Smell loss associated with SARS-CoV-2 is not clinically different from other viruses: a multicenter cohort study.

BACKGROUND: Although the COVID-19 pandemic has increased the prevalence of cases with olfactory loss, other respiratory viruses can also cause this condition. We aimed to compare the prevalence of acute SARS-CoV-2 infection and other respiratory viruses in patients with sudden smell loss, and to assess the impact of SARS-CoV-2 viral load and co-infection on olfactory symptoms. METHODS: Patients with sudden smell loss were recruited in a multicenter prospective cohort study in 15 hospitals in Brazil. Clinical questionnaire, Connecticut Chemosensory Clinical Research Center (CCCRC) olfactory test and nasopharyngeal swab to perform a PCR-based respiratory viral panel were collected at first visit (day 0) and 30 and 60 days after recruitment. RESULTS: 188 of 213 patients presented positive test result for SARS-CoV-2, among which 65 were co-infected with other respiratory viruses (e.g., rhinovirus, enterovirus, and parainfluenza). 25 had negative test results for SARS-CoV-2. Patients in both SARSCoV-2 and non-SARS-CoV-2 groups had objective anosmia (less than 2 points according to the psychophysical olfactory CCCRC) at day 0, with no significant difference between them. Both groups had significant smell scores improvement after 30 and 60 days, with no difference between them. Co-infection with other respiratory viruses, and SARS-CoV-2 viral load did not impact olfactory scores. CONCLUSION: Patients with sudden smell loss associated with SARS-CoV-2 and other respiratory viruses had similar presentation, with most participants initiating with anosmia, and total or near total recovery after 60 days. SARS-CoV-2 viral load and co-infections with other respiratory viruses were not associated with poorer olfactory outcomes.

[Validity and reliability of the QOLIE-10 instrument for assessing health related quality of life in epilepsy of refractory epilepsy adult patients at a Colombian neurological center]. / Validez y fiabilidad del instrumento para evaluación de calidad de vida relacionada con la salud en epilepsia QOLIE-10 en pacientes adultos con epilepsia refractaria en un centro neurológico colombiano.

AIM: To determine feasibility, reliability and validity of the shortened version of the Quality of Life in Epilepsy Inventory-10 (QOLIE-10) in a population of refractory epilepsy adult patients in the Colombian Caribbean. PATIENTS AND METHODS: Data were collected from 63 adult refractory epilepsy patients. The ten items of QOLIE-10 were derived from the Spanish version of QOLIE-89. We assess feasibility, validity, factorial analysis with communalities, reliability through internal consistency and sensitivity to change. RESULTS: Clinical and demographic features were determined; quality of life was established through frequencies. Construct validity: through factor analysis communalities there were no items considered irrelevant and were grouped into one single dimension. Kaiser-Meyer-Olkin: 0.891. Bartlett's test of sphericity: p < 0.001. Average intraclass correlation coefficient 0.843. The internal consistency reliability coefficient (Cronbach's alpha) was 0.98. The QOLIE-10 questionnaire for the assessment of health-related quality of life was validated in Spanish for adult patients with refractory epilepsy with excellent validity, reliability parameters and easy, quick filling. CONCLUSIONS: The QOLIE-10 questionnaire is a valid and reliable tool for use in adult patients with refractory epilepsy in Colombia. Health professionals are encouraged to use this questionnaire to routinely examine the influences of the disease process in epilepsy patients.

TITLE: Validez y fiabilidad del instrumento para evaluación de calidad de vida relacionada con la salud en epilepsia QOLIE-10 en pacientes adultos con epilepsia refractaria en un centro neurológico colombiano.Objetivo. Determinar la factibilidad, la fiabilidad y la validez de la versión en castellano del cuestionario breve de calidad de vida relacionada con la salud en epilepsia QOLIE-10 en una población de pacientes adultos con epilepsia refractaria de un centro de referencia de enfermedades neurológicas del Caribe colombiano. Pacientes y métodos. Se recogieron datos de 63 pacientes con epilepsia refractaria. Los 10 ítems del cuestionario QOLIE-10 se derivaron de la versión en castellano del cuestionario QOLIE-89. Se evaluó la factibilidad, la validez, el análisis factorial con comunalidades, la fiabilidad a través de la consistencia interna y la sensibilidad al cambio. Resultados. Se determinaron las características demográficas y clínicas, y se determinó la calidad de vida por medio de las frecuencias. Validez de constructo: análisis factorial y comunalidades, no se encontraron ítems no relevantes y se agruparon en una sola dimensión. Kaiser-Meyer-Olkin: 0,891. Esfericidad de Barlett: p menos de 0,001. Coeficiente de correlación intraclase media: 0,843. Fiabilidad: consistencia interna alfa de Cronbach, 0,98. Se validó el cuestionario QOLIE-10 de calidad de vida relacionada con la salud en adultos con epilepsia refractaria en castellano, con excelentes parámetros de fiabilidad y validez, y una administración rápida y fácil. Conclusiones. El cuestionario QOLIE-10 se considera una herramienta válida y fiable para su uso en la población de pacientes con epilepsia refractaria en Colombia. Se alienta a los profesionales de la salud a usar este cuestionario para examinar de manera rutinaria la influencia del proceso de enfermedad en la calidad de vida de los pacientes con epilepsia.

