RESUMEN
Postpartum uterine infections of dairy cows promote a local and systemic inflammation and interfere with reproductive efficiency. The aim of this study was to evaluate the effect of steroid hormones including progesterone (P4) and estradiol (E2) on the systemic inflammatory response of cows after being challenged with an intrauterine infusion of lipopolysaccharide (LPS). For this, a hemogram and serum dosage of haptoglobin (Hp) in eight primiparous Gir cows ovariectomized were performed on day (day 0) and after 24 h (day +1). Four cows (n = 4) were challenged (day 0) with 20 mL of 0.9% NaCl + 12.5 µg/kg LPS, and four cows (n = 4) were challenged (day 0) with 20 mL of 0.9% NaCl. For this, the study was divided in four experimental groups as: (1) Control group: without any hormonal treatment before day 0; (2) Group 24 h - E2: 1 mg of estradiol benzoate 24 h before (day -1); (3) Group 24 h - P4: 2.0 g of P4 device 24 h before (day -1); (4) Group 14 d - P4: 2.0 g of P4 device 14 days before (day -14). In the systemic response to LPS, there was an increase in Hp (control group; 24 h - P4 group; 14 d - P4 group), and on day +1 the Hp of 14 d - P4 group was higher when compared to the other groups. On day 0, the 14 d - P4 group had an increase in circulating leukocytes and lymphocytes cells than the control group (P < 0.01). On day +1 after LPS-challenge the 14 d - P4 group showed a decrease in circulating lymphocytes, eosinophils, and monocytes (P < 0.05). A neutrophilia with left shift in the two treatments with P4 (day +1), in addition to a thrombocytopenia and lower platelets compared to the 24 h - E2 group (P < 0.05) (day 0) were recorded. It was concluded that ovariectomized cows challenged with LPS, previously submitted to steroid hormones induce a systemic inflammatory response. Also, the systemic response is more intense after previous prolonged exposure to P4 and less intense after exposure to E2. This study provided important information relating the effect of ovarian steroids on the systemic inflammatory response of cows challenged with intrauterine LPS.
Asunto(s)
Enfermedades de los Bovinos , Lipopolisacáridos , Animales , Bovinos , Enfermedades de los Bovinos/tratamiento farmacológico , Estradiol , Femenino , Lipopolisacáridos/farmacología , Ovario , Progesterona , Reproducción , Síndrome de Respuesta Inflamatoria Sistémica/veterinariaRESUMEN
The present study investigated the role of several 5-HT receptor subtypes in the lateral parabrachial nucleus (LPBN) in the control of sodium appetite (i.e. NaCl consumption). Male Holtzman rats had cannulas implanted bilaterally into the LPBN for the injection of 5-HT receptor agonists and antagonists in conjunction with either acute fluid depletion or 24-h sodium depletion. Following these treatments, access to 0.3 M NaCl was provided and the intakes of saline and water were measured for the next 2 h. Bilateral injections of the 5-HT2A receptor antagonist, ketanserin or the 5-HT2C receptor antagonist, mianserin into the LPBN increased 0.3 M NaCl intake without affecting water intake induced by acute fluid-depletion. Bilateral injections of the 5-HT2B receptor agonist, BW723C86 hydrochloride, had no effect on 0.3 M NaCl or water intake under these conditions. Treatment of the LPBN with the 5-HT2B/2C receptor agonist, 2-(2-methyl-4-clorophenoxy) propanoic acid (mCPP) caused dose-related reductions in 0.3 M NaCl intake after 24 h sodium depletion. The effects of mCPP were prevented by pretreating the LPBN with the 5-HT2B/2C receptor antagonist, SDZSER082. Activation of 5-HT3 receptors by the receptor agonist, 1-phenylbiguanide (PBG) caused dose-related increases in 0.3 M NaCl intake. Pretreatment of the LPBN with the 5-HT3 receptor antagonist, 1-methyl-N-[8-methyl-8-azabicyclo (3.2.1)-oct-3-yl]-1H-indazole-3-carboxamide (LY-278,584) abolished the effects of PBG, but LY-278,584 had no effects on sodium or water intake when injected by itself. PBG injected into the LPBN did not alter intake of palatable 0.06 M sucrose in fluid replete rats. The results suggest that activation of the 5-HT2A and 5-HT2C receptor subtypes inhibits sodium ingestion. In contrast, activation of the 5-HT3 receptor subtype increases sodium ingestion. Therefore, multiple serotonergic receptor subtypes in the LPBN are implicated in the control of sodium intake, sometimes by mediating opposite effects of 5-HT. The results provide new information concerning the control of sodium intake by LPBN mechanisms.
