Subfornical organ mediates pressor effect of angiotensin: Influence of nitric oxide synthase inhibitors, AT(1) and AT(2) angiotensin antagonist's receptors.

We investigated the influence of voltage-dependent calcium channels and nitric oxide (NO) on angiotensin II (ANG II)-pressor effect injected into subfornical organ (SFO). The influence of NO on nifedipine antipressor action has also been studied by utilizing N(W)-nitro-L-arginine methyl ester (L-NAME) (20 mug x 0.2 mul(-1)) a nitric oxide synthase inhibitor (NOSI) and 7-nitroindazole (7-NIT) (20 mug x 0.2 mul(-1)), a specific neuronal nitric oxide synthase inhibitor (nNOSI). We have also investigated the role of losartan and PD123319, selective ANG II AT(1) and AT(2) receptor nonpeptide antagonists, in the pressor effect of ANG II and in the effect of L-NAME and 7-NIT, injected into the SFO. Adult male Holtzman rats (220 to 280 g) were anesthetized with ketamine (80 mg/kg(-1) of body weight) plus xylazine (7 mg/kg(-1) of body weight), placed in a stereotaxic apparatus (David Kopf model for rats), and implanted with cannula into the SFO. Direct mean arterial blood pressure (MAP) was recorded in conscious rats in a test cage, without access to food or water. The previously implanted catheter into femoral artery was connected to a Statham (P23 Db) pressure transducer (Statham-Gould, Valley View, OH) coupled to a multichannel recorder (PowerLab Multirecord). MAP increased after ANG II injection. Pre-treatment with nifidipine (50 mug x 0.2 mul(-1) or 100 mug x 0.2 mul(-1)) followed by 25 pmol x 0.2 mul(-1) of ANG II, decreased ANG II-pressor effect. L-NAME and 7-NIT increased the elevation in MAP induced by ANG II, which was blocked by the prior injection of nifedipine. The AT(1) angiotensin antagonist losartan injected into the SFO blocked the effect of ANG II and the effects of L-NAME and 7-NIT while PD123319 did not. These results provide evidence that ANG II-pressor effect is influenced by nitrergic pathways that utilize L-type calcium channels in the SFO.

Activation of paraventricular nucleus of hypothalamus 5-HT1A receptor on sodium intake.

Hypothalamic paraventricular nucleus (PVN) has an important role in the regulation of water and sodium intake. Several researches described the presence of 5-HT(1) receptors in the central nervous system. 5-HT(1A) was one of the prime receptors identified and it is found in the somatodendritic and post-synaptic forms. Therefore, the aim of this study was to investigate the participation of serotonergic 5-HT(1A) receptors in the PVN on the sodium intake induced by sodium depletion followed by 24 h of deprivation (injection of the diuretic furosemide plus 24 h of sodium-deficient diet). Rats (280-320 g) were submitted to the implant of cannulas bilaterally in the PVN. 5-HT injections (10 and 20 microg/0.2 microl) in the PVN reduced NaCl 1.8% intake. 8-OH-DPAT injections (2.5 and 5.0 microg/0.2 microl) in the PVN also reduced NaCl 1.8% intake. pMPPF bilateral injections (5-HT(1A) antagonist) previously to 8-OH-DPAT injections have completely blocked the inhibitory effect over NaCl 1.8% intake. 5-HT(1A) antagonists partially reduced the inhibitory effect of 5-HT on NaCl 1.8% intake induced by sodium depletion. In contrast, the intake of palatable solution (2% sucrose) under body fluid-replete conditions was not changed after bilateral PVN 8-OH-DPTA injections. The results show that 5-HT(1A) serotonergic mechanisms in the PVN modulate sodium intake induced by sodium loss. The finding that sucrose intake was not affected by PVN 5-HT(1A) activation suggests that the effects of the 5-HT(1A) treatments on the intake of NaCl are not due to mechanisms producing a nonspecific decrease of all ingestive behaviors.

Interaction between arginine vasopressin and angiotensin II receptors in the central regulation of sodium balance.

