channel blockers apamin, glibenclamide, tetraethylammonium, and 4-aminopyridine. Pretreatment with the cannabinoid CB1 receptor antagonist SR141716A significantly reduced the hypotensive response to ET-1 in L-NAME-treated rats (20+/-1%), although it did not modify the response in untreated control rats (17+/-1%). These findings indicate that in rats under chronic NOS inhibition, the hypotensive effect of ET-1 is unexpectedly enhanced and appears to be mediated by a non-NO/non-prostanoid mechanism and involves an SR141716A-sensitive mechanism triggered by ETB receptor activation.


Subject(s)
Endothelin-1/pharmacology , Nitric Oxide Synthase/antagonists & inhibitors , Receptors, Drug/antagonists & inhibitors , Vasodilator Agents/pharmacology , Animals , Blood Pressure/drug effects , Drug Synergism , Enzyme Inhibitors/pharmacology , Heart Rate/drug effects , Hypertension/chemically induced , Hypertension/physiopathology , Male , NG-Nitroarginine Methyl Ester/pharmacology , Rats , Rats, Wistar , Receptors, Cannabinoid
10.
Life Sci ; 70(26): 3131-42, 2002 May 17.
Article in English | MEDLINE | ID: mdl-12008096

ABSTRACT

Late pregnancy in rats is characterized by a decrease in arterial pressure and in isolated arterial vessels response to vasoconstrictors. In uterine arteries the pregnancy-associated attenuation of the response to vasoconstrictors has been attributed to an increase in basal and agonist-induced endothelial NO production. However, the role of NO in pregnancy-associated changes of systemic arteries reactivity to vasoactive agents remains to be fully elucidated. We examined whether pregnancy influences the reactivity of systemic arteries to vasodilator or vasoconstrictor agents through NO-dependent mechanisms. Thoracic aortic rings and mesenteric arterial bed of late pregnant rats showed refractoriness to phenylephrine-induced vasoconstriction that was abolished by NO synthase inhibition. The potency of L-NNA to enhance tension of aortic rings preconstricted with phenylephrine (10-20% of their maximal response) was significantly lower in preparations from pregnant animals. In phenylephrine-contracted aortas and mesenteric bed, the effects of the endothelium-dependent vasodilators acetylcholine, A23187 and bradykinin, were not influenced by pregnancy. Similarly, pregnancy did not affect the vasodilator responses of adenosine, isoproterenol, capsaicin, nitroprusside, forskolin, and Hoe234 in the mesenteric bed. NO synthase activity measured by determining the conversion of L-[(3)H]-arginine to L-[(3)H]-citrulline in aorta and mesenteric arteries homogenates was not altered by pregnancy. These findings show that endothelial-dependent and -independent vasodilators action as well as NO synthase activity in systemic arteries is uninfluenced by pregnancy, whereas pregnancy-associated hyporeactivity of systemic arteries to vasoconstrictors is related to an enhanced endothelial NO production either spontaneous or elicited directly or indirectly by vasoconstrictor agents. This interpretation implies that the enhanced NO production observed in systemic arteries during late pregnancy involves cellular pathways other than the ones involved in the response to endothelium-dependent vasodilators such as acetylcholine.


Subject(s)
Aorta, Thoracic/metabolism , Mesenteric Arteries/metabolism , Nitric Oxide/metabolism , Pregnancy, Animal/physiology , Animals , Aorta, Thoracic/drug effects , Dose-Response Relationship, Drug , Female , Mesenteric Arteries/drug effects , Nitric Oxide Synthase/metabolism , Nitric Oxide Synthase Type III , Pregnancy , Rats , Rats, Wistar , Vasoconstriction/drug effects , Vasoconstrictor Agents/pharmacology , Vasodilation/drug effects , Vasodilator Agents/pharmacology
11.
Obstet. ginecol. latinoam ; 43(9/10): 289-92, set.-oct. 1985. Tab
Article in Spanish | BINACIS | ID: bin-32922

ABSTRACT

Cuatro grupos de ratas en el dia 19 de la gestación fueron injectadas con 3H-trimetoquinol (Inolin-R) intravenoso en dosis de 4,3 uCi/kg de peso (actividad específica 17.18 mCi/nM). Los 4 grupos de animales fueron sacrificados a diferentes intervalos post-inyección: 5, 15, 30 y 60 minutos respectivamente. Al cabo de dichos tiempos, se estudió la distribución de la droga en los tejidos maternos y fetales: hígado, pulmón, riñón, orina y plasma maternos, placenta, líquido amniótico, sangre e hígado fetales, importantes niveles de radiactividad fueron encontrados a nivel fetal, demostrando el pasaje placentario de la droga (AU)