Asunto(s)
Conducta de Ingestión de Líquido/fisiología , Puente/metabolismo , Receptores de Serotonina 5-HT2/fisiología , Receptores de Serotonina 5-HT3/fisiología , Cloruro de Sodio/metabolismo , Animales , Conducta Animal , Relación Dosis-Respuesta a Droga , Ingestión de Líquidos/efectos de los fármacos , Conducta de Ingestión de Líquido/efectos de los fármacos , Interacciones Farmacológicas , Ketanserina/farmacología , Masculino , Modelos Biológicos , Puente/efectos de los fármacos , Ratas , Antagonistas de la Serotonina/farmacología , Agonistas de Receptores de Serotonina/farmacologíaRESUMEN
Inhibitory serotonergic and cholecystokinergic mechanisms in the lateral parabrachial nucleus and central GABAergic mechanisms are involved in the regulation of water and NaCl intake. In the present study we investigated if the GABA(A) receptors in the lateral parabrachial nucleus are involved in the control of water, NaCl and food intake in rats. Male Holtzman rats with stainless steel cannulas implanted bilaterally into the lateral parabrachial nucleus were used. Bilateral injections of muscimol (0.2 nmol/0.2 microl) into the lateral parabrachial nucleus strongly increased 0.3 M NaCl (20.3+/-7.2 vs. saline: 2.6+/-0.9 ml/180 min) without changing water intake induced by the treatment with the diuretic furosemide combined with low dose of the angiotensin converting enzyme inhibitor captopril s.c. In euhydrated and satiated rats, bilateral lateral parabrachial nucleus injections of muscimol (0.2 and 0.5 nmol/0.2 microl) induced 0.3 M NaCl intake (12.1+/-6.5 and 32.5+/-7.3 ml/180 min, respectively, vs. saline: 0.4+/-0.2 ml/180 min) and water intake (5.2+/-2.0 and 7.6+/-2.8 ml/180 min, respectively, vs. saline: 0.8+/-0.4 ml/180 min), but no food intake (2+/-0.4 g/240 min vs. saline: 1+/-0.3 g/240 min). Bilateral lateral parabrachial nucleus injections of the GABA(A) antagonist bicuculline (1.6 nmol/0.2 microl) abolished the effects of muscimol (0.5 nmol/0.2 microl) on 0.3 M NaCl and water intake. Muscimol (0.5 nmol/0.2 microl) into the lateral parabrachial nucleus also induced a slight ingestion of water (4.2+/-1.6 ml/240 min vs. saline: 1.1+/-0.3 ml/240 min) when only water was available, a long lasting (for at least 2 h) increase on mean arterial pressure (14+/-4 mm Hg, vs. saline: -1+/-1 mm Hg) and only a tendency to increase urinary volume and Na+ and K+ renal excretion. Therefore the activation of GABA(A) receptors in the lateral parabrachial nucleus induces strong NaCl intake, a small ingestion of water and pressor responses, without changes on food intake.
Asunto(s)
Ingestión de Líquidos/fisiología , Ingestión de Alimentos/fisiología , Puente/fisiología , Receptores de GABA-A/fisiología , Solución Salina Hipertónica/metabolismo , Análisis de Varianza , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Animales , Conducta Animal , Bicuculina/farmacología , Presión Sanguínea/efectos de los fármacos , Captopril/farmacología , Diuresis/efectos de los fármacos , Diuréticos/farmacología , Ingestión de Líquidos/efectos de los fármacos , Interacciones Farmacológicas , Ingestión de Alimentos/efectos de los fármacos , Furosemida/farmacología , Agonistas del GABA/farmacología , Antagonistas del GABA/farmacología , Frecuencia Cardíaca/efectos de los fármacos , Masculino , Muscimol/farmacología , Puente/efectos de los fármacos , Potasio/orina , Ratas , Ratas Sprague-Dawley , Sodio/orina , Factores de TiempoRESUMEN
Serotonin antagonism in the lateral parabrachial nucleus (LPBN) enhances sodium appetite induced by hypovolaemia and angiotensin-mineralocorticoid activation, but produces no sodium intake in euhydrated animals. In the present work, male adult rats (n=21) that received bilateral injections of the serotonergic antagonist methysergide (4 microg/0.2 microl) into the LPBN combined to intragastric load of 2 M NaCl (2 ml/rat), ingested hypertonic NaCl (ingestion of 4.3 +/- 1.6 ml/2 h of 0.3 M NaCl versus vehicle into LPBN: 0.2 +/- 0.2 ml/2 h, P<0.05). Methysergide- and vehicle-treated animals also ingested water (9.5 +/- 0.7 and 7.2+/-0.5 ml/2 h, respectively, P>0.05) as expected from the state of cell dehydration produced by the load. Ingestion of water (11.0 +/- 1.2 ml/2 h), and of 0.3 M NaCl (1.1 +/- 0.7 ml/2 h) were not altered by methysergide in NaCl loaded rats with misplaced LPBN injections (n=15).The ingestion of hypertonic NaCl by rats with serotonergic blockade in the LPBN suggests that the circuits subserving sodium appetite are activated, but at the same time strongly inhibited through the LPBN, during cell dehydration.
