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.

Imidazoline receptors of the paraventricular nucleus on the pressor response induced by stimulation of the subfornical organ.

In the present experiments we investigated a possible involvement of imidazoline receptors of the paraventricular nucleus (PVN) of the hypothalamus on the pressor effects of the angiotensin II (ANG II) injected into the subfornical organ (SFO), in male Holtzman rats (250-300 g) with a cannula implanted into the third ventricle (3rdV), PVN and SFO. At first we tested the participation of alpha 2 and imidazoline agonist and antagonist compounds on the pressor effect of ANG II injected into the 3rdV. Based on the results we may conclude that clonidine associated with rilmenidine was able to block the hypertensive response to ANG II. The ANG II (20 pmol) injected into SFO induced a robust increase in blood pressure (37 +/- 2 mmHg). Isotonic saline (0.15 M) NaCl did not produce any change in blood pressure (5 +/- 2 mmHg). The injection of rilmenidine (30 micrograms/kg/1 microL), an imidazoline agonist agent injected into PVN before ANG II injection into SFO, blocked the pressor effect of ANG II (5 +/- 2 mmHg). Also, the injection of idazoxan (60 micrograms/kg/microL) before rilmenidine blocked the inhibitory effect of rilmenidine on blood pressure (39 +/- 4 mmHg). The injection of clonidine (20 nmol/microL) prior to ANG II into the 3rdV produced a decreased in arterial blood pressure (37 +/- 2 mmHg) to (15 +/- 4 mmHg). The injection of yohimbine (80 nmol/microL) prior to clonidine blocked the effect of clonidine on the effect of ANG II (27 +/- 2 mmHg). The injection of rilmenidine prior to ANG II also induced a decrease in arterial blood pressure (10 +/- 3 mmHg). The injection of idazoxan prior to rilmenidine also blocked the inhibitory effect of rilmenidine (24 +/- 3 mmHg). In summary, the present study demonstrated that rilmenidine decreases the hypertensive effect of ANG II, with more potency than clonidine, even when injected into 3rdV or PVN. This study established that the PVN interacts with SFO by imidazoline receptors in order to control the arterial blood pressure.

Ibotenate lesion of the medial hypothalamus alters the salt intake and pressor responses to activation of the median preoptic nucleus in rats.

We investigated the influence of ibotenic acid lesions of the medial hypothalamus (MH) on salt appetite and arterial blood pressure responses induced by angiotensinergic and adrenergic stimulation of the median preoptic nucleus (MnPO) of rats. Previous injection of the adrenergic agonists norepinephrine, clonidine, phenylephrine, and isoproterenol into the MnPO of sham MH-lesioned rats caused no change in the sodium intake induced by ANG II. ANG II injected into the MnPO of MH-lesioned rats increased sodium intake compared with sham-lesioned rats. Previous injection of clonidine and isoproterenol increased, whereas phenylephrine abolished the salt intake induced by ANG II into the MnPO of MH-lesioned rats. Previous injection of norepinephrine and clonidine into the MnPO of sham MH-lesioned rats caused no change in the mean arterial pressure (MAP) induced by ANG II. Under the same conditions, previous injection of phenylephrine increased, whereas isoproterenol reversed the increase in MAP induced by angiotensin II (ANG II). ANG II injected into the MnPO of MH-lesioned rats induce a decrease in MAP compared with sham-lesioned rats. Previous injection of phenylephrine or norepinephrine into the MnPO of MH-lesioned rats induced a negative MAP, whereas pretreatment with clonidine or isoproterenol increased the MAP produced by ANG II injected into the MnPO of sham- or MH-lesioned rats. These data show that ibotenic acid lesion of the MH increases the sodium intake and pressor responses induced by the concomitant angiotensinergic, alpha 2 and beta adrenergic activation of the MnPO, whereas alpha 1 activation may have opposite effects. MH involvement in excitatory and inhibitory mechanisms related to sodium intake and MAP control is suggested.

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 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.

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.

Role of adrenergic pathways of the medial preoptic area in ANGII-induced water intake and renal excretion in rats.