Subject(s)
Pregnancy , Rats , Animals , Female , Obstetric Labor, Premature/prevention & control , Maternal-Fetal Exchange , Tretoquinol/therapeutic use
12.
Obstet. ginecol. latinoam ; 43(9/10): 289-92, set.-oct. 1985. tab
Article in Spanish | LILACS | ID: lil-28521

ABSTRACT

Cuatro grupos de ratas en el dia 19 de la gestación fueron injectadas con 3H-trimetoquinol (Inolin-R) intravenoso en dosis de 4,3 uCi/kg de peso (actividad específica 17.18 mCi/nM). Los 4 grupos de animales fueron sacrificados a diferentes intervalos post-inyección: 5, 15, 30 y 60 minutos respectivamente. Al cabo de dichos tiempos, se estudió la distribución de la droga en los tejidos maternos y fetales: hígado, pulmón, riñón, orina y plasma maternos, placenta, líquido amniótico, sangre e hígado fetales, importantes niveles de radiactividad fueron encontrados a nivel fetal, demostrando el pasaje placentario de la droga


Subject(s)
Pregnancy , Rats , Animals , Female , Maternal-Fetal Exchange , Obstetric Labor, Premature/prevention & control , Tretoquinol/therapeutic use
13.
Obstet. ginecol. latinoam ; 41(1/2): 1-4, 1983.
Article in Spanish | BINACIS | ID: bin-35004

ABSTRACT

En una poblacion de 81 embarazadas seleccionadas al azar, se analizo el valor de la determinacion de la presion arterial media (PAM) en el segundo trimestre, como indicador predictivo de hipertension inducida por el embarazo (H.I.E). La incidencia de H.I.E. en la poblacion estudiada fue de 19,8% de Frecuencia Relativa (F.R.) y el promedio de la PAM en el 2o. trimestre fue mas elevado en las gestantes que presentaron posteriormente H.I.E. (p < 0.001) (Prueba de Student). Al considerar unicamente las primigestas donde ocurrio la mayor incidencia de H.I.E. (F.R. 31%) la relacion de su PAM en el 2o. trimestre con respecto al valor critico de 90 mm.Hg.se observo que las gestantes cuyas PAM fueran iguales o superiores a este valor critico, presentaron mayor incidencia de HIE. Esta asociacion es estadisticamente significativa (p = 0,0225) (Prueba de Fischer). Se sugiere la determinacion de rutina de la PAM como metodo sencillo de deteccion de la H.I.E. en los consultorios prenatales, incluyendo los de nivel primario de salud


Subject(s)
Pregnancy , Humans , Female , Pregnancy Complications , Blood Pressure Determination , Hypertension
14.
Obstet. ginecol. latinoam ; 41(1/2): 1-4, 1983.
Article in Spanish | LILACS | ID: lil-14944

ABSTRACT

En una poblacion de 81 embarazadas seleccionadas al azar, se analizo el valor de la determinacion de la presion arterial media (PAM) en el segundo trimestre, como indicador predictivo de hipertension inducida por el embarazo (H.I.E). La incidencia de H.I.E. en la poblacion estudiada fue de 19,8% de Frecuencia Relativa (F.R.) y el promedio de la PAM en el 2o. trimestre fue mas elevado en las gestantes que presentaron posteriormente H.I.E. (p < 0.001) (Prueba de Student). Al considerar unicamente las primigestas donde ocurrio la mayor incidencia de H.I.E. (F.R. 31%) la relacion de su PAM en el 2o. trimestre con respecto al valor critico de 90 mm.Hg.se observo que las gestantes cuyas PAM fueran iguales o superiores a este valor critico, presentaron mayor incidencia de HIE. Esta asociacion es estadisticamente significativa (p = 0,0225) (Prueba de Fischer). Se sugiere la determinacion de rutina de la PAM como metodo sencillo de deteccion de la H.I.E. en los consultorios prenatales, incluyendo los de nivel primario de salud


Subject(s)
Pregnancy , Humans , Female , Blood Pressure Determination , Hypertension , Pregnancy Complications
15.
Bol. Oficina Sanit. Panam ; 90(1): 69-79, 1981.
Article in Spanish | LILACS | ID: lil-4651

ABSTRACT

La tecnologia apropiada para la atencion del parto normal permite vigilar el progreso del mismo sin interferir en su fisiologia ni en las relaciones del grupo familiar. Con este fin, se promueve la participacion activa de ambos padres, la adopcion de posiciones naturales y comodas para la madre, como tambien la realizacion espontanea de los esfuerzos expulsivos. Asimismo, se evitam las maniobras y medicaciones innecesarias, que interfieren tanto en el proceso natural del parto, como en la interaccion precoz de la madre con el recien nacido


Subject(s)
Parturition
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