We speculated that the influence of lateral preoptic area (LPO) in sodium balance, involves arginine8-vasopressin (AVP) and angiotensin (ANG II) on Na+ uptake in LPO. Therefore, the present study investigated the effects of central administration of specific AVP and ANG II antagonists (d(CH2)5-Tyr (Me)-AVP (AAVP) and [Adamanteanacetyl1, 0-ET-d-Tyr2, Val4, Aminobutyryl6, Arg(8,9)]-AVP (ATAVP) antagonists of V1 and V2 receptors of AVP. Also the effects of losartan and CGP42112A (selective ligands of the AT1 and AT2 angiotensin receptors, respectively), was investigated on Na+ uptake and renal fluid and electrolyte excretion. After an acclimatization period of 7 days, the animals were maintained under tribromoethanol (200 mg/kg body weight, intraperitonial) anesthesia and placed in a Kopf stereotaxic instrument. Stainless guide cannula was implanted into the LPO. AAVP and ATAVP injected into the LPO prior to AVP produced a reduction in the NaCl intake. Both the AT1 and AT2 ligands administered into the LPO elicited a decrease in the NaCl intake induced by AVP injected into the LPO. AVP injection into the LPO increased sodium renal excretion, but this was reduced by prior AAVP administration. The ATAVP produced a decreased in the natriuretic effect of AVP. The losartan injected into LPO previous to AVP decreased the sodium excretion and the CGP 421122A also decreased the natriuretic effect of AVP. The AVP produced an antidiuresis effect that was inhibited by prior administration into LPO of the ATAVP. The AAVP produced no change in the antidiuretic effect of AVP. These results suggest that LPO are implicated in sodium balance that is mediated by V1, V2, AT1 and AT2 receptors.

Lateral hypothalamus lesions influences water and salt intake, and sodium and urine excretion, and arterial blood pressure induced by L-NAME and FK 409 injections into median preoptic nucleus in conscious rats.

Male Holtzman rats weighting 200-250 g were anesthetized with zoletil 50 mg/Kg (tiletamine chloridrate 125,0 mg and zolazepan chloridrate 125,0 mg) into quadriceps muscle and submitted an electrolytic lesion of the lateral hypothalamus (LH) and a stainless steel cannula was implanted into their median preoptic nucleus (MnPO). We investigated the effects of the injection into the (MnPO) of FK 409 (20 microg/0.5 microl), a nitric oxide (NO) donor, and N(W)-nitro-L-arginine methyl ester (L-NAME) 40 microg/0.5 microl, a nitric oxide synthase inhibitor (NOSI), on the water and sodium appetite and the natriuretic, diuretic and cardiovascular effects induced by injection of L-NAME and FK 409 injected into MnPO in rats with LH lesions. Controls were injected with a similar volume of 0.15 M NaCl. L-NAME injected into MnPO produced an increase in water and sodium intake and in sodium and urine excretion and increase de mean arterial pressure (MAP). FK 409 injected into MnPO did not produce any change in the hydro electrolytic and cardiovascular parameters in LH-sham and lesioned rats. FK 409 injected before L-NAME attenuated its effects. These data show that electrolytic lesion of the LH reduces fluid and sodium intake as well as sodium and urine excretion, and the pressor effect induced by L-NAME. LH involvement with NO of the MnPO excitatory and inhibitory mechanisms related to water and sodium intake, sodium excretion and cardiovascular control is suggested.

Influence of angiotensin II receptor subtypes of the paraventricular nucleus on the physiological responses induced by angiotensin II injection into the medial septal area.

OBJECTIVE: We determined the effects of losartan and PD 123319 (antagonists of the AT1 and AT2 angiotensin receptors, respectively), and [Sar1, Ala8] ANG II (a relatively peptide antagonist of angiotensin receptors) injected into the paraventricular nucleus (PVN) on water and 3% NaCl intake, and the diuretic, natriuretic, and pressor effects induced by administration of angiotensin II (ANG II) into the medial septal area (MSA) of conscious rats. METHODS: Holtzman rats were used. Animals were anesthetized with tribromoethanol (20 mg) per 100 grams of body weight, ip. A stainless steel guide cannula was implanted into the MSA and PVN. All drugs were injected in 0.5-microl volumes for 10-15 seconds. Seven days after brain surgery, water and 3% NaCl intake, urine and sodium excretion, and arterial blood pressure were measured. RESULTS: Losartan (40 nmol) and [Sar1, Ala8] ANG II (40 nmol) completely eliminated whereas PD 123319 (40 nmol) partially blocked the increase in water and sodium intake and the increase in arterial blood pressure induced by ANG II (10 nmol) injected into the MSA. The PVN administration of PD 123319 and [Sar1, Ala8] ANG II blocked whereas losartan attenuated the diuresis and natriuresis induced by MSA administration of ANG II. CONCLUSION: MSA involvement with PVN on water and sodium homeostasis and arterial pressure modulation utilizing ANGII receptors is suggested.