Asunto(s)
Apetito/fisiología , Encéfalo/metabolismo , Antagonistas de la Serotonina/farmacología , Cloruro de Sodio Dietético/metabolismo , Equilibrio Hidroelectrolítico/fisiología , Animales , Apetito/efectos de los fármacos , Encéfalo/efectos de los fármacos , Deshidratación/metabolismo , Deshidratación/fisiopatología , Masculino , Metisergida/farmacología , Vías Nerviosas/efectos de los fármacos , Vías Nerviosas/fisiología , Puente/efectos de los fármacos , Puente/fisiología , Ratas , Ratas Sprague-Dawley , Solución Salina Hipertónica/metabolismo , Serotonina/metabolismo , Sed/efectos de los fármacos , Sed/fisiología , Equilibrio Hidroelectrolítico/efectos de los fármacosRESUMEN
Water and NaCl intake is strongly inhibited by the activation of alpha(2)-adrenergic receptors with clonidine or moxonidine (alpha(2)-adrenergic/imidazoline agonists) injected peripherally or into the forebrain and by serotonin and cholecystokinin in the lateral parabrachial nucleus (LPBN). Considering that alpha(2)-adrenergic receptors exist in the LPBN and the similar origin of serotonergic and adrenergic afferent pathways to the LPBN, in this study we investigated the effects of bilateral injections of moxonidine alone or combined with RX 821002 (alpha(2)-adrenergic antagonist) into the LPBN on 1.8% NaCl and water intake induced by the treatment with s.c. furosemide (10mg/kg)+captopril (5 mg/kg). Additionally, we investigated if moxonidine into the LPBN would modify furosemide+captopril-induced c-fos expression in the forebrain. Male Holtzman rats with cannulas implanted bilaterally in the LPBN were used. Contrary to forebrain injections, bilateral LPBN injections of moxonidine (0.1, 0.5 and 1 nmol/0.2 microl) strongly increased furosemide+captopril-induced 1.8% NaCl intake (16.6+/-2.7, 44.5+/-3.2 and 44.5+/-4.3 ml/2 h, respectively, vs. vehicle: 6.9+/-1.5 ml/2 h). Only the high dose of moxonidine increased water intake (23.3+/-3.8 ml/2 h, vs. vehicle: 12.1+/-2.6 ml/2 h). Prior injections of RX 821002 (10 and 20 nmol/0.2 microl) abolished the effect of moxonidine (0.5 nmol) on 1.8% NaCl intake. Moxonidine into the LPBN did not modify furosemide+captopril-induced c-fos expression in forebrain areas related to the control of fluid-electrolyte balance. The results show that the activation of LPBN alpha(2)-adrenergic receptors enhances furosemide+captopril-induced 1.8% NaCl and water intake. This enhancement was not related to prior alteration in the activity of forebrain areas as suggested by c-fos expression. Previous and present results indicate opposite roles for alpha(2)-adrenergic receptors in the control of sodium and water intake according to their distribution in the rat brain.
Asunto(s)
Apetito/fisiología , Conducta de Ingestión de Líquido/fisiología , Idazoxan/análogos & derivados , Puente/metabolismo , Receptores Adrenérgicos alfa 2/metabolismo , Cloruro de Sodio Dietético/metabolismo , Antagonistas Adrenérgicos alfa/administración & dosificación , Animales , Antihipertensivos/administración & dosificación , Presión Sanguínea , Captopril/farmacología , Diuréticos/farmacología , Furosemida/farmacología , Genes fos/efectos de los fármacos , Idazoxan/administración & dosificación , Imidazoles/administración & dosificación , Inmunohistoquímica , Masculino , Puente/efectos de los fármacos , Prosencéfalo/efectos de los fármacos , Prosencéfalo/metabolismo , RatasRESUMEN
Angiotensin II (Ang II) non-peptide antagonists were injected i.c.v. (6.25-200 nmol, n = 5-8 rats/group). In sodium replete rats, losartan (AT1 receptor antagonist) induced an increase in mean arterial pressure (MAP) and in heart rate (HR) by 3rd ventricular (3rdV) injection, and an weaker pressor response and bradycardia by 4th ventricular (4thV) injection. PD123319 (AT2 receptor antagonist) induced an increase in MAP and in HR by 3rdV injection, and an increase in MAP and no alteration in HR by 4thV injection. In sodium deplete (furosemide plus removal of ambient sodium for 24 h) rats, losartan induced an increase in MAP and no alteration in HR by 3rdV injection, and no alteration in MAP and bradycardia by 4thV injection. PD123319 induced an increase in MAP and in HR by 3rdV injection, and an increase in MAP and bradycardia by 4thV injection. Thus, there were no fall in MAP by central injections of Ang II antagonists. Intravenous injection of losartan, but not of PD123319, induced a fall in MAP in both sodium replete and sodium deplete animals. Therefore, losartan and PD123319 can have similar effects on MAP and HR when injected intracerebroventricularly, although some differences are also present. The bradycardia is consistent with an withdrawal of Ang II inhibitory action on baroreflex.
