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.

Effect of cholinergic and adrenergic stimulation of the subfornical organ on water intake

Cholinergic and adrenergic agonists and antagonists were injected directly into the subfornical organ (SFO), via implanted cannulae, and the volume of water ingested was recorded over a period of 1 hour after injection. Application of 2 nmol carbachol caused intense water intake in 100% of the animals (8.78±0.61 ml), with a very short intake latency. When the 2 nmol carbachol dose was preceded by increased doses of atropine, a progressive reduction in water intake was observed, with complete blockage of the thirst-inducing response to carbachol at the 20 nmol dose level with atropine. Followed by several doses of hexamethonium, the water intake caused by application of 2 nmol carbachol was reduced, although the response was not totally blocked. Injection of 80 nmol of nicotine had a significant thirst-inducing inducing effect in 50% of the animals studied (1.06±0.18 ml) and increase in water intake was further reduced by application of increased doses of hexamethonium. Raising the dose levels of noradrenaline into th SFO caused an increase in water intake although to a lesser degree than was observed after carbachol injection. When the 40 nmol dose of noradrenaline was preceded by increased doses of propranolol (5 to 40 nmol), there was a gradual reduction in water intake, with total blockage at the 40 nmol dose. Application of phentolamine in doses of 10 to 80 nmol caused no reduction in water intake after 40 nmol of noradrenaline. Application of isoproterenol at doses from 20 to 160 nmol into the SFO caused a dosedependent increase in water intake which was blocked by previous applications of propranolol. These results support the hypothesis that the water intake caused by chemical stimulation of the SFO is mainly due to muscarinic cholinergic receptors, although the influence of nicotinic receptors or participation of adrenergic mediation should not be ruled out. © 1984.

Effects of unilateral decortication on β-adrenergic receptors in the remaining cortex and in the hypothalamus of female rats

Many experiments have been performed to evaluate the physiological role of catecholaminergic mechanisms of gonadotropin release. The purpose of the present study was to determine the concentration of β-adrenoreceptors in the remaining (right) cerebral cortex and in right and left hypothalamic halves of hemi-decorticated female rats which exhibited elevated plasma gonadotropin levels as observed previously. The density of β-receptors was measured using a high-affinity β-adrenergic ligand, iodocyanopindolol (ICYP). Scatchard estimates were obtained for maximum binding (B(max) fmol/mg of tissues) from pooled cerebral cortical and hypothalamic tissue of animals under several experimental conditions after hemi-decortication and sham operation. There was an increase in β-adrenoreceptor density in the remaining (right) cerebral cortex at all times examined in hemi-decorticate in comparison with the sham-operated animals (7 days, +10.9%; 21 days, +8.4%; 90 days, +22%; and 90 days plus ovariectomy, +34.8%). The number of β-adrenoreceptors in the right hypothalamic half in hemi-decorticates decreased at 21 days (-42.20%) and then increased at 90 days (+76.63%) and 90 days plus ovariectomy (+51.75%) when compared with the left hypothalamic half. At the same time there were no significant changes in the sham-operated animals when comparing the receptor density in the right and left hypothalamic halves, respectively. Thus, our results suggest a direct adrenergic pathway by which the left cortex can influence the right cortex and a crossed pathway to the contralateral hypothalamus changing adrenergic activity which can alter the β-adrenergic receptor binding capacity in the hypothalamus.

Study of the contraction induced by norepinephrine and clonidine in the isolated guinea-pig ileum

Norepinephrine (NE) and clonidine produce a phasic, dose-dependent contraction of the isolated guinea-pig terminal ileum. The effect of NE was blocked by prazosin which produced a parallel rightward shift of the concentration-effect curve to NE, with a significant depression of maximum effects. Yohimbine and indomethacin noncompetitively blocked, whereas practolol potentiated, the contractile effect of NE. The contractile effect of clonidine was not antagonized by indomethacin or atropine. These results suggest that the isolated guinea-pig terminal ileum has excitatory receptors sensitive to clonidine stimulation and excitatory alpha receptors sensitive to blockade by prazosin, and that the activation of the latter may be related to the activation of endogenous prostaglandin synthesis.

