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. (C) 2000 Elsevier B.V. B.V. All rights reserved.

Sino-aortic denervation causes right atrial beta adrenoceptor down-regulation

Rat isolated right atria obtained 1 wk after sinoaortic denervation were less sensitive to the chronotropic actions of beta-agonists than were tissues obtained from animals that underwent sham surgery or no surgery at all. The potencies, but not the maximal responses for two high efficacy agonists, norepinephrine and isoproterenol, were reduced about 3- to 4-fold. Sinoaortic denervation (SAD) caused about a 3-fold decrease in potency and about a 60% decrease in maximal response for a low efficacy agonist, prenalterol. The changes in the actions of these agonists occurred in the absence of any changes in the subtype of beta receptor mediating the chronotropic response. The results of analyses of the data for prenalterol showed that SAD caused a decrease in the operational efficacy of this agonist without any changes in its K-D value for beta-1 adrenoceptors. SAD had no effect on the responses of the tissue to blockade of uptake 1 and uptake 2, suggesting no compensatory changes in the removal processes caused the decreased potency. The results of radioligand binding assays showed that SAD caused a decrease in the maximal binding of I-125-cyanopindolol without altering its K-D. Also, the results of competition binding assays confirmed the lack of effect of SAD on the K-D for prenalterol. The SAD-induced changes in the actions of agonists acting at right atrial beta-1 receptors were caused by a down-regulation of beta-1 adrenoceptors, which probably occurred in response to SAD-induced increases in sympathetic tone.

Central moxonidine on water and NaCl intake

In this study we investigated: (a) the effects of intracerebroventricular (i.c.v.) injections of moxonidine (an alpha(2)-adrenergic and imidazoline receptor agonist) on the ingestion of water and NaCl induced by 24 h of water deprivation; (b) the effects of i.c.v. injection of moxonidine on central angiotensin II (ANG II)- and carbachol-induced water intake; (c) the effects of the pre-treatment with i.c.v, idazoxan (an alpha(2)-adrenergic and imidazoline receptor antagonist) and RX 821002 (a selective alpha(2)-adrenergic antagonist) on the antidipsogenic action of central moxonidine. Male Holtzman rats had stainless steel cannulas implanted in the lateral cerebral ventricle. Intracerebroventricular injection of moxonidine (5 and 20 nmol/1 mu l) reduced the ingestion of 1.5% NaCl solution (4.1 +/- 1.1 and 2.9 +/- 2.5 ml/2 h, respectively vs. control = 7.4 +/- 2.1 ml/2 h) and water intake (2.0 +/- 0.6 and 0.3 +/- 0.2 ml/h, respectively vs. control = 13.0 +/- 1.4 ml/h) induced by water deprivation, Intracerebroventricular moxonidine (5 nmol/1 mu l) also reduced i.c.v. ANG Ii-induced water intake (2.8 +/- 0.9 vs. control = 7.9 +/- 1.7 ml/1 h) and i.c.v. moxonidine (10 and 20 nmol/1 mu l) reduced i.c.v. carbachol-induced water intake (4.3 +/- 1.7 and 2.1 +/- 0.9, respectively vs. control = 9.2 +/- 1.0 ml/1 h). The pre-treatment with i.c.v. idazoxan (40 to 320 nmol/1 mu l) abolished the inhibitory effect of i.c.v, moxonidine on carbachol-induced water intake. Intracerebroventricular idazoxan (320 nmol/1 mu l) partially reduced the inhibitory effect of moxonidine on water deprivation-induced water intake and produced only a tendency to reduce the antidipsogenic effect of moxonidine on ANG Ii-induced water intake. RX 821002 (80 and 160 nmol/1 mu l) completely abolished the antidipsogenic action of moxonidine on ANG Ii-induced water intake. The results show that central injections c: moxonidine strongly inhibit water and NaCl ingestion. They also suggest the involvement of central alpha(2)-adrenergic receptors in the antidipsogenic action of moxonidine. (C) 1999 Elsevier B.V.

IMPORTANCE OF CONTROLLING THE STRESS IN THE VALIDATION OF BIOLOGICAL RESULTS

The stress syndrome includes ample phenomena, characterized by complex neuroendocrinological alterations. Such alterations, in the long run, give rise to important modifications in reply of different organs and tissues to diverse agonists, specially sympathicommentic. These alterations, at least partially, are part of an ''adjustment mechanism'' of the tissues. Thus this possibility of obtaining altered responses in function of stress leads to the need of special care in the prevention and control of stressogenic stimuli in the process of research. Taking cave of preventing stressogenic stimuli, it becomes possible to determine a profile of trustworthy replies, considered as standard From such reply standards, toe can know more clearly what is a ''normal'' response or what is a response ''altered'' by some factor, specially stress.

