Effect of chronic oral administration of a low dose of captopril on sodium appetite of hypothyroid rats: Influence of aldosterone treatment

Rats rendered hypothyroid by treatment with methimazole develop an exaggerated sodium appetite. We investigated here the capacity of hypothyroid rats (N = 12 for each group) to respond to a low dose of captopril added to the ration, a paradigm which induces an increase in angiotensin II synthesis in cerebral areas that regulate sodium appetite by increasing the availability of circulating angiotensin I. In addition, we determined the influence of aldosterone in hypothyroid rats during the expression of spontaneous sodium appetite and after captopril treatment. Captopril significantly increased (P<0.05) the daily intake of 1.8 percent NaCl (in ml/100 g body weight) in hypothyroid rats after 36 days of methimazole administration (day 36: 9.2 + or - 0.7 vs day 32: 2.8 + or - 0.6 ml, on the 4th day after captopril treatment). After the discontinuation of captopril treatment, daily 1.8 percent NaCl intake reached values ranging from 10.0 + or - 0.9 to 13.9 ± 1.0 ml, 48 to 60 days after treatment with methimazole. Aldosterone treatment significantly reduced (P<0.05) saline intake before (7.3 + or - 1.6 vs day 0, 14.4 + or - 1.3 ml) and after captopril treatment. Our results demonstrate that, although hypothyroid rats develop a deficiency in the production of all components of the renin-angiotensin-aldosterone system, their capacity to synthesize angiotensin II at the cerebral level is preserved. The partial reversal of daily 1.8 percent NaCl intake during aldosterone treatment suggests that sodium retention reduces both spontaneous and captopril-induced salt appetite

Brain serotoninergic stimulation mreduces the water intake induced by systemic and central beta-adrenergic administration

This study was undertaken to determine if the stimulation of central serotoninergic receptors affects the thirst-inducing action of systemically or intracerebroventricularly (icv) injected isoproterenol. Male Wistar rats weighing 220-300 g were used in groups of 10-14 animals each. Normally hydrated rats implanted with a delay cannula into the third ventricle were injected icv with the 5HT1C/5HT2 agonist MK212 (50 nmol/2 ul) prior to administration of isoproterenol sc (330 ug/kg body weight) or icv (10 and 25 and 50 ug/2 ul). Icv injections of MK212 reduced the water intake induced by isoproterenol injected systemically (56%) and by the two lowest doses of isoproterenol injected icv (76 and 86%, respectively). The results suggest that the central serotoninergic system modulates the central beta-adrenergic system involved in water intake. Taken together with previous results mshowing that the activation of 5HT1C/5HT2 receptorspromotes a rfeduction of the dipsogenic response avoked by water deprivation or by icv injection of angiotensin II or carbachol, the present data suggest that the central serotoninergic system plays a ubiquitous role in thje modulation of water intake behavior

Effect of central administration of serotoninergic agonists on electrolyte excretion control

The participation of different central serotoninergic (5HT) receptors in the mediation of Na+ excretion (UNaV), K+ excretion (UKV) and urine output (UV) was evaluated. Male wistar rats weighing 220-280 g were used in each group of 9-18 animals. The rats were injected intracerebroventricularly (icv) with the 5 HT agonists MK212 (1.5, 15.0 and 30.0 *g), 8-OH-DPAT (5.0 and 15.0 *g) 5HT (2.5, 12.5 and 25.0 *g) and DOI (10.0 and 25.0 *g). At the lowest MK212 dose, UNaV was significantly reduced (0.18 ñ 0.04 *Eq/min vs 0.35 ñ 0.04 *Eq/min for saline) at 20 min. At the highest dose, MK212 provoked a significant increase in UNaV (0.60 ñ 0.06 *Eq/min vs 0.34 ñ 0.03 *Eq/min for saline) at 40 min UKV values were significantly modified only at the 1.5-*g dose (0.18 ñ 0.04 *Eq/min vs 0.04 *Eq/min for saline) at 20 min. Icv injection of 8-OH-DPAT provoked a significant reduction in UNaV (0.16 ñ 0.05 *Eq/min vs 0.35 ñ 0.03 Eq/min for saline) and UKV (0.15 ñ0.05 *Eq/min vs 0.34 * ñ 0.02 *Eq?min for saline) at 40 min at both doses. Icv injection of 5HT at the highest dose provoked a signficant increase in UNaV (0.92 ñ 0.10 *Eq/min vs 0.33 ñ 0.04 *Eq/min for saline) and in UKV (0.55 ñ 0.08 *Eq/min vs 0.24 ñ 0.07 *Eq/min for saline) at 40 min. Icv administration of DOT caused a natriuretic response (0.69 ñ 0.12 *Eq/min vs 0.31 ñ 0.04 *Eq/min for saline) at 40 min, with no significant effect on UKV. All the 5HT agonists induced a rapid antidiuretic response (35 to 75% below control levels), which was notably more intense and longer lasting at the highest 8-OH-DPAT dose. The results appear to indicate the involvement of both receptor families (5HT2) in the expression of the antidiuretic response. The present evidence indicates an opposite participation of the different receptor families in elicing the antinatriuretic (5HT1) and natriuretic (5HT2) responses