Influência dos subtipos dos receptores da angiotensina II do núcleo paraventricular sobre as respostas fisiológicas induzidas pela angiotensina II injetada na área septal medial / Influence of angiotensin II receptor subtypes of the paraventricular nucleus on the physiological responses induced by angiotensin II injection into the medial septal area

OBJECTIVE: We determined the effects of losartan and PD 123319 (antagonists of the AT1 and AT2 angiotensin receptors, respectively), and [Sar , Ala8] ANG II (a relatively peptide antagonist of angiotensin receptors) injected into the paraventricular nucleus (PVN) on water and 3 percent NaCl intake, and the diuretic, natriuretic, and pressor effects induced by administration of angiotensin II (ANG II) into the medial septal area (MSA) of conscious rats. METHODS: Holtzman rats were used . Animals were anesthetized with tribromoethanol (20 mg) per 100 grams of body weight, ip. A stainless steel guide cannula was implanted into the MSA and PVN. All drugs were injected in 0.5-mul volumes for 10-15 seconds. Seven days after brain surgery, water and 3 percent NaCl intake, urine and sodium excretion, and arterial blood pressure were measured. RESULTS: Losartan (40 nmol) and [Sar , Ala8] ANG II (40 nmol) completely eliminated whereas PD 123319 (40 nmol) partially blocked the increase in water and sodium intake and the increase in arterial blood pressure induced by ANG II (10 nmol) injected into the MSA. The PVN administration of PD 123319 and [Sar , Ala8] ANG II blocked whereas losartan attenuated the diuresis and natriuresis induced by MSA administration of ANG II. CONCLUSION: MSA involvement with PVN on water and sodium homeostasis and arterial pressure modulation utilizing ANGII receptors is suggested

Novel evidence that nitric oxide of the medial septal area influences the salivary secretion induced by pilocarpine.

Our studies have focused on the effect of injection of L-NAME and sodium nitroprussiate (SNP) on the salivary secretion, arterial blood pressure, sodium excretion and urinary volume induced by pilocarpine which was injected into the medial septal area (MSA). Rats were anesthetized with urethane (1.25 g/kg b. wt.) and a stainless steel cannula was implanted into their MSA. The amount of saliva secretion was studied over a five-minute period after injection of pilocarpine into MSA. Injection of pilocarpine (10, 20, 40, 80, 160 microg/microl) into MSA produced a dose-dependent increase in salivary secretion. L-NG-nitro arginine methyl-esther (L-NAME) (40 microg/microl), a nitric oxide (NO) synthase inhibitor, was injected into MSA prior to the injection of pilocarpine into MSA, producing an increase in salivary secretion due to the effect of pilocarpine. Sodium nitroprussiate (SNP) (30 microg/microl) was injected into MSA prior to the injection of pilocarpine into MSA attenuating the increase in salivary secretion induced by pilocarpine. Medial arterial pressure (MAP) increase after injections of pilocarpine into the MSA. L-NAME injected into the MSA prior to injection of pilocarpine into MSA increased the MAP. SNP injected into the MSA prior to pilocarpine attenuated the effect of pilocarpine on MAP. Pilocarpine (40 ug/ul) injected into the MAS induced an increase in sodium and urinary excretion. L-NAME injected prior to pilocarpine into the MSA increased the urinary sodium excretion and urinary volume induced by pilocarpine. SNP injected prior to pilocarpine into the MSA decreased the sodium excretion and urinary volume induced by pilocarpine. All these roles of pilocarpine depend on the release of nitric oxide into the MSA. We may also conclude that the MSA is involved with the cholinergic excitatory mechanism that induce salivary secretion, increase in MAP and increase in sodium excretion and urinary volume.