Asunto(s)
Antagonistas de Receptores de Angiotensina , Compuestos de Bifenilo/farmacología , Presión Sanguínea/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Imidazoles/farmacología , Piridinas/farmacología , Sodio/deficiencia , Tetrazoles/farmacología , Animales , Compuestos de Bifenilo/administración & dosificación , Presión Sanguínea/fisiología , Estudios de Cohortes , Frecuencia Cardíaca/fisiología , Imidazoles/administración & dosificación , Inyecciones Intraventriculares , Losartán , Masculino , Piridinas/administración & dosificación , Ratas , Tetrazoles/administración & dosificaciónRESUMEN
It has been shown that central or peripheral injections of the peptide relaxin induces water intake, not sodium intake in rats. Important inhibitory mechanisms involving serotonin and other neurotransmitters in the control of water and NaCl intake have been demonstrated in the lateral parabrachial nucleus (LPBN). In the present study, we investigated the effects of bilateral injections of methysergide (serotonergic receptor antagonist) into the LPBN on intracerebroventricular (i.c.v.) relaxin-induced water and NaCl intake in rats. Additionally, the effect of the blockade of central angiotensin AT(1) receptors with i.c.v. losartan on relaxin-induced water and NaCl intake in rats treated with methysergide into the LPBN was also investigated. Male Holtzman rats with cannulas implanted into the lateral ventricle (LV) and bilaterally in the LPBN were used. Intracerebroventricular injections of relaxin (500 ng/1 microl) induced water intake (5.1+/-0.7 ml/120 min), but not significant 1.8% NaCl intake (0.5+/-0.4 ml/120 min). Bilateral injections of methysergide (4 microg/0.2 microl) into the LPBN strongly stimulated relaxin-induced 1.8% NaCl intake (34.5+/-10.9 ml/120 min) and slightly increased water intake (10.5+/-4.9 ml/120 min). The pretreatment with i.c.v. losartan (100 microg/1 microl) abolished the effects of i.c.v. relaxin combined with LPBN methysergide on 1.8% NaCl intake (0.5+/-0.4 ml/120 min). Losartan (100 microg/1 microl) also abolished relaxin-induced water intake in rats injected with methysergide into the LPBN (1.6+/-0.8 ml/120 min) or not (0.5+/-0.3 ml/120 min). Losartan (50 microg/1 microl) partially reduced the effects of relaxin. The results show that central relaxin interacting with central angiotensinergic mechanisms induces NaCl intake after the blockade of LPBN serotonergic mechanisms.
Asunto(s)
Puente/fisiología , Relaxina/farmacología , Serotonina/fisiología , Cloruro de Sodio/farmacología , Sed/fisiología , Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacología , Animales , Ingestión de Líquidos/efectos de los fármacos , Ingestión de Líquidos/fisiología , Interacciones Farmacológicas , Inyecciones Intraventriculares , Losartán/farmacología , Masculino , Metisergida/farmacología , Puente/citología , Puente/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Receptor de Angiotensina Tipo 1/fisiología , Antagonistas de la Serotonina/farmacología , Sed/efectos de los fármacosRESUMEN
The effect of intravenous infusion of hypertonic saline (HS, 7.5% NaCl) on the recovery of mean arterial pressure (MAP) during hemorrhage was studied in sham-operated rats and in rats with electrolytic lesion in the anteroventral third ventricle (AV3V) region. After intravenous infusion of 7.5% NaCl (4 ml/kg b.wt.), MAP increased from about 60 to 90 mmHg in sham rats and became stable at this level during all the time of observation (30 min). In AV3V-lesioned rats, after the same infusion, the MAP increased to 80 mmHg, but returned to the pre-infusion levels within 30 min. These results show that the integrity of the AV3V region is important for the beneficial effect of HS during hemorrhagic shock in rats. The AV3V lesion disrupts neural pathways involved in the maintenance of fluid balance and these changes probably abolish the effect of hypertonic saline.