Participation of the median raphe nucleus and central serotoninergic pathways in the control of water electrolyte excretion

1. The role of the median raphe nucleus (MRN) and of increased central serotonin (5HT) synthesis/release in the mediation of Na+ excretion (UNaV) and K+ excretion (UKV) and or urine output (UV) was evaluated for 120 min. 2. Male Wistar rats weighing 220-280g were used in each group of 12-13 animals. The rats implanted with a cannula in the MRN were injected with saline (0.5 µl) or with 5.0 and 15.0 ng/0.5 µl kainic acid (KA), an excitatory amino (EAA). Another group of rats was injected ip with 200 mg/Kg saline or tryptophan, the initial precursor of 5HT synthesis. 3. Injection of both kainic acid and tryptophan led to increased Na+ excretion, but the magnitude and time course were different for each treatment. Both KA doses were effective in increasing UNaV (0.061 ñ 0.08, mean ñ SEM, and 0.95 ñ 0.19 -Eq/min, respectively, vs 0.27 ñ 0.04 µEq/min for saline at 60 min). The effect on UKV was statistically significant with the 15.0 ng dose (0.44 ñ 0.05 µEq/min vs 0.25 ñ0.03 µEq/min for saline) at 20 min. 5. Tryptophan adminsitration caused an initial gradual increase in UNaV which became steady and significant after 60 min (1.02 ñ 0.15 µEq/min vs 0.36 ñ 0.06 µEq/min for saline), as well as an increase in UKV (0.58 ñ 0.06 µEq/min vs 0.26 ñ 0.04 µEq/min for saline) at 60 min and throught the remainder of the observation period. 6. KA-induced MRN stimulation and systemic tryptophan overload significantly increased UV at 60, 80 and 100 min (30 to 97% above control values). 7. These data show that kanic acid-mediated transmission at the MRN lellvel may play a modulatory role in hydromineral metabolism. The effects obtained after increased central availability of tryptophan suggest that the excretory response is associated with an increase in 5HT synthesis/release and with an increase in central transmission. 8. We conclude that the data obtained from CA-induced MRN stimulation and systemic tryptophan overload may possibly reflect an increased 5HT synaptic transmission at sites and efferent mechanisms that remain to be elucidated

Effects of central epinephrine synthesis inhibition on stress-induced prolactin secretion in male rats

1. The present study was designed to examine the role of central epinephrine pathways in the control of stress-induced prolactin secretion in male adulto Wistar rats. 2. Intracerebroventricular adminsitration of two epinephrine synthesis inhibitors, SKF64139 (5 and 10 µg/rat) and LY 134046 (10 and 20 µg/rat), 6 h before the onset of immobilization stress blocked prolactin secretion in a dose-dependent manner. Prolactin values before stress were about 4.0 ng/ml and increased to almost 50 ng/ml in the control group. SKF 64139 injection in the higher dose (10 µg/rat) induced a complete blockade of the stress-induced prolactin release, whereas partial blockade was observed after the higher dose (20 µg/rat) of LY 134046. 3.Salbutamol pretreatment (10 µg/rat) completely restored stress-induced prolactin secretion in animals receiving a central injection of both epinephrine synthesis inhibitors under the same conditions as described above. 4. It is suggested that epinephrine pathways in the brain play an important role in the control of prolactin release occuring during immobilization stress

Drinking behavior in thyroidectomized rats: effects of central cholinergic stimulation and of water deprivation