Medial septal area vasopressin receptor subtypes in the regulation of urine and sodium excretion in rats.

The present study aimed to determine the effects of selective antagonists of V(1a), V(2), and V(1a)/V(2) (Conivaptan; Astellas Pharma Inc., Tokyo, Japan) arginine vasopressin (AVP) receptors on the flow of urine and sodium excretion induced by AVP, by means of microinjections into the medial septal area (MSA) of the rat brain. Male Holtzman rats had a guide cannula implanted into the dorsal surface of the MSA. Intravenous infusion of hypotonic saline was used to promote urinary flow, which was collected for 4 h. Pretreatment with the V(1a) antagonist decreased, and the V(2) antagonist and Conivaptan (a V(1a)/V(2) antagonist) increased, the urinary flow induced by AVP. Administration of AVP increased sodium excretion. Pretreatment with V(2) or V(1a) antagonists decreased, and Conivaptan abolished, the sodium excretion induced by AVP. These results indicate that the V(1a) and V(2) receptors of the MSA are important in the central regulation of urine and sodium excretion.

Effects of angiotensin and vasopressin V(1) receptors on water and sodium intake induced by injection of vasopressin into lateral septal area.

The specific arginine(8)-vasopressin (AVP) V(1) receptors antagonist (AAVP) was injected (20, 40 and 80 nmol) into the lateral septal area (LSA) to determine the effects of selective septal V(1) receptor on water and 3% sodium intake in rats. Was also observed the effects of losartan and CGP42112A (select ligands of the AT(1) and AT(2) ANG II receptors, respectively) injected into LSA prior AVP on the same appetites. Twenty-four hours before the experiments, the rats were deprived of water. The volume of drug solution injected was 0.5 microl. Water and sodium intake were measured at 0.25, 0.5, 1.0 and 2.0 h. Injection of AVP reduced the water and sodium ingestion vs. control (0.15 M saline). Pre-treatment with AAVP (40, 80 and 160 nmol) did not alter the decrease in the water ingestion induced by AVP, whereas AAVP abolished the action of AVP-induced sodium intake. Losartan (40, 80 and 160 nmol) did not alter the effect of AVP on water and sodium intake, whereas CGP42112A (20, 40 and 60 nmol) at the first 30 min increased water ingestion. Losartan and CGP42112A together increased the actions of AVP, showing more pronounced effects than when the two antagonists were injected alone. The results showed that AVP inhibited the appetites and these effects were increased by the AAVP. The involvement of angiotensinergic receptors in the effects of AVP is also suggested.

Role of nitric oxide of the median preoptic nucleus (MnPO) in the alterations of salivary flow, arterial pressure and heart rate induced by injection of pilocarpine into the MnPO and intraperitoneally.

We investigated the effect of L-NAME, a nitric oxide (NO) inhibitor and sodium nitroprusside (SNP), an NO-donating agent, on pilocarpine-induced alterations in salivary flow, mean arterial blood pressure (MAP) and heart rate (HR) in rats. Male Holtzman rats (250-300 g) were implanted with a stainless steel cannula directly into the median preoptic nucleus (MnPO). Pilocarpine (10, 20, 40, 80, 160 g) injected into the MnPO induced an increase in salivary secretion (P<0.01). Pilocarpine (1, 2, 4, 8, 16 mg/kg) ip also increased salivary secretion (P<0.01). Injection of L-NAME (40 g) into the MnPO prior to pilocarpine (10, 20, 40, 80, 160 g) injected into the MnPO or ip (1, 2, 4, 8, 16 mg/kg) increased salivary secretion (P<0.01). SNP (30 g) injected into the MnPO or ip prior to pilocarpine attenuated salivary secretion (P<0.01). Pilocarpine (40 g) injection into the MnPO increased MAP and decreased HR (P<0.01). Pilocarpine (4 mg/kg body weight) ip produced a decrease in MAP and an increase in HR (P<0.01). Injection of L-NAME (40 g) into the MnPO prior to pilocarpine potentiated the increase in MAP and reduced HR (P<0.01). SNP (30 g) injected into the MnPO prior to pilocarpine attenuated (100%) the effect of pilocarpine on MAP, with no effect on HR. Administration of L-NAME (40 g) into the MnPO potentiated the effect of pilocarpine injected ip. SNP (30 g) injected into the MnPO attenuated the effect of ip pilocarpine on MAP and HR. The present study suggests that in the rat MnPO 1) NO is important for the effects of pilocarpine on salivary flow, and 2) pilocarpine interferes with blood pressure and HR (side effects of pilocarpine), that is attenuated by NO.