Asunto(s)
Ventrículos Cerebrales/fisiología , Soluciones Hipertónicas/uso terapéutico , Choque Hemorrágico/tratamiento farmacológico , Animales , Presión Sanguínea/efectos de los fármacos , Masculino , Ratas , Choque Hemorrágico/fisiopatologíaRESUMEN
The effect of intravenous infusion of hypertonic saline (HS, 7.5% NaCl) on the recovery of mean arterial pressure (MAP) after hemorrhage was studied in sham-operated rats and in rats with electrolytic lesion of the anteroventral third ventricle (AV3V) region (4 h, 4 and 20 days). Rats anesthetized with thiopental sodium were bled (about 2.8 ml/100 g) until the MAP was stabilized at the level of 60 mmHg for 30 min. In sham-lesioned rats, MAP increased to 90 mmHg and became stable near this level after intravenous infusion of 7.5% NaCl (4 ml/kg b.wt.). In AV3V-lesioned rats, the same infusion induced a smaller increase in MAP (80 mmHg) and the MAP returned to pre-infusion levels within 30 min. These results show that the AV3V region plays an important role in the recovery of arterial pressure induced by hypertonic saline in rats submitted to hemorrhagic shock.
Asunto(s)
Presión Sanguínea/fisiología , Ventrículos Cerebrales/fisiología , Choque Hemorrágico/fisiopatología , Animales , Presión Sanguínea/efectos de los fármacos , Encéfalo/patología , Ventrículos Cerebrales/patología , Hematócrito , Masculino , Miocardio/patología , Potasio/sangre , Ratas , Ratas Endogámicas , Solución Salina Hipertónica , Sodio/sangreRESUMEN
In the present study, we investigated the effect of previous injection of either prazosin (alpha 1-adrenergic antagonist) or atropine (muscarinic cholinergic antagonist) into the medial septal area (MSA) on the pressor and dipsogenic response induced by intracerebroventricular (ICV) injection of carbachol (cholinergic agonist) and angiotensin II (ANGII) in rats. The pressor and dipsogenic responses to ICV carbachol (7 nmol) were reduced after previous treatment of the MSA with atropine (0.5 to 5 nmol), but not prazosin (20 and 40 nmol). The dipsogenic response to ICA ANGII (25 ng) was reduced after prazosin (40 nmol) into the MSA. The pressor response to ICV ANGII was not changed either by previous treatment of the MSA with prazosin or atropine. The present results suggest a dissociation among the pathways subserving the control of dipsogenic and pressor responses to central cholinergic or angiotensinergic activation.
Asunto(s)
Angiotensina II/farmacología , Vías Autónomas/fisiología , Presión Sanguínea/efectos de los fármacos , Carbacol/farmacología , Ingestión de Líquidos/efectos de los fármacos , Sistema Nervioso Parasimpático/fisiología , Sistema Nervioso Simpático/fisiología , Angiotensina II/administración & dosificación , Angiotensina II/antagonistas & inhibidores , Animales , Atropina/farmacología , Encéfalo/anatomía & histología , Encéfalo/fisiología , Carbacol/administración & dosificación , Carbacol/antagonistas & inhibidores , Inyecciones Intraventriculares , Masculino , Prazosina/farmacología , RatasRESUMEN
Losartan, an AT1 angiotensin II (ANG II) receptor non-peptide antagonist, induces an increase in mean arterial pressure (MAP) when injected intracerebroventricularly (icv) into rats. The present study investigated possible effector mechanisms of the increase in MAP induced by icv losartan in unanesthetized rats. Male Holtzman rats (280-300 g, N = 6/group) with a cannula implanted into the anterior ventral third ventricle received an icv injection of losartan (90 micro g/2 micro l) that induced a typical peak pressor response within 5 min. In one group of animals, this response to icv losartan was completely reduced from 18 +/- 1 to 4 +/- 2 mmHg by intravenous (iv) injection of losartan (2.5-10 mg/kg), and in another group, it was partially reduced from 18 +/- 3 to 11 +/- 2 mmHg by iv prazosin (0.1-1.0 mg/kg), an alpha1-adrenergic antagonist (P<0.05). Captopril (10 mg/kg), a converting enzyme inhibitor, injected iv in a third group inhibited the pressor response to icv losartan from 24 +/- 3 to 7 +/- 2 mmHg (P<0.05). Propranolol (10 mg/kg), a beta-adrenoceptor antagonist, injected iv in a fourth group did not alter the pressor response to icv losartan. Plasma renin activity and serum angiotensin-converting enzyme activity were not altered by icv losartan in other animals. The results suggest that the pressor effect of icv losartan depends on angiotensinergic and alpha1-adrenoceptor activation, but not on increased circulating ANG II.