Effect of adrenergic stimulation of the amygdalois complex on water intake

O efeito da noradrenalina, isoproterenol, fentolamina e propanolol, injetados no núcleo basolateral da amigdala, sobre a ingestäo de água, foi investigado em ratos Holtzman. A injeçäo de noradrenalina (40nmol) no complexo amigdalóide (CA) de ratos saciados näo produziu nenhuma mudança na ingestäo de água em ratos saciados (1,93 ñ 0,23 ml/lh). A noradrenalina injetada no CA produziu uma diminuiçäo na ingestäo de água de ratos privados (0,40 ñ 0,19 ml/lh). A injeçäo de isoproterenol no CA de ratos privados näo produziu nenhuma mudança na ingestäo de água em comparaçäo aos controles (11,65 ñ 1,02 e 10,92 ñ 0,88 ml/lh, respectivamente). Quando comparado com valores controles, a fentolamina injetada prévia à noradrenalina bloqueou o efeito inibitório da noradrenalina sobre a ingestäo de água em ratos privados 10,40 ñ 1,31 ml/lh). O propanolol bloqueou o efeito do isorpoterenol em ratos saciados (0,85 ñ 0,49 ml/lh) e também bloqueou a ingestäo água induzida por privaçäo (0,53 ñ 0,38 ml/lh). Tanto em animais saciados quanto em privados, a injeçäo de fentolamina, antes da administraçäo de hexametônio, bloqueou o efeito inibitório do hexametônio na ingestäo de água. Em animais saciados, quando o hexametônio foi injetado sozinho, a ingestäo de água foi de 0,39 ñ 0,25 ml/lh; quando acompanhado de fentolamina, a ingestäo de água foi de 1,04 ñ 0,3 ml/lh. Em ratos privados, o hexametônio sozinho bloqueou a ingestäo de água (0,40 ñ 0,17 ml/lh) e quando injetado com fentolamina produziu uma ingestäo de 9,7 ñ 1,8 ml/lh. Este resultados demonstram claramente a participaçäo de receptores catecolaminérgicos do CA na regulaçäo da ingestäo de água.

Effect of nicotinic stimulation of the amygdaloid complex on water and sodium chloride intake

No presente trabalho foi estudado o efeito da estimulaçäo e nicotínica do complexo amigdalóide (CA) sobre a ingestäo de sódio e água em ratos saciados e privados de água. A nicotina näo produziu nenhuma alteraçäo no apetite ao sódio e água em ratos saciados. Em ratos privados, a nicotina injetada no núcleo basolateral somente bloqueou a ingestäo de cloreto de sódio. Nós demonstramos previamente que o carbacol, injetado no CA, inibiu a ingestäo de água e cloreto de sódio em ratos saciados e privados de água. A injeçäo de hexametônio no CA bloqueou totalmente a ingestäo de água em ratos saciados e privados de água. A administraçäo de hexametônio no CA, antes da injeçäo de nicotina,näo produziu alteraçäo na ingestäo de sódio. Assim, estes resultados sugerem que a populaçäo de neurônios colinoceptivos específicos do CA medeiam a ingestäo de água e cloreto de sódio

Participation of the ß-adrenoceptors of the medial septal area on urine flow rate, sodium and potassium excretion

Investigou-se a participaçäo dos ß-adrenoceptores da área septal (AS) na excreçäo urinária de sódio, potássio e fluxo urinário. As alteraçöes na pressäo arterial e algumas funçöes renais foram também investigadas. A injeçäo de 2.10-8 à 16.10-8 M de isoproterenol, através de cânulas de demora implantadas permanentemente na AS, produziu uma diminuiçäo significante dose-dependente na excreçäo urinária de sódio, potássio e fluxo urinário. Pré-tratamento com 16.10-8 M de butoxamina antagonizou o efeito de 4.10-8 M de isoproterenol mas o pré-tratamento com 16.10-8 M de practolol näo aboliu o efeito do isoproterenol. Os ß2 agonistas, terbutalina e salbutamol (4.10-8 M) quando injetados intraseptalmente produziram também um decréscimo no fluxo urinário e na excreçäo de sódio e potássio. Após injeçäo de isoproterenol ou salbutamol (4.10-8 M) na AS, a pressäo arterial, taxa de filtraçäo glomerular (TFG) e a filtraçäo de sódio foram reduzidas, enquanto que a fraçäo de reabsorçäo de sódio foi aumentada. Os resultados indicam que os ß2 adrenoceptores da AS tem influência na diminuiçäo de sódio, potássio e fluxo urinário e este efeito pode ser devido a queda na TFG e no sódio filtrado e pelo aumento na reabsorçäo tubular de sódio

Sistema renina-angiotensina cerebral e sua interaçäo com o sistema renina-angiotensina renal / Interaction between central and peripheric renin-angiotensin system

O objetivo deste trabalho foi o de investigar a existência de angiotensina II (AII) no líquido cefalorraquideano (LCR) independente daquela originada nos rins. A concentraçäo de AII foi medida no LCR de ratos normais e nefrectomizados, tratados com AII central ou perifericamente, isoproterenol e polietilenoglicol. Nos animais nefrectomizados, houve um aumento de quatro vezes da AII no LCR em relaçäo aos animais normais. Quando se fez a infusäo intravenosa de AII, nenhuma mudança nos níveis de AII no LCR foi detectada. A aplicaçao do isoproterenol e do polietilenoglicol provocaram uma diminuiçao nos níveis de AII no LCR de ratos normais, mas näo nos nefrectomizados. Esses resultados mostraram que existe AII no LCR tendo interaçäo com a AII vinda do sangue, sugerindo a existência de um sistema renina-angiotensina cerebal. Os efeitos observados durante hipotensäo e hipovolemia sugerem um mecanismo autorregulatório entre AII sistêmica (renal) e renina cerebal