Role of nitric oxide of the median preoptic nucleus (MnPO) in the alterations of salivary flow, arterial pressure and heart rate induced by injection of pilocarpine into the MnPO and intraperitoneally

We investigated the effect of L-NAME, a nitric oxide (NO) inhibitor and sodium nitroprusside (SNP), an NO-donating agent, on pilocarpine-induced alterations in salivary flow, mean arterial blood pressure (MAP) and heart rate (HR) in rats. Male Holtzman rats (250-300 g) were implanted with a stainless steel cannula directly into the median preoptic nucleus (MnPO). Pilocarpine (10, 20, 40, 80, 160 æg) injected into the MnPO induced an increase in salivary secretion (P<0.01). Pilocarpine (1, 2, 4, 8, 16 mg/kg) ip also increased salivary secretion (P<0.01). Injection of L-NAME (40 æg) into the MnPO prior to pilocarpine (10, 20, 40, 80, 160 æg) injected into the MnPO or ip (1, 2, 4, 8, 16 mg/kg) increased salivary secretion (P<0.01). SNP (30 æg) injected into the MnPO or ip prior to pilocarpine attenuated salivary secretion (P<0.01). Pilocarpine (40 æg) injection into the MnPO increased MAP and decreased HR (P<0.01). Pilocarpine (4 mg/kg body weight) ip produced a decrease in MAP and an increase in HR (P<0.01). Injection of L-NAME (40 æg) into the MnPO prior to pilocarpine potentiated the increase in MAP and reduced HR (P<0.01). SNP (30 æg) injected into the MnPO prior to pilocarpine attenuated (100 percent) the effect of pilocarpine on MAP, with no effect on HR. Administration of L-NAME (40 æg) into the MnPO potentiated the effect of pilocarpine injected ip. SNP (30 æg) injected into the MnPO attenuated the effect of ip pilocarpine on MAP and HR. The present study suggests that in the rat MnPO 1) NO is important for the effects of pilocarpine on salivary flow, and 2) pilocarpine interferes with blood pressure and HR (side effects of pilocarpine), that is attenuated by NO

The EBV action in tonsils and adenoids.

The bacteria involved in tonsil disease have been well studied, but we cannot say the same for the viruses. The method to detect virus make this approach difficult to study. Epstein-Barr Virus (EBV) infection usually occurs in early childhood and can persist in palatine and pharyngeal tonsil lymphocytes. EBV has been closely associated with the undifferentiated form of nasopharyngeal carcinoma (NPC) in its effect. Nevertheless, the presence of EBV in non-neoplastic lymphoid tissue of the nasopharynx and tonsil has rarely been investigated. Our objective was to study the frequency of EBV in tonsils and adenoids and to define the correlation between EBV and adenoid hyperplasia. In this study, we looked for EBV in adenoid and tonsil tissue of 165 patients (2 and 15 years old ) by in situ hybridization (ISH) for EBER 1/2 RNA. Resection of the adenoids was done for relief of upper respiratory tract obstruction, and the tonsils were resected because of recurrent tonsillitis and/or hyperplasia with upper airway obstruction. We divided the adenoid samples in two groups: one group 12-24 months old (average 18 months old) and the second group, 25 months to 15 years old. Tonsils were obtained from 85 patients, 3-13 years old (mean age 5.6 years) who underwent surgery due to recurrent tonsillitis or hyperplasia. EBV was demonstrated in lymphoid cells of 11 (34.3%) out of 32 adenoids for the first group and 36 (72%) out of 48 children of the second group. EBV was found in the respiratory epithelial cells of adenoid in one case. Children under 24 months of age can be infected by EBV, and this virus might be responsible for obstructive hyperplasia. Tonsils are less affected by EBV than the adenoids, suggesting that the EBV is more attracted to the adenoid tissue than the tonsillar tissue.