Asunto(s)
Agonistas alfa-Adrenérgicos/farmacología , Antagonistas de Receptores de Angiotensina , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Antihipertensivos/farmacología , Hipertensión/sangre , Losartán/farmacología , Peptidil-Dipeptidasa A/sangre , Renina/sangre , Animales , Antihipertensivos/administración & dosificación , Antihipertensivos/antagonistas & inhibidores , Presión Sanguínea/efectos de los fármacos , Hipertensión/inducido químicamente , Inyecciones Intraventriculares , Losartán/administración & dosificación , Losartán/antagonistas & inhibidores , Masculino , Radioinmunoensayo , Ratas , Ratas Sprague-DawleyRESUMEN
Cardiovascular responses to central losartan (LOS), a non-peptide angiotensin II (ANG II) receptor antagonist, were investigated by comparing the effects of LOS injection into the 3rd and 4th cerebral ventricles (3rdV, 4thV) on mean arterial pressure (MAP) and heart rate (HR). Adult male Holtzman rats were used (N = 6 animals per group). Average basal MAP and HR were 114 +/- 3 mmHg and 343 +/- 9 bpm (N = 23), respectively. LOS (50, 100 or 200 nmol/2 microliters) injected into the 3rdV induced pressor (peak of 25 +/- 3 mmHg) and tachycardic (peak of 60 +/- 25 bpm) responses. LOS injected into the 4thV had no effect on MAP, but it induced bradycardia (peak of -35 +/- 15 bpm). KCl (200 nmol/2 microliters) injected into the 3rdV or into the 4thV had no effect on either MAP or HR compared to 0.9% saline injection. The results indicate that LOS injected into the third ventricle acts on forebrain structures to induce its pressor and tachycardic effects and that bradycardia, likely dependent on hindbrain structures, is obtained when LOS is injected into the fourth ventricle.
Asunto(s)
Compuestos de Bifenilo/farmacología , Presión Sanguínea/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Imidazoles/farmacología , Tetrazoles/farmacología , Análisis de Varianza , Animales , Compuestos de Bifenilo/administración & dosificación , Imidazoles/administración & dosificación , Inyecciones Intraventriculares , Losartán , Masculino , Ratas , Ratas Sprague-Dawley , Tetrazoles/administración & dosificaciónRESUMEN
Natriuresis, kaliuresis, diuresis, arterial pressure and heart rate were studied in rats following dehydration and cholinergic stimulation of the medial septal area (MSA). The increase in renal Na+ and K+ excretion produced by the injection of carbachol (2 nmol) into the MSA in normal hydrated rats was abolished in 48-h water-deprived rats. Urinary volume was also reduced. Cholinergic stimulation of the MSA produced a smaller increase in arterial pressure in 48-h water-deprived rats compared to normal hydrated animals. No change was observed in heart rate. These results show that hydration state is essential for the central cholinergic control of electrolyte excretion and increase in arterial pressure.
Asunto(s)
Presión Sanguínea/fisiología , Deshidratación/fisiopatología , Riñón/fisiología , Núcleos Septales/fisiología , Animales , Carbacol , Diuresis/efectos de los fármacos , Riñón/metabolismo , Masculino , Potasio/metabolismo , Ratas , Ratas Endogámicas , Sodio/metabolismoRESUMEN
It is not known whether the addition of ezetimibe to statins adds cardiovascular protection beyond the expected changes in lipid levels. Subjects with coronary heart disease were treated with four consecutive 1-week courses of therapy (T) and evaluations. The courses were: T1, 100 mg aspirin alone; T2, 100 mg aspirin and 40 mg simvastatin/10 mg ezetimibe; T3, 40 mg simvastatin/10 mg ezetimibe, and 75 mg clopidogrel (300 mg initial loading dose); T4, 75 mg clopidogrel alone. Platelet aggregation was examined in whole blood. Endothelial microparticles (CD51), platelet microparticles (CD42/CD31), and endothelial progenitor cells (CD34/CD133; CDKDR/CD133, or CD34/KDR) were quantified by flow cytometry. Endothelial function was examined by flow-mediated dilation. Comparisons between therapies revealed differences in lipids (T2 and T3Asunto(s)
Azetidinas/farmacología
, Micropartículas Derivadas de Células/efectos de los fármacos
, Enfermedad Coronaria/tratamiento farmacológico
, Células Progenitoras Endoteliales/efectos de los fármacos
, Agregación Plaquetaria/efectos de los fármacos
, Simvastatina/farmacología
, Anciano
, Anticolesterolemiantes/farmacología
, Aspirina/uso terapéutico
, LDL-Colesterol/sangre
, Clopidogrel
