effect of high-fructose intake on the vasopressor response to angiotensin ii and adrenergic agonists in Sprague-Dawley rats

Effect of losartan was assessed on systemic haemodynamic responses to angiotensin II [Ang II] and adrenergic agonists in the model of high-fructose-fed rat. Twenty-four Sprague-Dawley [SD] rats were fed for 8 weeks either 20% fructose solution [FFR] or tap water [C] ad libitum. FFR or C group received losartan [10mg/kg/day p.o.] for 1 week at the end of feeding period [FFR-L and L] respectively, then the vasopressor responses to Ang II, noradrenaline [NA], phenylephrine [PE] and methoxamine [ME] were determined. The responses [%] to NA, PE, ME and Ang II in FFR were lower [p<0.05] than C [FFR vs. C; 22 +/- 2 vs. 32 +/- 2, 30 +/- 3 vs. 40 +/- 3, 9 +/- 1 vs. 13 +/- 1, 10 +/- 1 vs. 17 +/- 1] respectively. L group had blunted [p<0.05] responses to NA, PE, ME and Ang II compared to C [L vs. C; 26 +/- 2 vs. 32 +/- 2, 30 +/- 3 vs. 40 +/- 3, 7 +/- 0.7 vs. 13 +/- 1, 5 +/- 0.4 vs. 17 +/- 1] respectively. FFR-L group had aggravated [p<0.05] response to NA and ME, but blunted response to Ang II compared to FFR [FFR-L vs. FFR; 39 +/- 3 vs. 22 +/- 2, 11 +/- 1 vs. 9 +/- 1, 3 +/- 0.4 vs. 10 +/- 1] respectively. Fructose intake for 8 weeks results in smaller vasopressor response to adrenergic agonists and Ang II. Data also demonstrated an important role played by Ang II in the control of systemic haemodynamics in FFR and point to its interaction with adrenergic neurotransmission

Involvement of alpha1-adrenoceptors subtypes in the cardiac failure in spontaneously hypertensive rats

The function of kidney deteriorates during the development of cardiac failure because of changes in renal haemodynamics and neurohormonal activity. This study aimed to examine the alpha1 adrenoceptor subtypes involved in mediating adrenergically induced renal vasoconstriction in a rat model of cardiac failure and hypertension. Spontaneously hypertensive rats [SHR] were used in the study. Cardiac failure was induced by the combined treatment of caffeine [40mg/kg] and isoprenaline [5mg/kg] for seven days. On day eight, the rats were used for acute study. The left kidney was exposed and renal blood flow [RBF] was measured with the help of electromagnetic probe. The reduction in renal blood flow induced by electrical renal nerve stimulation, intrarenal bolus doses of noradrenaline, phenylephrine or methoxamine were determined before and after administration of amlodipine, 5-methylurapidil, chloroethylclonidine and BMY 7378. Data, means +/- s.e.m were compared with 2 way ANOVA followed by Bonferroni post hoc with the significance level of 5%. The results obtained indicated that the renal vasoconstrictor responses in this model were attenuated mainly by amlodipine, 5 methylurapidil and BMY7378 but not by chloroethylclonidine. Furthermore, administration of chloroethylclonidine did not show a significant reduction in methoxamine induced renal vasoconstriction in cardiac failure SHR. This supported the view that alpha 1A- adrenoceptors are involved in renal vasculature SHR regardless of its pathophysiological state. The findings from this study further suggested that besides the alpha 1A, the alpha ID- adrenoceptors contribute to the adrenergically induced renal vasoconstrictor responses in cardiac failure SHR