Normally hydrated tytoidectomized (TX) rats stimulated intracerebroventricular with carbachol and delydrated TX rats drank significantly smaller volumes of water than their respective controls. This suggests lower central sensitivity to thirst and to drinking behavior induced by both cholinergic activation and extracellular fluid depletion. Dehydrated TX rats excreted a significantly larger urinary volume than the controls, suggesting the existence of changes in the renal mechanisms of water retention. Such changes could be related to a reduction in vasopressin binding sites

Thyroidectiomy reduces stress-induced prolactin secretion in rats. Participation of brain serotonergic systems

Plasma prolactin levels were measusred in thyroidectomized and sham-operated rats under immobilization stress. thyroidectomy significantly reduced prolactin secretion during stress. The pretreatment of thyroidectomized rats with 6-chloro-2[1-piperazinyl]-pyrazine (MK 212), a serotinin agonist that easily penetrates the blood-brain barrier, reversed the reduction in stress-induced prolactin release in the thyroidectomized group

Desipramine blocks stress-induced prolactin release in rats: role of central beta-2 adrenoceptors

The present study was designed to examine the relationship between beta-adrenoceptors and the enhanced, sustained prolactin secretion induced by immobilization stress in rats. Chronic administration of desipramine (15 mg kg**-1 day**-1, intraperitoneally) for 7 days, a procedure that desensitizes central beta-adrenoceptors, partially inhibits stress-induced prolactin release. Intracerebroventricular adminsitration of the beta-2 adrenoceptor agonist salbutamol (1 microng/rat) to rats pretreated with desipramine for 7 days, 15 min before immobilization, significantly relieved the inhibition by desipramine 5 and 10 min after the initiation of stress but the effect was not demonstrable after 20 and 40 min. We conclude that beta-2 adrenoceptors play a role in the control prolactin release in response to stress

Central serotonergic modulation of drinking behavior induced by water deprivation: effect of a serotonergic agonist (MK-212) administered intracerebroventricularly

The present study was carried out to evaluate the participation of the serotonergic system (5-HT) in the modulation of the drinking response induced by water deprivation. Male Wistar rats implanted with a cannula in the 3rd ventricle were injected with the 5-HT1C/5-HT2 agonist 6-chloro-2-[1-piperazinyl]-pyrazine (MK-212) at doses of 0.5, 5, 25, 50 and 125 nmol/2 µl. MK-212 induced a significant reduction (p < ou = 0.05) in water intake over a period of 300 min. This result indicates that the central 5-HT system plays an important role, probably at the level of the periventricular hypothalamus, in the modulation of drinking behavior induced by water deprivation

Central serotonergic modulation of drinking behavior induced by angiotensin II and carbachol in normally hydrated rats: effect of intracerebroventricular injection of MK-212

The objective of the present study was to evaluate the role of the central erotonergic (5-HT) system in the modulation of drinking behavior induced angiotensin II (Ang II) and carbachol. Male Wistar rats implanted with a delay cannula in the 3 rd ventricle were injected with the 5-HT1C/5-HT2 agonist 6-chloro-2-[1-piperazinyl]-pyrazine (MK-212) (50 nmol/2 µl) before receiving an intracerebro-ventricular (icv) injection of Ang II or carbachol (100 ng/2 µl). MK-212 induced a significant reduction in the drinking response evoked by Ang II or carbachol which was more marked in the case of the cholinergic agonist. The results obtained suggest that thirst and water intake produced by angiotensinergic or cholinergic activation are modulated by the action of 5-HT, possibly at the level of the periventricular hypothalamus

Participation of the serotonergic system in the regulation of water and electrolyte balance

To determine the possible participation of the serotonergic (5-Ht system in the regulation of water and electrolyte balance, rats were submitted to two sessions of water overloading and the 5-HT agonist MK 212 was administered intracerebroventricularly (icv) in 1.0 micronl 20 min after the second session. Urine volume and sodium and potassium excretion were measured over a priod of 120 min. Microinjection of MK-212 (1 microng/animal) caused a significant reduction (24 to 57%; mean, 43%) in natriuresis throghout the experimental period, and the administration of 10 microng/animal caused a 26-41% reduction (mean, 33%) in kaliuresis. At 20 microng/ animal, MK-212 did not change any of the parameters investigated. No significant change in urine volume was detected after any of the reatments used