Variaçäo dos níveis séricos de glicose, triglicerídeos, colesterol e HDL-colesterol em ratos submetidos a lesöes do hipotálamo lateral / Variations of serum levels of glucose, triglycerides, cholesterol and HDL-cholesterol in rats submitted to lesions of lateral hypothalamus

Vários núcleos hipotalâmicos (núcleo ventromediano, hipotálamo lateral, etc.) atuam regulando a atividade enzimática envolvida no metabolismo de lipídeos e carboidratos. Neste trabalho procurou-se avaliar a participaçäo do hipotálamo lateral (HL) nos níveis séricos de glicose, triglicerídeos, colesterol e HDL-colesterol e verificar as variaçöes do peso corpóreo e ingestäo de alimentos - água e raçäo - em ratos controle e ratos submetidos a lesöes eletrolíticas bilaterais do hipotálamo lateral (HL). Foram utilizados ratos Holtzman de peso variável entre 250-300 gramas para as lesöes, e após períodos de 24, 48 horas, 7, 10 e 25 dias os animais lesados foram anestesiados, coletou-se sangue da aorta descendente abdominal e procedeu-se às dosagens bioquímicas e mediçöes da ingestäo de raçäo e água. Os resultados obtidos para os níveis séricos de glicose demonstraram aumento no grupo 24 horas lesäo do hipotálamo lateral (HL) e diminuiçäo nos grupos lesados de 7, 10 e 25 dias em relaçäo ao grupo controle. Para os níveis séricos de triglicerídeos observou-se uma diminuiçäo nos grupos lesados de 24, 48 e 10 dias, em relaçäo ao grupo controle. Os níveis séricos de colesterol apresentaram aumento nos grupos lesados de 48 horas e 25 dias quando comparados ao grupo controle. Os níveis séricos de HDL-colesterol aumentaram no grupo 48 horas de lesäo em relaçäo ao grupo controle. Em todos os grupos de animais com lesäo do hipotálamo lateral (HL) notaram-se alteraçöes características no peso corporal e ingestäo de alimento (raçäo e água). Os resultados demonstraram que a lesäo bilateral do hipotálamo lateral (HL) promove alteraçöes nos níveis séricos de glicose, triglicerídeos, colesterol e HDL-colesterol

Morphological alterations of the rat submandibular gland caused by lesion of the ventromedial nucleus of the hypothalamus

As características morfológicas da glândula submandibular de ratos foram estudadas em diferentes períodos de tempo (5, 10, 20, 40 e 90 dias) após a lesäo do núcleo ventromedial do hipotálamo. O arranjo estrutural da glândula submandibular foi o mesmo em ratos com lesäo do núcleo ventromedial e nos ratos controle ou com lesäo fictícia. No primeiro grupo, entretanto, o septo estava estreito, dificultando a definiçäo dos compartimentos lobulares. Alteraçöes do parênquima foram bastante evidentes nos ratos lesados, com hipotrofia acinar e aumento no número de ductos granulosos. Os componentes submandibulares restantes, entretanto, näo apresentaram alteraçöes quando comparados com aqueles dos animais controles. Em resumo, a lesäo do núcleo ventromedial do hipotálamo produz as seguintes mudanças na glândula submandibular do rato: 1) diminuiçäo da massa glandular; 2) hipotrofia acinar; e 3) aumento no número de ductos granulosos

O efeito de hormônios neurohipofisários sobre a excreçäo de eletrólitos em ratos / The effect of neurohypophyseal hormones on the excretion of electrolytes in rats

Os autores estudaram o efeito da infusäo endovenosa de uma soluçäo aquosa de HAD e ocitocina, em diferentes períodos de tempo. Pela análise dos resultados verificaram que ambos os hormônios alteram significantemente a excreçäo urinária de água e sódio. Contudo, a excreçäo renal de potássio nem sempre acompanhou o pico de excreçäo de sódio. Os dados sugerem uma inibiçäo da reabsorçäo de sódio ao nível do túbulo proximal para distal