Atypical beta-adrenoceptor subtypes mediate relaxations of rabbit corpus cavernosum

This study was performed to characterize the beta-adrenoceptor population in rabbit isolated corpus cavernosum (RbCC) by using nonselective and selective beta-adrenoceptor agonists and antagonists in functional assays. Metaproterenol, ritodrine, fenoterol, and 8-hydroxy-5-[(1R)-1-hydroxy-2-[N-[(1R)-2-(rho-methoxy-phenyl)1-methylethyl] amino] ethyl] carbostyril (TA 2005) (3-100 nmol each) dose dependently relaxed the RbCC preparations. These relaxations were markedly reduced by N-omega-nitro-L-arginine methyl ester (L-NAME; 10 muM) and 1H-[1,2,4]-oxadiazolo-[4,3,-a]quinoxalin-1-one (ODQ) (10 muM), whereas the adenylyl cyclase inhibitor SQ 22,536 [9-(2-tetrahydrofuryl)adenine] (10 muM) had no effect. In contrast, neither L-NAME nor ODQ affected the isoproterenol-induced RbCC relaxations, but SQ 22,536 abolished this response. Sildenafil (1 muM) significantly potentiated the relaxations induced by beta(2)-agonists without affecting the isoproterenol-evoked relaxations. Rolipram (10 muM) enhanced the relaxations elicited by isoproterenol but had no effect on those induced by the selective beta(2) agonists. Propranolol and (+/-)-1-[2,3-(dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanolhydrochloride (ICI 118,551) determined a rightward shift in the concentration-response curves to isoproterenol in a noncompetitive manner with a reduction of maximum response at the highest antagonist concentration, with the slope values significantly different from unity. Propranolol and ICI 118,551 had no effect on the relaxations elicited by fenoterol, TA 2005, metaproterenol, and ritodrine. Atenolol and 1-[2-((3-carbamoyl-4-hydroxy)phenoxy) ethylamino]-3-[4-(1-methyl-4-trifluoromethyl-2-imidazolyl)-phenoxy]2-propanol methanesulfonate (CGP 20712A) (0.1-10 muM) failed to affect the relaxations induced by all tested beta-adrenoceptor agonists. Our study revealed the existence of two atypical beta-adrenoceptors in the rabbit erectile tissue. Isoproterenol relaxes the rabbit cavernosal tissue by activating atypical beta-adrenoceptors coupled to adenylyl cyclase pathway, whereas the selective beta2-adrenoceptor agonists relax the RbCC tissue through another atypical beta-adrenoceptor subtype coupled to nitric oxide release from the sinusoidal endothelium.

Implication of the 5-HT(2A) and 5-HT(2C) (but not 5HT(1A)) receptors located within the periaqueductal gray in the elevated plus-maze test-retest paradigm in mice

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Ionotropic Glutamate Receptors in Hypothalamic Paraventricular and Supraoptic Nuclei Mediate Vasopressin and Oxytocin Release in Unanesthetized Rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Evaluation of Vmax as an index of myocardial contractility during afterload and preload elevations

In order to test if the maximal velocity of shortening (V(max)TP) reflects the level of inotropism and is affected by preload and afterload, the behavior of this index was compared in two groups of anesthetized, atropinized dogs when preload and afterload were raised with an angiotensin II infusion. In seven dogs (group I), the arterial pressure elevation was allowed to inhibit reflectively the sympathetic tone and depress contractility. In eleven dogs (group II), the adrenergic activity was abolished by previous administration of reserpine. In group I, there was a significant decrease in V(max)TP during the angiotensin infusion. In group II, there was no significant change in the value of this index when the drug was infused. In six animals of this group, a further increase of arterial pressure was induced, but the values of V(max)TP remained similar to control. These results suggest that this index reflects the inotropic state of the myocardium and does not suffer significantly from the influence of preload and afterload elevations within our experimental limits.

Influência da oclusão bilateral das artérias carótidas comuns sobre a atividade vagal

The effects of carotid occlusion on parasympathetic activity were studied in anesthetized dogs submitted to beta adrenergic blockade. Modifications of the heart rate, before and after administration of atropine, were utilized for assessment of vagal changes. When vagal activity was intact there was elevation of the heart rate. After parasympathetic blockade carotid occlusion did not cause heart rate modifications. The data suggest that carotid occlusion produced vagal inhibition.

Efeitos do fentanil, droperidol e inoval sobre função renal e eletrólitos (sódio e potássio)

The influence of Fentanyl, Droperidol and Innovar on renal function and electrolytes (sodium and potassium) were studied on 18 dogs. Fentanyl disturbs kidney function and decreases plasmatic potassium. Droperidol and Innovar do not disturb the main renal function but decrease plasmatic potassium. The results obtained point out the importance of associate employment of Fentamyl and Droperidol, since the latter seems to establish the renal disorders occasioned by Fentanyl, probably owing to its adrenergic α blocking action.

Supersensitivity of the isolated guinea-pig vas deferens induced by a toxic fraction of scorpion venom (Tityus serrulatus)

1. Tityustoxin (TsTx), a toxic fraction of Tityus serrulatus venom, was studied on the isolated guinea-pig vas deferens. It increased significantly the maximal response of the preparation to both norepinephrine and acetylcholine and decreased the effective median dose of norepinephrine. 2. The effect of TsTx on norepinephrine median dose was unchanged when atropinized or pharmacologically 'denervated' preparations were used but was abolished when both procedures were associated. 3. Atropinization of pharmacologically denervated muscles almost never modify the TsTx-induced increase in the maximal response to norepinephrine. 4. On denervated or phentolamine-treated muscles TsTx-induced increase in the maximal response to acetylcholine was abolished. 5. It was concluded that toxin predominantly induces adrenergic postsynaptic supersensitivity. 6. Of minor significance, it also induces presynaptic cholinergic and adrenergic supersensitivity. 7. Comparison of these results with those of crude venom indicates that TsTx effects may result from the sum of the effects of subcomponents not demonstrated by the chemical procedures here utilized.