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.

Efecto de N-Nitro-L-Arginina sobre la contracción y relajación en músculo liso vascular / Effect of N-Nitro-L-Arginine on the concentration and relaxation of vascular smooth muscle

La contractilidad del músculo liso arterial esta regulado por la concentración de calcio libre intracelular y por la estimulación de receptores adrenérgicos (alpha 1 y alpha 2 (norepinefrina (NE), fenilefrina (PHE) y clonidina) inducen contracciones, aumentando la tensión vascular e incrementando la concentración de calcio intracelular. Esta respuesta aumenta en ausencia de endotelio. Por otro lado, la relajación de arterias aisladas inducidas por acetilcolina (ACh) es dependiente de endotelio y modulada por EDRF. Nosotros estudiamos el efecto de la preincubación N-nitro-L-arginina (L-NA) sobre la contracción alpha-adrenérgica inducida y la relajación inducida por ACh respectivamente en aorta torácica aislada de rata en comparación con el efecto producido por KCl 70mM, la cual es tomada como control. Los resultados muestran una diferencia significativa (p<0.001) en presencia de L-NA en la contracción producida por FE comparada a la ausencia de L-NA. En las tres concentraciones de ACh usadas, la presencia de L-NA indujo una relajación inferior al 20 por ciento. La ausencia de L-NA indujo 100 por ciento de relajación, retorno a la línea base. L-NA induce un aumento en la entrada de calcio através de canales modulados por receptor y porque la inhibición de la síntesis de EDRF produce un aumento de la tensión vascular. De la misma forma, la relajación se explicada por la liberación de EDRF estimulada por ACh, la cual es inhibida por L-NA. Considerando el endotelio vascular como un órgano paracrino, es importante e interesante estudiar la farmacomodulación de los efectos de NO/EDRF y por misma razón considerar al L-NA en el arsenal farmacológico.

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.

Vascular desensitisation--possible role of prostaglandins.

Prolonged exposure to noradrenaline (NA) brings about an increase in the release of prostaglandin (PG)-like material from rat aortic strip. The release is greater with oxymetazoline while methoxamine decreases it. These effects are blocked by yohimbine and prazosin respectively. Pretreatment with 6-OHDA or reserpine diminishes the release of PG-like material. Barium chloride, a non-specific spasmogen, does not affect the release significantly. It appears therefore that the source of PG-like material is presynaptic and that its release mechanism is linked to an alpha 2 (alpha 2) adrenoceptor. It is proposed that this release of PG-like material contributes to the development of desensitisation in vascular tissue.

Efecto de la estimulacion alpha 1 adrenergica sobre la relajacion miocardica / Effects of alpha 1 adrenergic stimulation on myocardial relaxation

El objetivo del presente trabajo fue el de estudiar los efectos que provoca la estimulación alfa1 adrenérgica sobre la relajación miocárdica. Para ello se realizaron experimentos en músculos papilares de gato contrayéndose isométricamente a frecuencia de 12/m y temperatura de 30§C. Se comparó el efecto que sobre la relajación miocárdica tiene un aumento en la contractilidad de aproximadamente 40 y 200 % producidos por fenilefrina (F) 10**-5 y 10**-4 M, respectivamente, en presencia de propranolol (10**-6M) y por aumento del Ca**2+ de 1.34 a 3.75 y 7.5 mM en presencia de propranolol o en animales prerreserpinizados. Un aumento en la máxima velocidad de contracción, +T, del 40% por F y por Ca**2+, aumentó proporcionalmente en ambos casos la máxima velocidad de relajación (-T), sin cambios en la relación +T/-T. F prolongó ligera pero significativamente el tiempo de relajación (Rt) y el tiempo hasta la mitad de la relajación (t 1/2), en tanto que Ca2+ no modificó estos parámetros. Para aumentos de +T del 200%, F y Ca2+ aumentaron proporcionalmente menos -T, con lo que +T/-T aumentó de 1.21 ñ 0.04 a 1.73 ñ 0.09 (48.3 ñ 9.5 %, F) y de 1.37 ñ 0.04 a 1.77 ñ 0.15 (31 ñ 12 %, Ca**2+). Rt aumentó significativamente tanto con Ca**2+ (21.5 ñ 8.8 %) como con F (24.2 ñ 2.68 %). t 1/2 en cambio aumentó sifnificativamente con F, de 215 + 11.4 ms a 282 ñ 12 ms (33 ñ 5.8 %) y no cambió con Ca**2+. El efecto de F fue revertido con prazosín. Los resultados indican que F en presencia de propranolon provoca...

Adrenergic receptors in the hypothalamus concerned with control of arterial blood pressure: elicited by electrical and chemical stimulation.

The study was made with the help of a chemitrode placed in various areas of the hypothalamus by the stereotaxic technique, for electrical and chemical stimulation (noradrenaline or isoprenaline) before and after microinjection of respective blockers (phenoxybenzamine or practalol). The results indicated the presence of both alpha and beta-adrenoreceptors in the anterior and dorsomedial hypothalamus producing a depressor response, and, the presence of alpha adrenoreceptors in the posterior and lateral hypothalamus producing a pressor response.