Interaction between paraventricular nucleus and septal area in the control of physiological responses induced by angiotensin II.

We determined the effects of losartan (40 nmol) and PD 123319 (40 nmol) (both non-peptides and selective antagonists of the AT1 and AT2 angiotensin receptors, respectively), and [Sar1, Ala8] angiotensin II (ANG II) (40 nmol) (a non-selective peptide antagonist of angiotensin receptors) injected into the paraventricular nucleus (PVN) on the water and salt appetite, diuresis and natriuresis and mean arterial pressure (MAP) induced by administration of 10 nmol of ANG II into the medial septal area (MSA) of male Holtzman rats weighing 250-300 g. The volume of drug solution injected was 0.5 micro l over a period of 10-15 s. The responses were measured over a period of 120 min. ANG II alone injected into the MSA induced an increase in all the above parameters (8.1 +/- 1.2, 1.8 +/- 0.3, and 17.1 +/- 1.0 ml, 217 +/- 25 micro Eq/120 min, and 24 +/- 4 mmHg, respectively, N = 10-12) compared with vehicle-treated rats (1.4 +/- 0.2, 0.6 +/- 0.1, and 9.3 +/- 0.5 ml, 47 +/- 5 micro Eq/120 min, and 4.1 +/- 0.8 mmHg, respectively, N = 10-14). Pretreatment with losartan and [Sar1, Ala8] ANG II completely abolished the water and sodium intake, and the pressor increase (0.5 +/- 0.2, 1.1 +/- 0.2, 0.5 +/- 0.2, and 0.8 +/- 0.2 ml, and 1.2 +/- 3.9, 31 +/- 4.6 mmHg, respectively, N = 9-12), whereas losartan blunted the urinary and sodium excretion induced by ANG II (13.9 +/- 1.0 ml and 187 +/- 10 micro Eq/120 min, respectively, N = 9). Pretreatment with PD 123319 and [Sar1, Ala8] ANG II blocked the urinary and sodium excretion (10.7 +/- 0.8, 9.8 +/- 0.7 ml, and 67 +/- 13 and 57 +/- 17 micro Eq/120 min, respectively, N = 9), whereas pretreatment with PD 123319 partially blocked the water and sodium intake, and the MAP induced by ANG II administration (2.3 +/- 0.3, 1.1 +/- 0.1 ml, and 12 +/- 3 mmHg, respectively, N = 9-10). These results suggest the angiotensinergic effect of the MSA on the AT1 and AT2 receptors of the PVN in terms of water and sodium homeostasis and MAP modulation.

Interaction between paraventricular nucleus and septal area in the control of physiological responses induced by angiotensin II

We determined the effects of losartan (40 nmol) and PD 123319 (40 nmol) (both non-peptides and selective antagonists of the AT1 and AT2 angiotensin receptors, respectively), and [Sar¹, Ala8] angiotensin II (ANG II) (40 nmol) (a non-selective peptide antagonist of angiotensin receptors) injected into the paraventricular nucleus (PVN) on the water and salt appetite, diuresis and natriuresis and mean arterial pressure (MAP) induced by administration of 10 nmol of ANG II into the medial septal area (MSA) of male Holtzman rats weighing 250-300 g. The volume of drug solution injected was 0.5 æl over a period of 10-15 s. The responses were measured over a period of 120 min. ANG II alone injected into the MSA induced an increase in all the above parameters (8.1 ± 1.2, 1.8 ± 0.3, and 17.1 ± 1.0 ml, 217 ± 25 æEq/120 min, and 24 ± 4 mmHg, respectively, N = 10-12) compared with vehicle-treated rats (1.4 ± 0.2, 0.6 ± 0.1, and 9.3 ± 0.5 ml, 47 ± 5 æEq/120 min, and 4.1 ± 0.8 mmHg, respectively, N = 10-14). Pretreatment with losartan and [Sar¹, Ala8] ANG II completely abolished the water and sodium intake, and the pressor increase (0.5 ± 0.2, 1.1 ± 0.2, 0.5 ± 0.2, and 0.8 ± 0.2 ml, and 1.2 ± 3.9, 31 ± 4.6 mmHg, respectively, N = 9-12), whereas losartan blunted the urinary and sodium excretion induced by ANG II (13.9 ± 1.0 ml and 187 ± 10 æEq/120 min, respectively, N = 9). Pretreatment with PD 123319 and [Sar¹, Ala8] ANG II blocked the urinary and sodium excretion (10.7 ± 0.8, 9.8 ± 0.7 ml, and 67 ± 13 and 57 ± 17 æEq/120 min, respectively, N = 9), whereas pretreatment with PD 123319 partially blocked the water and sodium intake, and the MAP induced by ANG II administration (2.3 ± 0.3, 1.1 ± 0.1 ml, and 12 ± 3 mmHg, respectively, N = 9-10). These results suggest the angiotensinergic effect of the MSA on the AT1 and AT2 receptors of the PVN in terms of water and sodium homeostasis and MAP modulation