In this study, we investigated the participation of adrenergic neurotransmission in angiotensin II- (ANGII)-induced water intake and urinary electrolyte excretion by means of injection of the alpha 1-, alpha 2-, and beta-adrenoceptor antagonists and ANGII into the medial preoptic area (MPOA) in rats. Prazosin (an alpha 1-adrenergic antagonist) antagonized the water ingestion, Na+, K+ and urine excretion induced by ANGII, whereas yohimbine (an alpha 2-adrenergic antagonist) enhanced the Na+, K+ and urine excretion induced by ANGII. Propranolol (a nonselective beta-adrenoceptor blocker) antagonized the water ingestion and enhanced the Na+, and urine excretion induced by ANGII. Previous treatment with prazosin reduced the pressor responses to ANGII, whereas yohimbine had opposite effects. Previous injection of propranolol produced no effects in the pressor responses to ANGII. These results suggest that the adrenergic neurotransmission in the MPOA may actively participate in ANGII-induced dipsogenesis, natriuresis, kaliuresis and diuresis in a process that involves alpha 1-, alpha 2-, and beta-adrenoceptors.

Lesion of the anteroventral third ventricle region impairs the recovery of arterial pressure induced by hypertonic saline in rats submitted to hemorrhagic shock.

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.

AV3V lesion suppresses the pressor, dipsogenic and natriuretic responses to cholinergic activation of the septal area in rats.

In the present study we investigated the effect of anteroventral third ventricle (AV3V) lesion on pressor, dipsogenic, natriuretic and kaliuretic responses induced by the injection of carbachol (a cholinergic agonist) into the medial septal area (MSA) of rats. Male rats with sham or AV3V lesion and a stainless-steel cannula implanted into the MSA were used. Carbachol (2 nmol) injected into the MSA in sham lesion rats produced pressor (43 +/- 2 mmHg), dipsogenic (9.6 +/- 1.2 ml/h), natriuretic (531 +/- 82 microEq/120 min) and kaliuretic (164 +/- 14 microEq/120 min) responses. In AV3V-lesioned rats (1-5 days and 14-18 days), the pressor (11 +/- 2 and 14 +/- 2 mmHg, respectively), dipsogenic (1.9 +/- 0.7 and 1.4 +/- 0.6 ml/h), natriuretic (21 +/- 5 and 159 +/- 44 microEq/120 min) and kaliuretic (124 +/- 14 and 86 +/- 13 microEq/120 min) responses induced by carbachol injection into the MSA were reduced. These results show that the AV3V region is essential for the pressor, dipsogenic, natriuretic and kaliuretic responses induced by cholinergic activation of the MSA in rats.

Clonidine and phenylephrine injected into the lateral hypothalamus inhibits water intake in rats.

It has been demonstrated that peripheral or intracerebroventricular (i.c.v.) administration of the alpha 2-adrenoceptor agonist, clonidine, blocks the water intake induced by several dipsogenic stimuli in rats. In the present investigation we studied the effect of the injection of clonidine, phenylephrine, prazosin or yohimbine into the lateral hypothalamic area (LHA) on the water intake induced by water deprivation or central angiotensin II (AII) in rats. Rats with chronic cannulas implanted into the lateral ventricle and LHA were used. Injection of clonidine or phenylephrine into the LHA reduced the water intake produced by both water deprivation and i.c.v. injection of AII. Previous injection of the alpha 1- or alpha 2-adrenoceptor antagonists, prazosin or yohimbine, into the LHA reduced the antidipsogenic effect of clonidine or phenylephrine injected into the same area. These results suggest that the alpha 1- and alpha 2-adrenergic receptors of the hypothalamus are part of the central inhibitory system for the thirst produced by dehydration or central AII.

Lesion of the anteroventral third ventricle region abolishes the beneficial effects of hypertonic saline on hemorrhagic shock in rats.

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.

Role of the alpha 1- and alpha 2-adrenoceptors of the lateral hypothalamus in the dipsogenic response to central angiotensin II in rats.

