Injection Of Norepinephrine Research Articles

Acute injections of corticosterone, norepinephrine and epinephrine retards food passage in the crop of chicks

The purpose of the present study was to clarify whether acute injection of stress-related hormones, corticosterone (CORT), norepinephrine (NE) and epinephrine (E) affect food passage in the crop of chicks (Gallus gallus). Subcutaneous (SQ) injection of CORT significantly retarded the food passage in the crop of chicks. Intraperitoneal (IP) injection of NE and E also significantly decreased the crop emptying rate. Additional experiments by using agonists of adrenergic receptors found that IP injection of phenylephrine and clonidine but not isoproterenol retarded the food passage in the crop of chicks. These results demonstrated that the effect of NE and E would be mediated by alpha-1-, alpha-2- rather than beta-adrenergic receptor. Finally, we found that injection of CORT, NE and E had no effect on the number of defecations while intracerebroventricular injection of corticotropin-releasing hormone and urocortin-3 significantly increased it. These results suggest that CORT, NE and E might affect the food passage in the upper digestive tract in chicks.

Intravenous tryptophan administration attenuates cortisol secretion induced by intracerebroventricular injection of noradrenaline.

This study was conducted to investigate the possibility of suppression of stress-induced cortisol (CORT) secretion by tryptophan (TRP) administration and to better understand its regulatory mechanisms by using a noradrenaline (NA) injection into the third ventricle (3V) as a stress model in cattle. A total of 25 Holstein steers with a cannula in the 3V were used. First, the increase in CORT secretion was observed following a NA injection into the 3V in a dose-dependent manner, verifying the appropriateness of this treatment as a stress model of CORT secretion (Experiment 1). The effect of prior-administration of TRP into peripheral blood with a dose that has been demonstrated to increase brain 5-hydroxytryptamine levels on the elevation of plasma CORT induced by NA or corticotropin-releasing hormone (CRH) was then examined (Experiment 2). The prior administration of TRP suppressed NA-induced, but not CRH-induced, CORT elevation. These results suggest that an increase in TRP absorption into peripheral blood could suppress the stress-induced CORT secretion in cattle via the attenuation of the stimulatory effect of NA on the hypothalamic CRH release.

The antithrombotic effect of RSNK in blood-stasis model rats

Ethnopharmacological relevanceReduction of Sheng-Nao-Kang decoction (RSNK), composed of Salvia miltiorrhiza Bge., Ligusticum chuanxiong Hort., Astragalus membranaceus (Fisch.) Bunge., Pueraria lobata (Willd.) Ohwi., Paeonia lactiflora Pall. and Panax notoginseng (Burk.) F. H. Chen., is a modified traditional Chinese medicinal formula of Sheng-Nao-Kang pill preparation, which has been investigated its protective effect on focal cerebral ischemia-reperfusion injury in rat in our previous report. Aim of the studyTo evaluate the antithrombotic effect of RSNK in blood stasis model rats and explore the potential mechanisms. Materials and methodsSubcutaneous injection of norepinephrine and bovine serum albumin combined with ice water bath was used to establish the acute blood stasis rat model. The anticoagulant activities were investigated by measuring activated partial thromboplastin time (APTT), thrombin time (TT), prothrombin time (PT), and the content of fibrinogen (FIB). Meanwhile, the levels of thromboxane A2 (TXA2), prostaglandins I2 (PGI2), endothelial nitric oxide synthase (eNOS) and endothelin (ET) were detected. ResultsThe treatment of RSNK was able to prolong APTT, TT and PT, and decrease FIB content obviously. Furthermore, it markedly suppressed TXB2 level and up-regulated 6-keto-PGF1α level of the blood-stasis model rats, accompanied with the decrease of T/K. The level of ET and TXA2 in plasma was down-regulated and the levels of eNOS in plasma and PGI2 in serum was up-regulated in RSNK-treated rats compared with model rats (P<0.05). ConclusionThe present study suggested that RSNK possessed remarkable antithrombotic property in blood stasis model rats induced by ice water bath and subcutaneous injection of norepinephrine and bovine serum albumin. This property could be associated with its anticoagulation activity, the regulation of active substances in vascular endothelium and maintaining the balance of TXA2 and PGI2.

Norepinephrine-Induced Adrenergic Activation Strikingly Increased the Atrial Fibrillation Duration through β1- and α1-Adrenergic Receptor-Mediated Signaling in Mice.

BackgroundAtrial fibrillation (AF) is the most common arrhythmias among old people. It causes serious long-term health problems affecting the quality of life. It has been suggested that the autonomic nervous system is involved in the onset and maintenance of AF in human. However, investigation of its pathogenesis and potential treatment has been hampered by the lack of suitable AF models in experimental animals.ObjectivesOur aim was to establish a long-lasting AF model in mice. We also investigated the role of adrenergic receptor (AR) subtypes, which may be involved in the onset and duration of AF.Methods and ResultsTrans-esophageal atrial burst pacing in mice could induce AF, as previously shown, but with only a short duration (29.0±8.1 sec). We found that adrenergic activation by intraperitoneal norepinephrine (NE) injection strikingly increased the AF duration. It increased the duration to more than 10 minutes, i.e., by more than 20-fold (656.2±104.8 sec; P<0.001). In this model, a prior injection of a specific β1-AR blocker metoprolol and an α1-AR blocker prazosin both significantly attenuated NE-induced elongation of AF. To further explore the mechanisms underlying these receptors’ effects on AF, we assessed the SR Ca2+ leak, a major trigger of AF, and consequent spontaneous SR Ca2+ release (SCR) in atrial myocytes. Consistent with the results of our in-vivo experiments, both metoprolol and prazosin significantly inhibited the NE-induced SR Ca2+ leak and SCR. These findings suggest that both β1-AR and α1-AR may play important roles in the development of AF.ConclusionsWe have established a long-lasting AF model in mice induced by adrenergic activation, which will be valuable in future AF study using experimental animals, such as transgenic mice. We also revealed the important role of β1- and α1-AR-mediated signaling in the development of AF through in-vivo and in-vitro experiments.