, Combinación de Medicamentos
, Ezetimiba
, Femenino
, Citometría de Flujo
, Humanos
, Masculino
, Persona de Mediana Edad
, Inhibidores de Agregación Plaquetaria/uso terapéutico
, Ticlopidina/análogos & derivados
, Ticlopidina/uso terapéutico
, Triglicéridos/sangre
RESUMEN
The blockade of serotoninergic receptors with methysergide or the activation of alpha(2)-adrenoceptors with moxonidine into the lateral parabrachial nucleus (LPBN) increases water and 0.3 M NaCl intake in rats treated with furosemide (FURO) combined with captopril (CAP). In the present study we investigated the effects of bilateral injections of noradrenaline (the endogenous neurotransmitter for alpha-adrenoceptors) alone or combined with the alpha(2)-adrenoceptor antagonist RX 821002 into the LPBN or into the rostral portion of the Kölliker-Fuse nucleus that includes also the A7 area (KF/A7 area) on FURO+CAP-induced water and 0.3 M NaCl intake. Male Holtzman rats with bilateral stainless steel guide-cannulas implanted into KF/A7 area or LPBN were used. FURO+CAP-induced 0.3 M NaCl intake strongly increased after bilateral injections of noradrenaline (80 or 160 nmol/0.2 microl) into LPBN (26.5+/-5.9 and 20.7+/-2.0 ml/2 h versus saline: 4.4+/-0.9 ml/2 h) or into the KF/A7 area (31.5+/-6.1 and 25.9+/-4.7 ml/2 h versus saline: 7.2+/-1.6 ml/2 h). Water intake increased with noradrenaline injected in KF/A7 area, however, this treatment reduced 0.06 M sucrose intake, suggesting that the increase of water and NaCl intake is not related to non-specific effect. Bilateral injections of RX 821002 (160 nmol/0.2 microl) into LPBN or KF/A7 area abolished the effects of noradrenaline (160 nmol/0.2 microl) in the same areas on 0.3 M NaCl intake (7.5+/-2.5 and 9.8+/-4.4 ml/2 h, respectively). Moxonidine (0.5 nmol/0.2 microl) injected bilaterally into the KF/A7 area increased 0.3 M NaCl intake (39.5+/-6.3 ml/3 h) and water intake, while methysergide (4 microg/0.2 microl) into the KF/A7 area did not alter 0.3 M NaCl or water intake. The results suggest that alpha(2)-adrenoceptor activation is a common mechanism in the KF/A7 area and LPBN to facilitate sodium intake. However, the serotonergic mechanism is present in LPBN, not in the KF/A7 area.
Asunto(s)
Adrenérgicos/farmacología , Conducta de Ingestión de Líquido/efectos de los fármacos , Puente/efectos de los fármacos , Cloruro de Sodio Dietético , Agua , Agonistas alfa-Adrenérgicos/farmacología , Antagonistas Adrenérgicos alfa/farmacología , Animales , Captopril/farmacología , Sacarosa en la Dieta , Conducta de Ingestión de Líquido/fisiología , Furosemida/farmacología , Idazoxan/análogos & derivados , Idazoxan/farmacología , Masculino , Natriuréticos/farmacología , Norepinefrina/farmacología , Puente/fisiología , Ratas , Ratas Sprague-DawleyRESUMEN
It is not known whether the addition of ezetimibe to statins adds cardiovascular protection beyond the expected changes in lipid levels. Subjects with coronary heart disease were treated with four consecutive 1-week courses of therapy (T) and evaluations. The courses were: T1, 100 mg aspirin alone; T2, 100 mg aspirin and 40 mg simvastatin/10 mg ezetimibe; T3, 40 mg simvastatin/10 mg ezetimibe, and 75 mg clopidogrel (300 mg initial loading dose); T4, 75 mg clopidogrel alone. Platelet aggregation was examined in whole blood. Endothelial microparticles (CD51), platelet microparticles (CD42/CD31), and endothelial progenitor cells (CD34/CD133; CDKDR/CD133, or CD34/KDR) were quantified by flow cytometry. Endothelial function was examined by flow-mediated dilation. Comparisons between therapies revealed differences in lipids (T2 and T3<T1 and T4 for total cholesterol, LDL-C, and triglycerides; P<0.002 for all), as well as for endothelial function (T2>T1 and T4, P=0.001). Decreased platelet aggregation was observed after aspirin (arachidonic acid, T1<T3 and T4, P=0.034) and clopidogrel (adenosine, T3 and T4<T1 and T2, P<0.0001) therapy. Simvastatin/ezetimibe diphosphate did not change platelet aggregation, the amount of circulating endothelial and platelet microparticles, or endothelial progenitor cells. Cardiovascular protection following therapy with simvastatin/ezetimibe seems restricted to lipid changes and improvement of endothelial function not affecting the release of microparticles, mobilization of endothelial progenitor cells or decreased platelet aggregation.
