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.

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.

Effect of electrolytic and chemical lesion by ibotenic acid of the septal area on water and salt intake.

Water and sodium chloride intake was studied in male Holtzman rats weighing 250-300 g that had been subjected to electrolytic and chemical lesions of the septal area (SA). Water intake increased in animals with electrolytic lesion of the SA bilaterally from 169.37+/-8.55 (sham) to 214.87+/-23.10 ml/5 days (lesioned). Water intake decreased after ibotenic acid lesion of the SA from 229.33+/-27.60 to 127.33+/-22.84 ml/5 days. Sodium chloride intake (1.5%) increased in animals with electrolytic lesion of the SA from 10.0+/-1.73 to 15.5+/-1.95 ml/5 days after lesion. Also sodium chloride (1.5%) intake increased after ibotenic acid injection into the SA to a greater extent (from 7.83+/-1.25 to 14.33+/-1.87 ml/5 days). The results indicate that the water intake response may be due to lesions that involve cell bodies and fibers of passage and that the sodium intake response can also be induced by lesions which involve only cell bodies. Finally, these results led us to conclude that the SA uses its cell bodies and afferent bodies and fibers for processing inputs mediating water intake and salt appetite and that the cells bodies of the SA are implicated in increased water intake.

The lateral preoptic area plays a dual role in the regulation of thirst in the rat.

Electrolyte lesion and ibotenic acid lesion of the lateral preoptic area (LPO) of the rat were used to study the participation of this area in drinking behavior. Drinking was induced by cellular dehydration, hypovolemia, hypotension, and water deprivation. The animals with electrolytic lesion of the LPO showed a significant reduction in water intake in response to cellular dehydration, hypotension, and deprivation. The animals with ibotenic acid lesion of the LPO increased the water consumption produced by subcutaneous (SC) injection of hypertonic saline. The amount of water intake after SC injection of polyethyleneglycol (PEG) or isoprenaline was similar in control and ibotenic acid-lesioned animals. The rats with ibotenic acid lesion of the LPO drank significantly more water than control animals. Fibers of passage may also influence the drinking response, and the LPO may have osmosensitive receptors that facilitate water intake in connection with other areas of the central nervous system (CNS) that are implicated in drinking behavior.

Influence of the subfornical organ on water intake induced by septal lesion.

Rats bearing lesions in the septal area (SA), or in the subfornical organ (SFO) or simultaneously in both regions were submitted to various thirst-eliciting procedures. The rats with hyperdipsia induced by lesion of the SA drank more water than either normal rats or SFO-lesioned animals under the same thirst-eliciting or angiotensin-liberating stimuli (polyethyleneglycol, isoproterenol, water deprivation and ligation of the inferior vena cava). The overdrinking elicited by SA lesions was blocked after SFO lesions. Neither hypovolemia, nor hypotension or water deprivation could elicit increased water intake in SFO-lesioned animals even after destruction of the SA. Animals with SFO lesions did not show increase of the water intake after cellular dehydration. The results obtained suggest that the SFO acts as the main structure in the regulation of water intake elicited by angiotensin with two opposite effects: one direct, facilitating water intake and the other indirect inhibiting the SA. The SA has an inhibitory effect on the SFO and on water intake.

Influence of the subfornical organ on water intake induced by septal lesion

Rats bearing lesions in the septal area (SA), or in the subfornical organ (SFO) or simultaneously in both regions were submitted to various thirst-eliciting procedures. The rats with hyperdipsia induced by lesion of the SA drank more water than either normal rats or SFO-lesioned animals under the same thirst-eliciting or angiotensin-liberating stimuli (polyethyleneglycol, isoproterenol, water deprivation and ligation of the inferior vena cava). The overdrinking elicited by SA lesions was blocked after SFO lesions. Neither hypovolemia, nor hypotension or water deprivation could elicit increased water intake in SFO-lesioned animals even after destruction of the SA. Animals with SFO lesions did not show increase of the water intake after cellular dehydration. The results obtained suggest that the SFO acts as the main structure in the regulation of water intake elicited by angiotensin with two opposite effects: one direct, facilitating water intake and the other indirect inhibiting the SA. The SA has an inhibitory effect on the SFO and on water intake.

Influence of the subfornical organ on water intake induced by septal lesion.

Rats bearing lesions in the septal area (SA), or in the subfornical organ (SFO) or simultaneously in both regions were submitted to various thirst-eliciting procedures. The rats with hyperdipsia induced by lesion of the SA drank more water than either normal rats or SFO-lesioned animals under the same thirst-eliciting or angiotensin-liberating stimuli (polyethyleneglycol, isoproterenol, water deprivation and ligation of the inferior vena cava). The overdrinking elicited by SA lesions was blocked after SFO lesions. Neither hypovolemia, nor hypotension or water deprivation could elicit increased water intake in SFO-lesioned animals even after destruction of the SA. Animals with SFO lesions did not show increase of the water intake after cellular dehydration. The results obtained suggest that the SFO acts as the main structure in the regulation of water intake elicited by angiotensin with two opposite effects: one direct, facilitating water intake and the other indirect inhibiting the SA. The SA has an inhibitory effect on the SFO and on water intake.