Adrenoceptors of the medial septal area modulate water intake and renal excretory function induced by central administration of angiotensin II.

We investigated the role of alpha-adrenergic antagonists and clonidine injected into the medial septal area (MSA) on water intake and the decrease in Na+, K+ and urine elicited by ANGII injection into the third ventricle (3rdV). Male Holtzman rats with stainless steel cannulas implanted into the 3rdV and MSA were used. ANGII (12 nmol/ micro l) increased water intake (12.5 +/- 1.7 ml/120 min). Clonidine (20 nmol/ micro l) injected into the MSA reduced the ANGII-induced water intake (2.9 +/- 0.5 ml/120 min). Pretreatment with 80 nmol/ micro l yohimbine or prazosin into the MSA also reduced the ANGII-induced water intake (3.0 +/- 0.4 and 3.1 +/- 0.2 ml/120 min, respectively). Yohimbine + prazosin + clonidine injected into the MSA abolished the ANGII-induced water intake (0.2 +/- 0.1 and 0.2 +/- 0.1 ml/120 min, respectively). ANGII reduced Na+ (23 +/- 7 micro Eq/120 min), K+ (27 +/- 3 micro Eq/120 min) and urine volume (4.3 +/- 0.9 ml/120 min). Clonidine increased the parameters above. Clonidine injected into the MSA abolished the inhibitory effect of ANGII on urinary sodium. Yohimbine injected into the MSA also abolished the inhibitory effects of ANGII. Yohimbine + clonidine attenuated the inhibitory effects of ANGII. Prazosin injected into the MSA did not cause changes in ANGII responses. Prazosin + clonidine attenuated the inhibitory effects of ANGII. The results showed that MSA injections of alpha1- and alpha2-antagonists decreased ANGII-induced water intake, and abolished the Na+, K+ and urine decrease induced by ANGII into the 3rdV. These findings suggest the involvement of septal alpha1- and alpha2-adrenergic receptors in water intake and electrolyte and urine excretion induced by central ANGII.

Adrenoceptors of the medial septal area modulate water intake and renal excretory function induced by central administration of angiotensin II

We investigated the role of alpha-adrenergic antagonists and clonidine injected into the medial septal area (MSA) on water intake and the decrease in Na+, K+ and urine elicited by ANGII injection into the third ventricle (3rdV). Male Holtzman rats with stainless steel cannulas implanted into the 3rdV and MSA were used. ANGII (12 nmol/æl) increased water intake (12.5 ± 1.7 ml/120 min). Clonidine (20 nmol/æl) injected into the MSA reduced the ANGII-induced water intake (2.9 ± 0.5 ml/120 min). Pretreatment with 80 nmol/æl yohimbine or prazosin into the MSA also reduced the ANGII-induced water intake (3.0 ± 0.4 and 3.1 ± 0.2 ml/120 min, respectively). Yohimbine + prazosin + clonidine injected into the MSA abolished the ANGII-induced water intake (0.2 ± 0.1 and 0.2 ± 0.1 ml/120 min, respectively). ANGII reduced Na+ (23 ± 7 æEq/120 min), K+ (27 ± 3 æEq/120 min) and urine volume (4.3 ± 0.9 ml/120 min). Clonidine increased the parameters above. Clonidine injected into the MSA abolished the inhibitory effect of ANGII on urinary sodium. Yohimbine injected into the MSA also abolished the inhibitory effects of ANGII. Yohimbine + clonidine attenuated the inhibitory effects of ANGII. Prazosin injected into the MSA did not cause changes in ANGII responses. Prazosin + clonidine attenuated the inhibitory effects of ANGII. The results showed that MSA injections of alpha1- and alpha2-antagonists decreased ANGII-induced water intake, and abolished the Na+, K+ and urine decrease induced by ANGII into the 3rdV. These findings suggest the involvement of septal alpha1- and alpha2-adrenergic receptors in water intake and electrolyte and urine excretion induced by central ANGII