Time-dependent changes in the vasoconstrictor responses in diabetic rats

Disturbed vascular reactivity is one of the cardinal complications of diabetes mellitus [DM]. Several mechanisms have been postulated to explain changes in vascular responses associated with DM such as altered intracellular calcium levels responses to the alpha -adrenergic stimulant, methoxamine [MTX] and the calcium pump inhibitor, cyclopiazonic acid [CPA] were tested on the aorta of streptozotocin [STZ] diabetic rats 2, 8 and 16 weeks after induction of diabetes. Neither MTX-nor CPA-evoked vasoconstrictor responses were changed in the 2-weeks-diabetic rats. In contrast, both MTX and CPA-induced contractions were significantly [P < 0.05] increased in the 8-weeks diabetic tissues. Conversely, the maximal vasoconstrictor responses to both MTX and CPA were significantly [P <0.05] reduced in the 16-weeks diabetic tissues [P < 0.05]. The increased MTX-induced contractions 8-wekks after induction of diabetes, and the reduction of responses in corresponding tissues 16-weeks after diabetes induction were reversed in the presence of the voltage-dependent calcium channel blocker, nifedipine. Changes in MTX-evoked responses in the 16-week diabetic tissues were unaffected in the Ca[++] -free medium or by endothelial denudation. The data of the current study suggest that: 1] Contractile responses to MTX and CPA change with the development of diabetes. 2] Middle stages of diabetes may be associated with enhanced contractile responses to the alpha-adrenergic agonists and calcium pump inhibitors, whereas in late stages of diabetes attenuation of responses to the same vasoconstrictor agents may develop, 3] Changes of functional Ca[++] store size in the endoplasmic reticulum, and Ca[++] influx, mainly through voltage-dependent Ca[++] channels, may account for altered contractile responses to MTX and CPA in diabetic rats

The Effect of Isovolemic Hemodilution on the Autoregulation of Cerebral Blood Flow / 대한마취과학회지

BACKGROUND: Hemodilution may increase cerebral blood flow (CBF) but the mechanism(s) remain controversal. Autoregulation is easily modified or disturbed by several conditions. The aim of this study was to evaluate the effects of isovolemic hemodilution on the autoregulation of cerebral blood flow in a rabbit model. METHODS: Stepwise hemodilution was accomplished by incrementally removing whole blood from the animals in amounts of 8-12 ml and replacing this with an equal volume of 6% hetastarch in saline. This procedure was continued until the target content values of approximately Hct -18% were achieved. To evaluate the influence of pressure changes on CBF, mean arterial pressure (MAP) was increased from a baseline pressure (approximately 78 mmHg) to 145 mmHg by infusing methoxamine, and cerebral blood flow was measured at each MAP level using the hydrogen clearence method after MAP had been stabilized for 15 min. RESULTS: Stepwise hespen replacement caused a sudden drop of Hct from 37.4% to 18.5% and a simultaneously a significant increase in local CBF of 161% in the hemodilution group. Hemodilution significantly reduced CaO2 in the hemodilution group (9.45 +/- 1.7 ml O2/dl) versus the control group (18.34 +/- 1.3 ml O2/dl). However, despite these decrease in CaO2, calculated cerebral oxygen delivery (DO2) was as well maintained in the hemodilution group (22.47 +/- 7.28 ml O2/100 gm/min) as in the control group (24.14 +/- 8.67 ml O2/100 gm/min). MAP increases from 78 mmHg to 145 mmHg produced a significant increase in CBF from 122.4 +/- 32.8 ml/100 gm/min to 170.9 +/- 23.7 ml/100 gm/min in control group (39.6%) and from 218.4 +/- 75.6 ml/100 gm/min to 268.4 +/- 106.5 ml/100 gm/min in the hemodilution group (44.6%) (P<0.001). These CBF increases were not significantly different in the two groups. CONCLUSIONS: The present study demonstrates that in the normal brain the decrease in CaO2 caused by hemodilution is well compensated for by an increase CBF, and that oxygen transport to the brain is also well maintained during at a Hct value of 20%. Although the present study did not show the tight CBF control within the MAP range from 78 mmHg to 145 mmHg, hemodilution did not alter the response of the cerebral circulation to increased MAP.

Repeated intracerebral microinjections: efficacy in studying brain functions.

Injection of chemicals into the brain has been considered as an important technique to study various functions of the brain. In these studies, as a rule, only one bilateral injection is given in one animal. This study was undertaken to evaluate the quality of the body temperature data obtained after first and second injections of methoxamine and artificial cerebrospinal fluid into the medial preoptic area. Though there was quantitative decrease in the effects produced after the second injection of the drug, there was no significant change in the effects produced by the second injections of artificial cerebrospinal fluid, which was used as a vehicle. Results of this study support the earlier recommendation to perform only one injection in any of the brain sites for evaluating the effect of any drug. But the vehicle can be administered as a second injection, without compromising on the quality of data.

