Participation of hepatic α/β-adrenoceptors and AT1 receptors in glucose release and portal hypertensive response induced by adrenaline or angiotensin II

It has been previously demonstrated that the hemodynamic effect induced by angiotensin II (AII) in the liver was completely abolished by losartan while glucose release was partially affected by losartan. Angiotensin II type 1 (AT1) and adrenergic (∝1- and β-) receptors (AR) belong to the G-proteins superfamily, which signaling promote glycogen breakdown and glucose release. Interactive relationship between AR and AT1-R was shown after blockade of these receptors with specific antagonists. The isolated perfused rat liver was used to study hemodynamic and metabolic responses induced by AII and adrenaline (Adr) in the presence of AT1 (losartan) and ∝1-AR and β-AR antagonists (prazosin and propranolol). All antagonists diminished the hemodynamic response induced by Adr. Losartan abolished hemodynamic response induced by AII, and AR antagonists had no effect when used alone. When combined, the antagonists caused a decrease in the hemodynamic response. The metabolic response induced by Adr was mainly mediated by ∝1-AR. A significant decrease in the hemodynamic response induced by Adr caused by losartan confirmed the participation of AT1-R. The metabolic response induced by AII was impaired by propranolol, indicating the participation of β-AR. When both ARs were blocked, the hemodynamic and metabolic responses were impaired in a cumulative effect. These results suggested that both ARs might be responsible for AII effects. This possible cross-talk between β-AR and AT1-R signaling in the hepatocytes has yet to be investigated and should be considered in the design of specific drugs.

The role of adrenergic receptor polymorphisms in heart failure

The main function of the cardiac adrenergic system is to regulate cardiac work both in physiologic and pathologic states. A better understanding of this system has permitted the elucidation of its role in the development and progression of heart failure. Regardless of the initial insult, depressed cardiac output results in sympathetic activation. Adrenergic receptors provide a limiting step to this activation and their sustained recruitment in chronic heart failure has proven to be deleterious to the failing heart. This concept has been confirmed by examining the effect of ß-blockers on the progression of heart failure. Studies of adrenergic receptor polymorphisms have recently focused on their impact on the adrenergic system regarding its adaptive mechanisms, susceptibilities and pharmacological responses. In this article, we review the function of the adrenergic system and its maladaptive responses in heart failure. Next, we discuss major adrenergic receptor polymorphisms and their consequences for heart failure risk, progression and prognosis. Finally, we discuss possible therapeutic implications resulting from the understanding of polymorphisms and the identification of individual genetic characteristics.

Intoxicación por amitraz: un agonista alfa 2 adrenérgico en un hombre de 21 años

Se describe el caso de un hombre de 21 años que ingirió triatox (amitraz) en un intento suicida. Se discuten las manifestaciones clínicas que producen la intoxicación por agonistas alfa 2 adrenérgicos, sus posibles complicaciones y su forma de manejo.

Sistema nervioso autónomo y estres gástrico, en ratas / Autonomic nervous system and gastric stress in rats

En grupos diferentes de ratas Wistar (n=10), se estudió el efecto fisiopatológico del sistema nervioso autónomo en el estrés gástrico, en el modelo experimental de estrés, por inmovilización e inmersión en agua a 15 grados Celsius durante 6 hs., en el que se tabuló el por ciento lesional macroscópica de la mucosa gástrica y en sangre se midió el cortisol, malatonina, nor-adrenalina, adrenalina, dopamina y serotonina. En estrés testigo se encontró un área necrótica gástrica de un 80 por ciento en sangre solo se halló aumento de nor-adrenalina y adrenalina. Se estudiaron fármacos en dosis dependientes, agonistas y antagonistas de los receptores Beta adrenérgicos, antagonistas alpha adrenérgicos postinápticos; colinérgicos y anticolinérgicos, de los receptores endorfínicos y de los GABA. Se encontró que Isoproterenal, Prazosim, Doxazosina, Tramadol y Vgabatrin dieron marcada protección de la mucosa gástrica en el estrés, con un área necrótica cercana al 0 por ciento (P<0.001); en contraste, Propanolol, Acetilcolina, Atropina, Naloxona y Flumazenil no se diferenciaron del estrés testigo (P>0.5). Todos los fármacos estudiados dieron similares aminas vasoactivas que el estrés testigo. Se concluyó que el sistema nervioso autónomo en su vinculado a sus receptores con incremento de la microcirculación esplácnica.

Alpha-adrenergic pathways in the lateral hypothalamus are important for the dipsogenic effect of carbachol injected into the medial septal area

We studied the effect of the Ó1-and Ó2-adrenergic receptors of the lateral hypothalamus (LH) on the control of water intake induced by injection of carbachol into the medial septal area (MSA) of adult male Holtzman rats (250-300g) implanted with chronic stainless steel cannulae into the LH and MSA. The volume of injection was always 1 µl and was injected over a period of 30-60 s. For control, 0.15MNaCl was used. Clonidine (20 nmol) but not phenylephrine (160 nmol) injected into the LH inhibited water intake induced by injection of carbachol (2 nmol) into the MSA, from 5.4 ñ 1.2ml/h to 0.3 ñ 0.1 and 3.0 ñ 0.9 ml/h, respectively (N=26). When we injected yohimbine (80nmol) + clonidine (20nmol) and prazosin (40nmol) + clonidine (20nmol) into the LH, water intake induced by injection of carbachol into the MSA was inhibited from 5.4 ñ 1.2 ml/h to 0.8 ñ 0.5 and 0.3 ñ 0.2 ml/h, respectively (N=19). Water intake induced by carbachol (2nmol) injected into the MSA was decreased by previous injection of yohimbine (80 nmol) + phenylephrine (160 nmol) and prazosin (40 nmol) + phenylephrine (160 nmol) from 5.4 ñ 1.2ml/h to 1.0 ñ 0.7 and 1.8 ml/h, respectively (N = 16). The cannula reached both the medial septal area in its medial portion and the lateral hypothalamus. It has been suggested that the different pathways for induction of drinking converge on a final common pathway. Thus, adrenergic stimulation of Ó2-adrenoceptors of LH can influence this final common pathway

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

1. Noradrenaline (NOR) is a neurotransmitter present 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. 2. 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. 3. 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 facilitates fluid intake by acting on postsynaptic receptors, but we do not know how it inhibits fluid intake. 4. The inhibitory and facilitatory effects of NOR on ingestive behavior suggest a dual role for this neurotransmitter in the control of hydromineral fluid intake.

Central alpha-adrenoceptor influence over the cardiovascular reflexes activated by veratrine.

Intravenous veratrine induced alterations in cardiovascular parameters in cats were used as a tool for assessing the influence of central alpha-adrenoceptors over reflex adjustments in the heart rate and blood pressure. Blockade of central alpha 2-adrenoceptors with idazoxan or yohimbine, inhibited, while their activation by clonidine, as also blockade of alpha 1-adrenoceptors, with prazosin, potentiated the veratrine induced bradycardia. The hypotensive effect was relatively unaltered by these treatments. Low doses of clonidine potentiated the veratrine-induced bradycardia. It appears that alpha 2-adrenoceptor mechanisms exert greater control over the reflex regulation of heart rate than over reflex control of blood pressure.