Doença pulmonar obstrutiva crônica

Chronic obstructive pulmonary disease (COPD) is an extremely common disorder that all primary care physicians should be able to manage. In this review we will define the entities incorporated in COPD and will present various aspects of the diagnoses and treatment. We could not cover every aspect of this broad topic even providing a detailed review of those areas but some facets of therapy like smoking cessation, drug therapy, oxygen therapy, nutrition, and respiratory rehabilitation will be described.

HIPERTENSAO ARTERIAL NA CRIANCA

The objective of this report was to summarily review the concept and the prevalence of arterial hypertension in children, its peculiarities and the difficulties in measuring of blood pressure at this age. Considerations of clinical picture, diagnosis, laboratory and drug-induced test (Captopril) were discussed. The authors presented various therapies utilized in hypertension and hypertensive crisis.

Agents that inhibit histamine release: A review

It is well known that histamine is found in high concentration in mast cell granules(1). The histamine content of these granules may be released to the extracellular space if an appropriate stimulus is provided(2). Besides histamine, other preformed active substances like enzymes, chemotatic factors and proteoglycans, as well as newly generated mediators like eicosanoids, platelet activating factor and adenosine are released during the secretion process of mast cells(3). The activation of mast cell degranulation has been associated with a number of pathologic disorders, most frequently, diseases derived from the atopic state(4). It is now evident that mast cells are the primary effector cells in the early reaction in both allergic and non-allergic asthma(5,6), although some authors doubt that the late reaction of asthma is a mast cell dependent event(6). Other studies point towards basophils as cellular elements involved in the secondary phase of inflammation in allergic diseases(7). Secretion would depend on a histamine releasing factor, and on the presence of IgE on the basophil's surface(8). There is also evidence suggesting involvement of mast cells in some non-allergic inflammatory processes like arthritis(9). The pharmacological management of these diseases basically consists in the use of methylxantines, beta 2-adrenergic agonists, glucocorticoids, sodium cromoglycate-like drugs, anticholinergic and antihistaminic H 1 antagonists(10). Their therapeutic effects include bronchodilatation, receptor and physiological antagonism, prevention of inflammatory responses induced by secondary cells, and finally, inhibition of mast cell activation(11). This review is concerned with compounds having inhibitory action on mast cell activation, and their possible importance on the pathophysiology of mast cell-related diseases.

On a possible dual role for central noradrenaline in the control of hydromineral fluid intake

Noradrenaline (NOR) is a neurotransmitter presenl in the central nervous system which is related to the control of ingestive behavior of food and fluids. We describe here the relationship between NOR and intake of water and NaCl solution, fluids that are essential for a normal body fluid electrolytic balance. Central NOR has an inhibitory effect on fluid intake, but it either induces or not alterations in food intake. Several ways of inducing water intake, such as water deprivation, meal-associated water intake, administration of angiotensinergic, cholinergic or beta-adrenergic agonists, or administration of hyperosmotic solutions, are inhibited by alpha-adrenergic agonists. Need-induced sodium intake by sodium-depleted animals is also inhibited by alpha-adrenergic agonists. NOR can also facilitate fluid intake. Water intake is elicited by NOR and the integrity of central noradrenergic systems is necessary for a normal expression of water or salt intake in dehydrated animals. The angiotensinergic component of either behavior apparently depends on a central noradrenergic system. NOR probably facililates fluid intake by acting on postsynaptic receptors, but we do not know how it inhibits fluid infake. The inhibitory and facilitatory effects of NOR on ingestive behavior suggest a dual role for this neurotransmitter in the control of hydromineral fluid intake.