Prevention of spinal anaesthesia-induced hypotension in elderly: methoxamine or ephedrine

Two vasopressors were compared to reduce incidence of hypotension during spinal anaesthesia in elderly patients, methoxamine 10mg i.m. or ephedrine 10mg i.v. plus 20mg I.m, in terms of haemodynamic stability and requirement for additional vasopressors. Forty patients [aged 60-75yr] undergoing surgery of the lower body were allocated randomly into group M [n=20] and group E [n=20] the vasopressors were injected 10 min before induction of spinal anaesthesia. Rescue ephedrine 3-6 mg was given if systolic blood pressure [SAP] or mean arterial blood pressure [MAP] reduced more than 25% of the base line value. Patient and spinal characteristics were similar in the two groups. SAP and MAP increased initially form baseline until induction of spinal anaesthesia and then decreased for 25 min in both groups [not significant between groups]. Heart rate [HR] decreased from the baseline in group M [p<0.05] and was lower than in group E at all time form 4-70 min [p<0.01]. The incidence of hypotension of SAP and MAP was not significant between groups [SAP 25% vs 30% and MAP 20% vs 25%]. Requirements for rescue ephedrine [20% vs 25%] dose of rescue ephedrine given [4.8 vs 5.1mg] and time to onset of hypotension [9.8 vs 11.6 min] were similar in groups M and E. respectively. We conclude that methoxamine 10mg i.m. given 10 min before induction of spinal anaesthesia in normovolaemic elderly insignificantly reduce Incidence of subsequent SAP and MAP hypotension. requirements for rescue vasopressor therapy but has significant reduction of HR compared with ephedrine 10 mg i.v. plus 20mg i.m

Effects of hydralazine on cardiac responsiveness to adrenergic agonists in streptozotocin-induced diabetic rats.

The present investigation was undertaken to study the effects of hydralazine treatment (50 mg/kg/day, p.o.) on methoxamine and isoproterenol-induced responses in cardiac preparations of control and streptozotocin (STZ)-induced diabetic rats. Triiodothyronine (T3) and thyroxine (T4) levels were found to be significantly decreased in diabetic rats and this decrease was prevented by hydralazine treatment. Methoxamine and isoproterenol produced a dose-dependent positive chronotropic and positive inotropic effect in right and left atrium respectively. These responses to methoxamine were significantly increased, whereas, those to isoproterenol were significantly decreased in preparations obtained from diabetic rats. Hydralazine treatment did not alter the isoproterenol-induced chronotropic effect in right atrium. However, it prevented the diabetes-induced increase in responsiveness to methoxamine in this preparation. Hydralazine increased significantly the inotropic response to methoxamine and isoproterenol in left atrium of control and diabetic rats. Both the pD2 value and maximum response were increased. The studies indicates that hydralazine-induced alterations in the responsiveness to methoxamine could partly be due to its ability to prevent diabetes-induced hypothyroidism. The effects of hydralazine on isoproterenol-induced responses appear to be independent of hypothyroidism, and some post-receptor mechanisms and metabolic derangements might be responsible for this effect.

Propiedades antiadrenérgicas alfa de la espiroxatrina, un ligando de los receptores serotonérgicos 5-HT1A / Antiadrenergic properties of spiroxatrine

La espiroxatrina, un ligando 5-HT1A, tiene muy baja afinidad por los sitios de unión Ó1-adrenérgicos y una afinidad relativamente alta por los sitios Ó2. No obstante, estudios funcionales recientes indican que la espiroxatrina es un potente antagonista de los receptores adrenérgicos a1 que median la contracción de la aorta de rata in vitro. Tomando en consideración las notables diferencias en la interacción de los fármacos con los receptores adrenérgicos Ó presentes en los diferentes modelos experimentales, el presente estudio fue diseñado para analizar las propiedades antagonistas Ó-adrenérgicas de la espiroxatrina en la rata descerebrada y desmedulada montada para el registro de la presión arterial. La norepinefrina y los agonistas adrenérgicos Ó1 y Ó2 metoxamina y clonidina, respectivamente, produjeron incrementos de la presión arterial en forma dependiente de la dosis. La espiroxitrina (1 mg/kg, i.v.) produjo un desplazamiento significativo de las curvas dosis-respuesta a los tres agonistas. La magnitud de dicho desplazamiento fue similar en los tres casos. Los resultados presentes sugieren que, aunque la espiroxatrina presenta propiedades antiadrenérgicas Ó1 y Ó2 en el modelo in vivo utilizado en este estudio, su potencia antagonista no parece corresponder con la encontrada en la aorta de rata. La posible participación de subtipo del receptor adrenérgico Ó1 es discutida