Avaliaçäo auditiva em escolares / Hearing evaluation of school children

Introduçäo: A avaliaçäo auditiva na faixa etária escolar é necessária para a identificaçäo e correçäo precoce das alteraçöes auditivas. Objetivos: Identificar e quantificar as alteraçöes audiométricas mais freqüentes em escolares. Casuística e Método: Pesquisa realizada com 121 escolares da 1ª a 8ª séries, faixa etária de 7 a 14 anos no mês de novembro de 1998 na cidade de Goiânia, por médicos otorrinolaringologistas e fonoaudiólogos através de exame clínico otorrinolaringológico, audiometria tonal e imitânciometria no Ambulatório de Otorrinolaringologia do Hospital das Clínicas da Faculdade de Medicina da Universidade Federal de Goiás. Resultados: Audiometrias realizadas em 242 orelhas foram encontradas: 76 por cento (184) orelhas com audiometria dentro dos limites da normalidade e 24 por cento (58) orelhas com audiometria alterada. As alteraçöes audiométricas mais freqüentes foram: perda auditiva condutiva em 12 por cento (26) sendo 8 por cento (16) esquerdas e 4 por cento (9) direitas, perda auditiva neurossensorial leve em 7 por cento (15) orelhas sendo 2 por cento (5) esquerdas e 5 por cento (10) direitas. Imitânciometria realizada em 242 orelhas obtendo timpanometrias alteradas sendo: curva do tipo B 3 por cento (6) e do tipo C 3 por cento (6). Conclusäo: Concluímos que as alteraçöes auditivas que ocorrem podem prejudicar a atençäo e compreensäo dos escolares, sendo importante o seu diagnóstico e tratamento precoce para obtençäo de um melhor rendimento escolar

Role of the alpha(1)- and alpha(2)-adrenoceptors of the paraventricular nucleus on the water and salt intake, renal excretion, and arterial pressure induced by angiotensin II injection into the medial septal area.

In this study we investigated the influence of alpha-adrenergic antagonists injections into the paraventricular nucleus (PVN) of the hypothalamus on the thirst and salt appetite, diuresis, natriuresis, and pressor effects of angiotensin II (ANG II) stimulation of medial septal area (MSA). ANG II injection into the MSA induced water and sodium intake, diuresis, natriuresis, and pressor responses. The previous injection of prazosin (an alpha(1)-adrenergic antagonist) into the PVN abolished, whereas previous administration of yohimbine (an alpha(2)-adrenergic antagonist) into the PVN increased the water and sodium intake, urinary, natriuretic, and pressor responses induced by ANG II injected into the MSA. Previous injection of a nonselective alpha-adrenergic antagonist, regitin, into the PVN blocked the urinary excretion, and reduced the water and sodium intake, sodium intake, and pressor responses induced by ANG II injected into the MSA. The present results suggest that alpha-adrenergic pathways involving the PVN are important for the water and sodium excretion, urine and sodium excretion, and pressor responses, induced by angiotensinergic activation of the MSA.

Effects of subtypes alpha- and beta-adrenoceptors of the lateral hypothalamus on the water and sodium intake induced by angiotensin II injected into the subfornical organ.

The present experiments were conducted to investigate the role of the alpha(1A)-, alpha(1B), beta(1)- and beta(2)-adrenoceptors of the lateral hypothalamus (LH) on the water and salt intake responses elicited by subfornical organ (SFO) injection of angiotensin II (ANG II) in rats. 5-methylurapidil (an alpha(1A)-adrenergic antagonist), cyclazosin (an alpha(1B)-adrenergic antagonist) and ICI-118,551 (a beta(2)-adrenergic antagonist) injected into the LH produced a dose-dependent reduction, whereas efaroxan (an alpha(2)-antagonist) increased the water intake induced by administration of ANG II into the SFO. These data show that injection of 5-methylurapidil into the LH prior to ANG II into the SFO increased the water and sodium intake induced by the injection of ANG II. The present data also show that atenolol (a beta(1)-adrenergic antagonist), ICI-118,551, cyclazosin, or efaroxan injected into the LH reduced in a dose-dependent manner the water and sodium intake to angiotensinergic activation of SFO. Thus, the alpha(1)- and beta-adrenoceptors of the LH are possibly involved with central mechanisms dependent on ANG II and SFO that control water and sodium intake.

Participation of alpha-1 and alpha-2 adrenoceptors of the lateral hypothalamic area in water intake, and renal sodium, potassium and urinary volume excretion induced by central administration of angiotensin II.