Asunto(s)
Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Azetidinas/farmacología , Micropartículas Derivadas de Células/efectos de los fármacos , Enfermedad Coronaria/tratamiento farmacológico , Células Progenitoras Endoteliales/efectos de los fármacos , Agregación Plaquetaria/efectos de los fármacos , Simvastatina/farmacología , Anticolesterolemiantes/farmacología , Aspirina/uso terapéutico , LDL-Colesterol/sangre , Combinación de Medicamentos , Citometría de Flujo , Inhibidores de Agregación Plaquetaria/uso terapéutico , Ticlopidina/análogos & derivados , Ticlopidina/uso terapéutico , Triglicéridos/sangreRESUMEN
Losartan, an AT1 angiotensin II (ANG II) receptor non-peptide antagonist, induces an increase in mean arterial pressure (MAP) when injected intracerebroventricularly (icv) into rats. The present study investigated possible effector mechanisms of the increase in MAP induced by icv losartan in unanesthetized rats. Male Holtzman rats (280-300 g, N = 6/group) with a cannula implanted into the anterior ventral third ventricle received an icv injection of losartan (90 æg/2 æl) that induced a typical peak pressor response within 5 min. In one group of animals, this response to icv losartan was completely reduced from 18 ± 1 to 4 ± 2 mmHg by intravenous (iv) injection of losartan (2.5-10 mg/kg), and in another group, it was partially reduced from 18 ± 3 to 11 ± 2 mmHg by iv prazosin (0.1-1.0 mg/kg), an alpha1-adrenergic antagonist (P<0.05). Captopril (10 mg/kg), a converting enzyme inhibitor, injected iv in a third group inhibited the pressor response to icv losartan from 24 ± 3 to 7 ± 2 mmHg (P<0.05). Propranolol (10 mg/kg), a ß-adrenoceptor antagonist, injected iv in a fourth group did not alter the pressor response to icv losartan. Plasma renin activity and serum angiotensin-converting enzyme activity were not altered by icv losartan in other animals. The results suggest that the pressor effect of icv losartan depends on angiotensinergic and alpha1-adrenoceptor activation, but not on increased circulating ANG II
Asunto(s)
Animales , Masculino , Ratas , Agonistas alfa-Adrenérgicos , Inhibidores de la Enzima Convertidora de Angiotensina , Hipertensión , Losartán , Peptidil-Dipeptidasa A , Receptores de Angiotensina , Renina , Captopril , Inyecciones Intraventriculares , Losartán , Prazosina , Propranolol , Radioinmunoensayo , Ratas Sprague-DawleyRESUMEN
Carciovascular responses to central losartan (LOS), a non-peptide angiotensin II (ANG II) receptor antagonist, were investigated by comparing the effects of LOS injection into the 3rd and 4th cerebral ventricles (3rdV, 4thV) on mean arterial pressure (MAP) and heart rate (HR). Adult male Holtzman rats were used (N = 6 animals per group). Average basal MAP and HR were 114 + or - 3 mmHg and 343 + or - 9 bpm (N = 23), respectively. LOS (50, 100 or 200 nmol/2 µl) injected into the 3rdV induced pressor (peak of 25 + or - 3 mmHg) and tachycardic (peak of 60 + or - 25 bpm) responses. LOS injected into the 4thV had no effect on MAP, but it induced bradycardia (peak of -35 + or - 15 bpm). KCl (200 nmol/2 µl) injected into the 3rdV or into the 4thV had no effect on either MAP or HR compared to 0.9 percent saline injection. The results indicate that LOS injected into the third ventricle acts on forebrain structures to induce its pressor and tachycardic effects and that bradycardia, likely dependent on hindbrain structures, is obtained when LOS is injected into the fourth ventricle
Asunto(s)
Animales , Masculino , Ratas , Frecuencia Cardíaca , Imidazoles/farmacología , Presión Arterial , Análisis de Varianza , Imidazoles/administración & dosificación , Inyecciones Intraventriculares , Ratas Sprague-DawleyRESUMEN
Natriuresis, kaliuresis, diuresis, arterial pressure and heart rate were studied in rats following dehydration and cholinergic stimulation of the medial septal area (MSA). The increase in renal NA+ and K+ excretion produced by the injection of carbachol (2nmol) into the MSA in normal hydrated rats was abolished in 48-h water-deprived rats. Urinary volume was also reduced. Cholinergic stimulation of the MSA produced a smaller mincrease in arterial pressure in 48-h-deprived rats compared to normal hydrated animals. No change was observed in heart rate. These reults show that hydration state is essential for the central cholinergic control of electrolyte excretion and increase in arterial pressure