Aspecto histológico das arteríolas intramiocárdicas, nas situaçöes da vasodilataçäo e vasoconstricçäo induzida por drogas / Histologic aspects of intramyocardial arterioles, during vasodilation and vasoconstriction induced by drugs

O aspecto histol[ogico das arteríolas intramiocárdicas do cäo, foi estudado em diferentes condiçöes hemodinâmicas, induzidas por drogas. A avaliaçäo das condiçöes hemodinâmicas foi feita pela medida das pressöes de átrio direito e aorta e pelo fluxo sangüíneo coronário obtido por fluxômetro eletromagnético. A avaliaçäo da motricidade arteriolar foi feita pela medida da relaçäo parede/luz dos vasos intramiocárdicos, em cortes histológicos corados pela HE. Os resultados revelaram uma relaçäo parede/luz de 1:1 para os casos controle, 0,3 para as situaçöes de vasodilataçäo e 1,5 para as condiçöes de vasoconstricçäo. Os autores sugerem que a expressäo histológica das arteríolas intramiocaárdicas, em condiçöes de vasodilataçäo e vasoconstricçäo, pode representar os limites da expressäo hemodinâmica da curva de autoregulaçäo circulatória coronariana

Contractile reactivity of the perfused mesenteric vascular bed from sinoaortic denervated rats to norepinephrine, methoxamine and verapamil

The contractile reactivity to noropinephrine, methoxamine, and verapamil of the perfused mesenteric vascular bed from sinoaortic denervated (SAD) and sham-operated (SO) rats was studied 3 to 30 days after surgery. A gradual but incomplete reduction of arterial hypertension was observed in SAD rats throughout the study. The norepinephrine-and methoxamine-induced dose-response curves were similar in both SAD and SO groups on day 3, but shifted to the left on days 7 and 15 and demonstrated a tendency to shift to the right at 30 days. Verapamil-induced vasodilation was similar in both groups. Enhanced mesenteric vascular responsiveness to endogenous catecholamines could contribute to the increased vascular resistance

Efeito inibidor de aminas simpatomiméticas nas respostas contráteis do duodeno de rato ao cálcio e ao bário / The inhibitory effect of sympathomimetics amines in the contractle responses of rat duodenum to calcium and barium

O duodeno de rato imerso em uma soluçäo de Tyrode sem cálcio responde com contraçöes equivalentes ao bário e ao cálcio. As respostas contráteis ao cálcio säo quantitativamente bloqueadas tanto por alfa como por beta simpatomiméticos. A açäo inibidora dos simpatomiméticos é reduzida pelos agentes simpatolíticos correspondentes e também pela efedrina, que näo possui atividade intrínseca. A açäo dos simpatomiméticos foi acentuadamente reduzida pela despolarizaçäo do duodeno com excesso de potássio. Os simpatolíticos fentolamina e propranolol têm efeito semelhante ao dos anestésicos locais, isto é, inibiçäo das contraçöes produzidas por bário tanto em soluçäo de Tyrode normal como com excesso de potássio; eles näo interferem com as respostas ao cálcio em condiçöes normais. Conclui-se que a despolarizaçäo do duodeno de rato rompe a interaçäo normal dos simpatomiméticos com os receptores adrenérgicos; a açäo das drogas na preparaçäo despolarizada é por uma interferência inespecífica à permeabilidade dos íons na membrana celular

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.