The circumventricular structures and the lateral hypothalamus (LH) have been shown to be important for the central action of angiotensin II (ANGII) on water and electrolyte regulation. Several anatomical findings have demonstrated neural connection between circumventricular structures and the LH. The present experiments were conducted to investigate the role of the alpha-adrenergic antagonists and agonistic injected into the LH on the water intake, sodium and potassium excretion elicited by injections of ANGII into the lateral ventricle (LV). The water intake was measured every 30 min over a period of 120 min. The sodium, potassium and urinary volume were measured over a period of 120 min in water-loaded rats. The injection of ANGII into the LV increased the water intake, which was reduced by previous injection of clonidine (an alpha-2-adrenergic agonist) into the LH. The injection of yohimbine (an alpha-2-adrenergic antagonist) and prazosin (an alpha-1-adrenergic antagonist) into the LH, which was done before injecting ANGII into the LV, also reduced the water intake induced by ANGII. The injection of ANGII into the LV reduced the sodium, potassium and urinary volume. Previous treatment with clonidine attenuated the action of ANGII in reducing the sodium, potassium and urinary volume, whereas previous treatment with yohimbine attenuated the effects of ANGII but with less intensity than that caused by clonidine. Previous treatment with prazosin increased the inhibitory effects of ANGII in those parameters. The injection of yohimbine and prazosin, which was done before the injection of clonidine, attenuated the effect of clonidine on the ANGII mechanism. The results of this study led us to postulate that when alpha-2-adrenergic receptors are blocked, the clonidine may act on the imidazoline receptors to produce its effects on the ANGII mechanism. We may also conclude that the LH is involved with circumventricular structures, which present excitatory and inhibitory mechanisms. Such mechanisms are responsible for regulating the renal excretion of sodium, potassium and water.

Effect of injection of L-NAME on drinking response.

The drinking behavior responses to centrally administered N G-nitro-L-arginine methyl ester (L-NAME; 10, 20 or 40 microg/microl), an inhibitor of nitric oxide synthase, were studied in satiated rats, with cannulae stereotaxically implanted into the lateral ventricle (LV) and subfornical organ (SFO). Water intake increased in all animals after angiotensin II (ANG II) injection into the LV, with values of 14.2 +/- 1.4 ml/h. After injection of L-NAME at doses of 10, 20 or 40 microg/microl into the SFO before injection of ANG II (12 ng/microl) into the LV, water intake decreased progressively and reached basal levels after treatment with 0.15 M NaCl and with the highest dose of L-NAME (i.e., 40 microg). The water intake obtained after 40 microg/microl L-NAME was 0.8 +/- 0.01 ml/h. Also, the injection of L-NAME, 10, 20 or 40 microg/microl, into the LV progressively reduced the water intake induced by hypertonic saline, with values of 5.3 +/- 0.8, 3.2 +/- 0.8 and 0.7 +/- 0.01 ml/h, respectively. These results indicate that nitric oxide is involved in the regulation of drinking behavior induced by centrally administered ANG II and cellular dehydration and that the nitric oxide of the SFO plays an important role in this regulation.

Effect of injection of L-NAME on drinking response

The drinking behavior responses to centrally administered NG-nitro-L-arginine methyl ester (L-NAME; 10, 20 or 40 µg/µl), an inhibitor of nitric oxide synthase, were studied in satiated rats, with cannulae stereotaxically implanted into the lateral ventricle (LV) and subfornical organ (SFO). Water intake increased in all animals after angiotensin II (ANG II) injection into the LV, with values of 14.2 + or - 1.4 ml/h. After injection of L-NAME at doses of 10, 20 or 40 µg/µl into the SFO before injection of ANG II (12 ng/µl) into the LV, water intake decreased progressively and reached basal levels after treatment with 0.15 M NaCl and with the highest dose of L-NAME (i.e., 40 µg). The water intake obtained after 40 µg/µl L-NAME was 0.8 + or - 0.01 ml/h. Also, the injection of L-NAME, 10, 20 or 40 µg/µl, into the LV progressively reduced the water intake induced by hypertonic saline, with values of 5.3 + or - 0.8, 3.2 + or - 0.8 and 0.7 + or - 0.01 ml/h, respectively. These results indicate that nitric oxide is involved in the regulation of drinking behavior induced by centrally administered ANG II and cellular dehydration and that the nitric oxide of the SFO plays an important role in this regulation.

Renal effects of angiotensin II receptor subtype 1 and 2-selective ligands injected into the paraventricular nucleus of conscious rats.