The present experiments were conducted to investigate the role of the alpha 1- and alpha 2-adrenergic receptors of the lateral hypothalamus (LH) on the drinking response elicited by intracerebroventricular (i.c.v.) injections of carbachol and angiotensin II (AII) in rats. Clonidine (an alpha 2-adrenergic agonist) injected into the LH produced a dose-dependent reduction of the drinking responses elicited by i.c.v. administration of carbachol and AII. The alpha 1-adrenergic agonist phenylephrine injected into the LH reduced the dipsogenic response to i.c.v. AII, but not to carbachol. Injection of yohimbine (an alpha 2-adrenergic antagonist) and prazosin (an alpha 1-adrenergic antagonist) into the LH also reduced the water intake produced by i.c.v. injection of AII. Previous injection of alpha 1- or alpha 2-adrenergic antagonists into the LH increased the antidipsogenic effect of clonidine or phenylephrine injected into the same area on the water intake induced by i.c.v. AII. These results show that the alpha 1- and alpha 2-adrenergic receptors of the LH are involved in the control of drinking responses elicited by i.c.v. injection of AII in rats. They also show that clonidine, but not phenylephrine, suppresses the drinking induced by i.c.v. carbachol. The data suggest that the discharge of central alpha-adrenergic receptors has a dual (inhibitory and excitatory) effect on water intake induced by central AII.

Role of the alpha 1-, and alpha 2- and beta-adrenoceptors of the median preoptic area on the water intake, renal excretion, and arterial pressure induced by ANG II.

The present experiments were conducted to investigate the role of the alpha 1-, alpha 2- and beta-adrenergic receptors of the median preoptic area (MnPO) on the water intake and urinary electrolyte excretion, elicited by central injections of angiotensin II (ANG II). Prazosin (an alpha 1-adrenergic receptor antagonist) and yohimbine (an alpha 2-adrenergic receptor antagonist) antagonized the water ingestion, Na+, K+, and urine excretion induced by ANG II. Administration of propranolol, a beta-adrenergic receptor antagonist increased the Na+, K+, and urine excretion induced by ANG II. Previous treatment with prazosin and yohimbine reduced the pressor responses to ANG II. These results suggest that the adrenergic neurotransmission in the MnPO may actively participate in ANG II-induced dipsogenesis, natriuresis, kaliuresis, diuresis and pressor responses in a process that involves alpha 1-, alpha 2-, and beta-adrenoceptors.

Role of alpha 1 and alpha 2-adrenoceptors of the lateral hypothalamic area on urinary excretion caused by centrally administered angiotensin II.

To determine whether central alpha 1 and alpha 2-adrenergic mechanisms are involved in urinary sodium and potassium excretion and urine volume induced by angiotensin II (ANGII), these renal parameters were measured in volume-expanded Holtzman rats with cannulas implanted into lateral ventricle (LV) and lateral hypothalamus (LH). The injection of ANGII into LV in rats with volume expansion reduced the sodium, potassium and urine excretion in comparison to the control injections of isotonic saline, whereas prazosin (alpha 1 antagonist) potentiated these effects. Clonidine (alpha 2 agonist) and yohimbine (alpha 2 antagonist) injected into LH previous to injection of ANGII into LV also abolished the inhibitory effect of ANGII. These results suggest that the discharge of central alpha-adrenergic receptors has dual inhibitory and excitatory effect on antinatriuretic, antikaliuretic and antidiuretic effect induced by central ANGII in volume-expanded rats.

Effect of furosemide treatment on the central and peripheral pressor responses to cholinergic and adrenergic agonists, angiotensin II, hypertonic solution and vasopressin.

The present study was performed to investigate the effect of treatment with furosemide on the pressor response induced by intracerebroventricular (i.c.v.) injections of cholinergic (carbachol) and adrenergic (norepinephrine) agonists, angiotensin II (ANGII) and hypertonic saline (HS, 2 M NaCl). The changes induced by furosemide treatment on the pressor response to intravenous (i.v.) norepinephrine, ANGII and arginine vasopressin (AVP) were also studied. Rats with a stainless-steel cannula implanted into the lateral ventricle (LV) were used. Two injections of furosemide (30 mg/kg b.wt. each) were performed 12 and 1 h before the experiments. Treatment with furosemide reduced the pressor response induced by carbachol, norepinephrine and ANGII i.c.v., but no change was observed in the pressor response to i.c.v. 2 M NaCl. The pressor response to i.v. ANGII and norepinephrine, but not AVP, was also reduced after treatment with furosemide. These results show that the treatment with furosemide impairs the pressor responses induced by central or peripheral administration of adrenergic agonist or ANGII, as well as those induced by central cholinergic activation. The results suggest that the treatment with furosemide impairs central and peripheral pressor responses mediated by sympathetic activation and ANGII, but not those produced by AVP.