Studies on Bradycardiac Effect of Methoxamine in Rabbits / 대한마취과학회지

The bradycardiac and presor to intravenous and intraventricular methoxamine were examined in urethane-anesthetized rabbits 1) Intravenous methoxamine produced bradycardiac pressor responses. Atropine (2 mg/kg, i,v.) weakened but not abloished the bradycardiac effect. 2) The bradycardiac effect elicited by intravenous methoxamine was not affected by int-ravenous prazosin, rehimbiine, guanethidine and propranolol, butt was attenuated by intra venous chlorisondamine reserpine. 3) The pressor effect elioited by intravenous methoxamine was weakened by prazosin, but was scarcely affected, rather potentiated, by intraTenous yohimblne, guanethidine, chlorisondamine, propranolol and resperpine. 4) Intraventricular methoxamine produced pressor and bradycardiac responses. 5) The bradycardiac effect elicited by intraventricular methoxamine was net affected by intravenous atropine, prasosin and yohimbine. This was attenuated by intravenous guane- thidine, chlorisondamine, propranolol and reserpine, and by intraventricular atropine prazosin and propranolol, respectively. 6) The pressor effect elicited by intraventricular methoxamine was attenuated by intra- ventricular and intravenous prazosin. This was not affected by intravenous atropine, gua-nethidine, chlorisondamine, propranolol, reserpine and yohimbine, and by intraventricular atropine, prasosin and Propranolol, respectivelr. 7) From these results it was inferred that bradycardiac effect elicited by methoxamine was not an action through the mediation of aleph 1-adrenoceptors but was a result from non-specific actions on some brain receptors.

Diferentes efectos de la adrenalina sobre el músculo liso traqueal de Erythrocebus patas: predominio de los receptores adrenérgicos alfa / Diferent effects of adrenaline on the Erythrocebus patas tracheal smooth muscle: predominance of alpha-adrenergic receptors

Al comparar la reacción del músculo liso traqueal del cobayo a la adrenalina con la obtenida en la tráquea aislada del mono Erythrocebus patas (E. patas), se encontró que en este último la catecolamina producía contracciones repetidas de duración breve en lugar de la relajación ordinaria que induce en la tráquea del cobayo y de otras especies, incluyendo al hombre. En vista de esto se decidió estudiar el efecto de un agonista (metoxamina) y de un antagonista (zolertina) selectivos para los receptores adrenérgicos alfa sobre la cadena traqueal en ambas especies. La administración de metoxamina al baño de tejido aislado produjo contracción de las tráqueas de ambas especies relacionada con la concentración del agonista. Swin embargo, el músculo liso de Erythrocebus patas resultó ser claramente más sensible que el del cobayo al efecto contráctil de la metoxamina. El contacto previo de las preparaciones con zolertina produjo disminución en la magnitud de las reacciones a la metoxamina. Aunque este fenómeno se observó en las tráqueas de las dos especies, el desplazamiento de las curvas de dosis y respuesta de la metoxamina hacia la derecha ocurrió en el tejido del primate a concentraciones diez veces menores que en el caso del cobayo. Estos resultados sugieren que en el músculo liso traqueal de Erythrocebus patas existe un predominio de los receptores adrenérgicos alfa, lo cual si bien difiere del tejido humano normal parecería tener semejanza con lo que ocurre en el músculo liso traqueobronquial del paciente asmático

Influence of beta-adrenoceptor antagonists on spontaneous rate and on force of contraction of isolated rabbit atria.

The influence of beta-adrenoceptor antagonists on the spontaneous rate and on force of contraction of the myocardium was studied independently on spontaneously beating right and electrically driven isolated left atria of rabbit. On spontaneous rate, practolol had sympathomimetic effect only, N-isopropylmethoxamine (IMA), had both sympathomimetic as well as depressant effects, whereas alprenolol, procinolol, bunolol and H 35/25 had depressant effects only in higher concentrations. The order of potency was procinolol greater than bunolol greater than alprenolol greater than H 35/25 greater than and IMA. On the contractions of isolated left atria, all beta-adrenoceptor antagonists produced concentration-dependent depressant effect. In relation to procinolol, these agents were 5-125 times less potent for depressing the contractions of left atria by 15% and the order of beta-potency was procinolol greater than alprenolol greater than bunolol = H 35/25 greater than IMA greater than and practolol. The present results indicate that the depressant effects of beta-adrenoceptor antagonists on spontaneous rate of right atria and on contraction of isolated left atria are not related to each other.