We determined the effects of losartan and CGP42112A (selective ligands of the AT1 and AT2 angiotensin receptors, respectively) and salarasin (a relatively nonselective angiotensin receptor antagonist) on urinary volume and urinary sodium and potassium excretion induced by administration of angiotensin II (ANG II) into the paraventricular nucleus (PVN) of conscious rats. Both the AT1 and AT2 ligands and salarasin administered in the presence of ANG II elicited a concentration-dependent inhibition of urine excretion, but losartan inhibited only 75% of this response. The IC50 for salarasin, CGP42112A, and losartan was 0.01, 0.05, and 6 nM, respectively. Previous treatment with saralasin, CGP42112A and losartan competitively antagonized the natriuretic responses to PVN administration of ANG II, and the IC50 values were 0.09, 0.48, and 10 nM, respectively. The maximum response to losartan was 65% of that obtained with saralasin. Pretreatment with saralasin, losartan, and CGP42112A injected into the PVN caused shifts to the right of the concentration-response curves, but the losartan concentrations were disproportionately greater compared with salarasin or CGP42112A. The IC50 values were 0.06, 0.5, and 7.0 for salarasin, CGP42112A, and losartan, respectively. These results suggest that both AT1 and AT2 receptor subtypes in the PVN are involved in ANG II-related urine, sodium, and potassium excretion, and that the inhibitory responses to AT2 blockade are predominant.

Effects of the alpha antagonists and agonists injected into the lateral hypothalamus on the water and sodium intake induced by angiotensin II injection into the subfornical organ.

The subfornical organ (SFO) and the lateral hypothalamus (LH) have been shown to be important for the central action of angiotensin II (ANG II) on water and salt regulation. Several anatomical findings have demonstrated neural connections between the SFO and the LH. The present experiments were conducted to investigate the role of the alpha-adrenergic antagonists and agonists injected into the LH on the water and salt intake elicited by injections of ANG II into the SFO. Prazosin (an alpha1-adrenergic antagonist) injected into the LH increased the salt ingestion, whereas yohimbine (an alpha2-adrenergic antagonist) and propranolol (a beta-adrenergic antagonist) antagonized the salt ingestion induced by administration of ANG II into the SFO. Previous administration of clonidine (an alpha2-adrenergic agonist) or noradrenaline into the LH increased, whereas pretreatment with phenylephrine decreased the sodium intake induced by injection of ANG II into the SFO. Previous treatment with prazosin and propranolol reduced the water intake induced by ANG II. Phenylephrine increased the dipsogenic responses produced by ANG II, whereas previous treatment with clonidine injected into the LH reduced the water intake induced by ANG II administration into the SFO. The LH involvement with SFO on the excitatory and inhibitory mechanisms related to water and sodium intake is suggested.

Role of angiotensin II and vasopressin receptors within the supraoptic nucleus in water and sodium intake induced by the injection of angiotensin II into the medial septal area

In this study we investigated the effects of the injection into the supraoptic nucleus (SON) of non-peptide AT1- and AT2-angiotensin II (ANG II) receptor antagonists, DuP753 and PD123319, as well as of the arginine-vasopressin (AVP) receptor antagonist d(CH2)5-Tyr(Me)-AVP, on water and 3 percent NaCl intake induced by the injection of ANG II into the medial septal area (MSA). The effects on water or 3 percent NaCl intake were assessed in 30-h water-deprived or in 20-h water-deprived furosemide-treated adult male rats, respectively. The drugs were injected in 0.5 µl over 30-60 s. Controls were injected with a similar volume of 0.15 M NaCl. Antagonists were injected at doses of 20, 80 and 180 nmol. Water and sodium intake was measured over a 2-h period. Previous administration of the AT1 receptor antagonist DuP753 into the SON decreased water (65 percent, N = 10, P<0.01) and sodium intake (81 percent, N = 8, P<0.01) induced by the injection of ANG II (10 nmol) into the MSA. Neither of these responses was significantly changed by injection of the AT2-receptor antagonist PD123319 into the SON. On the other hand, while there was a decrease in water intake (45 percent, N = 9, P<0.01), ANG II-induced sodium intake was significantly increased (70 percent, N = 8, P<0.01) following injection of the V1-type vasopressin antagonist d(CH2)5-Tyr(Me)-AVP into the SON. These results suggest that both AT1 and V1 receptors within the SON may be involved in water and sodium intake induced by the activation of ANG II receptors within the MSA. Furthermore, they do not support the involvement of MSA AT2 receptors in the mediation of these responses