W. A. Saad

Involvement of the Central Nervous System in the Salivary Secretion Induced by Pilocarpine in Rats

The effect in rats of an anteroventral third ventricle (AV3V) electrolytic lesion on salivary secretion induced by intraperitoneal (i.p.) or intracerebroventricular (i.c.v.) injection of a cholinergic agonist (pilocarpine) was investigated. Sham- or AV3V-lesioned rats anesthetized with urethane and with a stainless steel cannula implanted into the lateral ventricle (LV) were used. The amount of salivary secretion was studied over a seven-minute period after i.c.v. or i.p. injection of pilocarpine. In sham-operated rats, i.p. injection of pilocarpine (1 mg/kg b.w.) (after 6 h, 2, 7, and 15 days) produced salivary secretion (486 ± 21, 778 ± 85, 630 ± 50, and 560 ± 55 mg/7 min, respectively). This effect was reduced 6 h, 2, and 7 days after an AV3V lesion (142 ± 22, 113 ± 32, and 290 ± 62 mg/7 min, respectively), but not 15 days after an AV3V lesion (516 ± 19 mg/7 min). I.c.v. injection of pilocarpine (120 μg in 1 μL), in sham-operated rats after 6 h, 2, 7, and 15 days also produced salivary secretion (443 ± 20, 417 ± 81, 496 ± 14, and 427 ± 47 mg/7 min, respectively). The effects of i.c.v. pilocarpine were also reduced 6 h, 2, and 7 days after an AV3V lesion (143 ± 19, 273 ± 14, and 322 ± 17 mg/7 min, respectively), but not after 15 days (450 ± 28 mg/7 min). The results demonstrate that the central nervous system, and particularly the AV3V region, is important for the effect of pilocarpine on salivary secretion in rats. Moreover, they suggest that activation of central pathways may play an important part in the salivary secretion to peripheral pilocarpine in rats.

Natriuresis, kaliuresis and diuresis in the rat following microinjections of carbachol into the septal area

The effects of intraseptal injection of carbachol on natriuresis, kaliuresis and diuresis has been studied in conscious, unrestrained water-loaded male rats. Urinary sodium and potassium excretion increased following injections into the septal area. The intensity of the natriuresis and kaliuresis was dose-related. An antidiuretic effect was also observed. The Na+/K/ ratio increased with increasing doses of carbachol, indicating that the rise in urinary sodium exceeded that of potassium. Systematic mapping of the septal area yielded about the same results for all sites, excepting a zone located in the anterior-dorsal part of the medial nucleus which appeared more sensitive. The natriuretic effect of intraseptal carbachol in adrenalectomized rats demonstrated the secondary role played by the adrenals. Contrariwise the decrease of the natriuretic effect observed either in hypophysectomized rats or in rats bearing a median eminence lesion receiving intraseptal carbachol showed the important participation of these structures in urinary Na+ excretion. Adrenalectomy or median eminence lesions did not modify the kaliuretic response while hypophysectomy produced a transitory diminution. This fact favours the hypothesis of different mechanisms involved in Na+ and K+ excretion following intraseptal carbachol. These results leave open the question as to mechanism of action but suggest a possible role of the pituitary in mediating the responses. Also, the possibility of a role played by hemodynamic shifts is suggested.

Central nitrergic system regulation of neuroendocrine secretion, fluid intake and blood pressure induced by angiotensin-II

BackgroundNitric oxide (NO) synthesis has been described in several circumventricular and hypothalamic structures in the central nervous system that are implicated in mediating central angiotensin-II (ANG-II) actions during water deprivation and hypovolemia. Neuroendocrine and cardiovascular responses, drinking behavior, and urinary excretions were examined following central angiotensinergic stimulation in awake freely-moving rats pretreated with intracerebroventricular injections of Nω-nitro-L-arginine methyl ester (L-NAME, 40 μg), an inhibitor of NO synthase, and L-arginine (20 ug), a precursor of NO.ResultsInjections of L-NAME or ANG-II produced an increase in plasma vasopressin (VP), oxytocin (OT) and atrial natriuretic peptide (ANP) levels, an increase in water and sodium intake, mean arterial blood pressure and sodium excretion, and a reduction of urinary volume. L-NAME pretreatment enhanced the ANG-II response, while L-arginine attenuated VP and OT release, thirst, appetite for sodium, antidiuresis, and natriuresis, as well as pressor responses induced by ANG-II.Discussion and conclusionThus, the central nitrergic system participates in the angiotensinergic responses evoked by water deprivation and hypovolemia to refrain neurohypophysial secretion, hydromineral balance, and blood pressure homeostasis.