Role of the adrenergic pathways of the lateral hypothalamus on water intake and pressor response induced by the cholinergic activation of the medial septal area in rats.

In the present experiments, we investigated a possible involvement of noradrenergic receptors of the lateral hypothalamus (LH) in the water intake and pressor response induced by cholinergic stimulation of the medial septal area (MSA) in rats. The cholinergic agonist carbachol (2 nmol) injected into the MSA induced water intake and pressor response. The injection of an alpha 2-adrenergic agonist, clonidine (20 and 40 nmol), but not of an alpha 1-adrenergic agonist, phenylephrine (80 and 160 nmol), into the LH inhibits the water intake induced by carbachol injected into the MSA. The injection of clonidine or phenylephrine into the LH produced no change in the MAP increase induced by carbachol injected into the MSA. The present results suggest that adrenergic pathways involving the LH are important for the water intake, but not for the pressor response, induced by cholinergic activation of the MSA.

The anteroventral third ventricle (AV3V) region is essential for pressor, dipsogenic and natriuretic responses to central carbachol.

In the present study we investigated the effect of anteroventral third ventricle (AV3V) lesion on pressor, dipsogenic and natriuretic responses produced by the intracerebroventricular (i.c.v.) injection of a cholinergic agonist (carbachol). Freely moving rats with AV3V or sham lesion (1-2 days and 9-12 days) and a delay cannula implanted into the lateral ventricle were studied. Changes in mean arterial pressure (MAP, 1 h record), water intake (1 h) and Na+ excretion (2 h) were analysed after i.c.v. injection of carbachol (7.5 nmol). In sham rats, i.c.v. injection of carbachol produced an increase in MAP (35 +/- 2 mmHg), water ingestion (7.7 +/- 1.2 ml/h) and Na+ excretion (626 +/- 42 microEq/120 min). The effects of i.c.v. carbachol injection were reduced 1-2 days after AV3V lesion (delta MAP = 6 +/- 2 mmHg, water ingestion = 0.3 +/- 0.3 ml/h and Na+ excretion = 31 +/- 11 microEq/120 min) and 9-12 days (delta MAP = 11 +/- 3 mmHg, water ingestion = 3.3 +/- 0.9 ml/h and Na+ excretion = 37 +/- 11 microEq/120 min). These results show that the AV3V region is essential for the full development of the pressor, dipsogenic and natriuretic responses produced by central cholinergic receptors.

Carbachol injection into the medial preoptic area induces natriuresis, kaliuresis and antidiuresis in rats.

The microinjection of carbachol into the medial preoptic area (MPO) of the rat induced natriuresis, kaliuresis and anti-diuresis in a dose-related manner. Atropine blocked all responses to carbachol. Hexamethonium impaired the dose-response effect of carbachol on kaliuresis, but had no effect on natriuresis and enhanced the antidiuretic effect of carbachol. Nicotine alone had no effects, but pre-treatment with nicotine enhanced the responses to carbachol. These data show that activity of the muscarinic receptors of the MPO increases renal electrolyte and reduces water excretion. They also suggest that nicotinic receptors have an inhibitory effect on water excretion. Nicotine could act through mechanisms unrelated to nicotinic receptors to enhance the effect of the carbachol.

Alterations in the water intake caused by central inhibition of angiotensin-converting enzyme in the rat.

In the present study we investigated the effects of central (i.c.v.) and subcutaneous (s.c.) injections of a 2 micrograms dose of lisinopryl, an inhibitor of angiotensin I(ANGI)-converting enzyme (CE), on water intake. I.c.v. but not s.c. injection of lisinopryl abolished drinking in response to s.c. isoprenaline (100 micrograms/kg) and significantly reduced drinking in response to 24 h water deprivation or s.c. polyethylene glycol (30% w/v, 10 ml/kg). Lisinopryl had no effect on water intake induced by cellular dehydration (s.c. injection of hypertonic saline (2 M NaCl)). These results are consistent with the hypothesis that lisinopryl acts as a CE blocking agent in the brain. The thrist challenge induced by hypotension using isoprenaline acts primarily by generating ANGII systemically and centrally. The other thirst challenges such as cellular dehydration are independent of the ANGII in the brain. This conclusion was made possible by utilizing a new CE blocking agent at a smaller dose than normally used for other ANG I-CE inhibitors.