TRATAMENTO DA HIPERTENSAO ARTERIAL LEVE E MODERADA COM FOSINOPRIL. COMPARACAO DE EFEITOS ADVERSOS COM OUTROS ANTI-HIPERTENSIVOS

Purpose - To evaluate the adverse reactions of fosinopril with other antihypertensives used as monotherapy. Methods - Out-patients (n = 2,568) with diagnostic of mild to moderate hypertension, diastolic blood pressure (DBP) 95-115 mmHg, with no antihypertensive treatment for 15 days, were included to treatment initially with fosinopril (F) 10mg, once daily, for six weeks. After this period, patients with DBP >95mmHg had the dosage, once daily, increased to 20 mg, while the others were maintained with the same dosage for six more weeks. Adverse reactions of 822 patients treated as monotherapy were grouped as absent, musculoskeletal, cardiovascular, cough, gastrointestinal, neurological, genital-urinary dysfunctions and dermatological and compared with 1,568 with F. Monotherapy consist in α-methyldopa (100 patients); β-blocker (129); calcium blocker (106); diuretic (394); and another ACE inhibitors (93). Results - At the end of the period without treatment, the blood pressure (BP), 165 ± 16/105 ± 7 mmHg decreased significantly at 6(th) week to 144 ± 15/91 ± 9 mmHg (p < 0.05 vs week 0) with further lowering to 139 ± 13/86 ± 7 mmHg till the end of 12(th) week. BP response (DBP ≤90 mmHg) was obtained in 89% of the patients with F. Absence of adverse reactions were ≥70% in patients with F compared to other drugs. Conclusion - Fosinopril has demonstrated therapeutic efficacy and less adverse reactions compared to antihypertensives used previously as monotherapy.

α-Adrenoceptor-mediated prejunctional effects of chloroethylclonidine in the canine saphenous vein

The present study was undertaken to look for the effect of chloroethylclonidine (CEC) on prejunctional alpha-2 autoreceptors of the canine saphenous vein. The effect was tested on tritium overflow evoked by electrical stimulation from tissues preloaded with 0.2 μM 3H- norepinephrine. Yohimbine (3-300 nM) and CEC (1-125 μM) increased and UK- 14,304 reduced the overflow of tritium evoked by 300 pulses (1 Hz). The maximal increase of tritium overflow caused by yohimbine was much higher than that caused by CEC: 3.82 and 1.74 times, respectively. CEC (5 μM) abolished both the inhibition caused by UK-14,304 and the enhancement of tritium overflow caused by yohimbine. However, when CEC was added after yohimbine, it reduced the electrically evoked overflow of tritium, the maximal effect being a reduction of tritium overflow by 35%. Prazosin (1-100 nM) did not change either the inhibitory effect of UK-14,304 or the facilitatory effect of CEC. These results suggest that CEC acts on two different subtypes of prejunctional alpha-2 autoreceptors; on one of them it acts as an antagonist and increases the electrically evoked overflow of tritium (and inhibits both the effect of UK-14,304 and yohimbine); on the other it acts as an agonist and reduces the electrically evoked overflow of tritium. Alternatively, one can admit that CEC is able to inhibit alpha-2 autoreceptors, which causes an increase of the transmitter release, and to activate a nonadrenergic inhibitory receptor thus causing a reduction of the transmitter release.

The comparative efficacy of yohimbine and atipamezole to treat amitraz intoxication in dogs

This study compared the efficacy of yohimbine with atipamezole, a new α2-adrenergic antagonist, to treat canine amitraz intoxication. Thirty dogs were divided equally into 3 groups (A, AY, and AA). Group A received 2.5% amitraz iv at 1 mg/kg; Group AY received the same dose of amitraz followed 30 min later by 0.1 mg/kg (2 mg/mL) yohimbine iv; and Group AA received the same dose of amitraz followed 30 min later by 0.2 mg/kg (5 mg/mL) atipamezole iv. Temperature, heart rate, respiratory frequency, mean arterial pressure, degree of sedation, mean time of tranquilization and diameter of pupils were monitored for 360 min. Sedation, logs of reflexes, hypothermia bradycardia, hypotension, bradypnea and mydriasis were observed in Group A, with 3rd eyelid prolapse, increased diuresis and vomiting in some animals. Yohimbine reversed all alterations induced by amitraz, but induced significant cardiorespiratory effects such as tachycardia and tachypnea. Atipamezole was a useful antagonist for amitraz, with less cardiorespiratory effects, suggesting its potential role as an alternative treatment of amitraz intoxication in dogs.