Interaction between areas of the central nervous system in the control of water intake and arterial pressure in rats

Water intake induced by injection of 0.2 M‐NaCl into the lateral preoptic area was increased by the injection of angiotensin II into the subfornical organ of rats. The injection of hypertonic saline solution into the subfornical organ increased water intake. However, the increase was lower than when the solution was injected into the lateral preoptic area. The injection of 4 micrograms angiotensin II into the lateral preoptic area further augmented this effect. Injection of angiotensin II into the subfornical organ caused a rise in blood pressure which preceded the thirst‐inducing effect. The injection of 0.2 M‐NaCl into the subfornical organ caused no changes in blood pressure, whereas the injection of angiotensin II into the lateral preoptic area caused some increase. Dehydration of the lateral preoptic area by means of 0.2 M‐NaCl in combination with intravenous infusion of angiotensin II caused a summation of effects in terms of the water intake, without changing cardiovascular alterations induced by the infusion of angiotensin II. A summation of effects in the water intake, but not in blood pressure, was also observed when 0.5 M‐NaCl was infused intravenously in combination with the injection of angiotensin II into subfornical organ and into the lateral preoptic area. The results indicate that there are interactions between the subfornical organ and lateral preoptic area in the regulation of cardiovascular and thirst mechanisms.

Effects of noradrenergic stimulation of the medial and lateral hypothalamus on cardiovascular responses.

Summary Microinjections of noradrenaline into the medial hypothalamus of anaesthetized normotensive rats elicited hypotensive and hypertensive effects. Noradrenergic stimulation of the dorsomedial nucleus of the hypothalamus caused a drop in arterial pressure and heart rate, which was abolished by previous injection of phentolamine but not by previous injection of propranolol. Noradrenaline injected into the ventromedial nucleus caused an increase in blood pressure and heart rate, which was blocked by propranolol but not by phentolamine. Microinjection of noradrenaline into the lateral hypothalamic area elicited tachycardia and a hypertensive response, both abolished by phentolamine, but not by propranolol.

Natriuresis induced by cholinergic stimulation of the locus coeruleus in the rat

Carbachol injected into the locus coeruleus (LC) induced a dose-dependent natriuresis in the rat. This natriuresis was maintained above control levels during the 120 min of urine sampling. Seizures and arterial blood pressure increase were also observed but they disappeared within 20 min after carbachol injection. Natriuresis was not obtained with either injections of carbachol outside the LC or with hypertonic solutions injected into the LC. Injection of atropine into the LC blocked the natriuresis induced by carbachol. In summary, our data show that carbachol induces natriuresis by an action on muscarinic receptors located in the LC region.

NOVEL EVIDENCE THAT BETA ADRENOCEPTORS OF THE MEDIAL SEPTAL AREA REGULATE BLOOD PRESSURE AND ELECTROLYTE BALANCE

We investigated the participation of the beta-adrenoceptors of the septa area (SA) in sodium and potassium excretion and urine flow. The alterations in arterial pressure and some renal functions were also investigated. The injection of 2.10(-9) to 16.10(-9) M of isoproterenol, through a cannula permanently implanted into the SA produced a significant dose-dependent decrease in urinary Na+ and K+ excretion and urinary flow. Pretreatment with 16.10(-9) M butoxamine antagonized the effect of 4.10(-9) M isoproterenol but pretreatment with 16.10(-9) M practolol did not abolish the effect of isoproterenol. The beta 2-agonist terbutaline and salbutamol (4.10(-9) M when injected intraseptally also caused a decrease in urine flow and in renal Na+ and K+ excretion. After injection of isoproterenol or salbutamol (4.10(-9) M) into the SA, the arterial pressure, glomerular, filtration rate (GFR) and filtered Na+ were reduced while Na+ fractional reabsorption was increased. The results indicate that the beta 2-adrenoceptors of the SA play a role in the decrease of Na+, K+ and urine flow and this effect may be due to a drop in GFR and filtered Na+ and to the rise in tubular Na+ reabsorption.

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 V1a, V2, and V1a/V2 (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 V1a antagonist decreased, and the V2 antagonist and Conivaptan (a V1a/V2 antagonist) increased, the urinary flow induced by AVP. Administration of AVP increased sodium excretion. Pretreatment with V2 or V1a antagonists decreased, and Conivaptan abolished, the sodium excretion induced by AVP. These results indicate that the V1a and V2 receptors of the MSA are important in the central regulation of urine and sodium excretion.

Effects of α and β adrenolytic agents on the changes in arterial pressure induced by intrahypothalamic injection of carbachol and nicotine

Abstract In order to elucidade some aspects of cholinergic and adrenergic interaction in the dorsomedial nucleus of the hypothalamus and its effect on systemic arterial pressure, carbachol and nicotine were injected into this area alone or preceded by regitine and propranolol. Both carbachol and nicotine induced hypotensive effects in normotensive anesthetized rats. Previous application of 20, 40, 80 and 160 nmol propranolol did not alter the hypotension induced, but doses of 20, 40 and 80 nmol regitine gradually attenuated the hypotensive effects of carbachol and nicotine.