Sodium intake combining cholinergic activation and noradrenaline into the lateral parabrachial nucleus

The administration of cholinergic agonists like pilocarpine intraperitoneally (i.p.) or carbachol intracerebroventricularly (i.c.v.) induces water, but non significant hypertonic NaCl intake. These treatments also produce pressor responses, which may inhibit sodium intake. Noradrenaline (NOR) acting on α2-adrenoceptors in the lateral parabrachial nucleus (LPBN) deactivates inhibitory mechanisms increasing fluid depletion-induced sodium intake. In the present study, we investigated: (1) water and 1.8% NaCl intake in rats treated with pilocarpine i.p. or carbachol i.c.v. combined with NOR into the LPBN; (2) if inhibitory signals from cardiovascular receptors are blocked by NOR in the LPBN. Male Holtzman rats with stainless steel guide-cannulas implanted in the lateral ventricle and bilaterally in the LPBN were used. Bilateral injections of NOR (80nmol/0.2μl) into the LPBN decreased water intake (0.8±0.3, vs. saline (SAL): 2.9±0.3ml/180min) induced by pilocarpine (1mg/kg of body weight) i.p., without changing 1.8% NaCl intake (0.8±2.4, vs. SAL: 0.5±0.3ml/180min). Prazosin (1mg/kg of body weight) i.p. blocked pressor responses and increased water and 1.8% NaCl intake (6.3±1.7 and 14.7±3.5ml/180min, respectively) in rats treated with pilocarpine combined with NOR into the LPBN. Prazosin i.p. also increased 1.8% NaCl intake in rats treated with carbachol i.c.v combined with NOR into the LPBN. The results suggest that different signals inhibit sodium intake in rats treated with cholinergic agonists, among them those produced by increases of arterial pressure that are not efficiently deactivated by NOR acting in the LPBN.

Accessing to arteriovenous blood flow dynamics response using combined laser speckle contrast imaging and skin optical clearing.

Laser speckle contrast imaging (LSCI) shows a great potential for monitoring blood flow, but the spatial resolution suffers from the scattering of tissue. Here, we demonstrate the capability of a combination method of LSCI and skin optical clearing to describe in detail the dynamic response of cutaneous vasculature to vasoactive noradrenaline injection. Moreover, the superior resolution, contrast and sensitivity make it possible to rebuild arteries-veins separation and quantitatively assess the blood flow dynamical changes in terms of flow velocity and vascular diameter at single artery or vein level.

Aging-associated formaldehyde-induced norepinephrine deficiency contributes to age-related memory decline.

A norepinephrine (NE) deficiency has been observed in aged rats and in patients with Alzheimer’s disease and is thought to cause cognitive disorder. Which endogenous factor induces NE depletion, however, is largely unknown. In this study, we investigated the effects of aging-associated formaldehyde (FA) on the inactivation of NE in vitro and in vivo, and on memory behaviors in rodents. The results showed that age-related DNA demethylation led to hippocampal FA accumulation, and when this occurred, the hippocampal NE content was reduced in healthy male rats of different ages. Furthermore, biochemical analysis revealed that FA rapidly inactivated NE in vitro and that an intrahippocampal injection of FA markedly reduced hippocampal NE levels in healthy adult rats. Unexpectedly, an injection of FA (at a pathological level) or 6-hydroxydopamine (6-OHDA, a NE depletor) can mimic age-related NE deficiency, long-term potentiation (LTP) impairments, and spatial memory deficits in healthy adult rats. Conversely, an injection of NE reversed age-related deficits in both LTP and memory in aged rats. In agreement with the above results, the senescence-accelerated prone 8 (SAMP8) mice also exhibited a severe deficit in LTP and memory associated with a more severe NE deficiency and FA accumulation, when compared with the age-matched, senescence-resistant 1 (SAMR1) mice. Injection of resveratrol (a natural FA scavenger) or NE into SAMP8 mice reversed FA accumulation and NE deficiency and restored the magnitude of LTP and memory. Collectively, these findings suggest that accumulated FA is a critical endogenous factor for aging-associated NE depletion and cognitive decline.

Evaluation of the Cardiovascular Responses in Nicotinamide+Streptozotocin Diabetic Pithed Rats

In vitro studies have demonstrated that during diabetes a vascular dysfunction is observed. However, very few studies in vivo have confirmed these findings in the systemic vasculature. Thus, this study evaluated the vasopressor responses induced by sympathetic stimulation or by i.v. bolus injections of the agonists noradrenaline (α1/2), methoxamine (α1), UK 14,304 (α2), and the vasodepressor responses induced by acetylcholine and sodium nitroprusside in rats pretreated with: (i) nicotinamide + streptozotocin (NAD+STZ), (ii) saline + buffer, (iii) saline + streptozotocin (SAL+STZ); and (iv) nicotinamide + buffer. For this purpose, rats were treated with a single dose of nicotinamide (230 mg/kg, i.p.) or its vehicle (saline, 1 ml/kg) and 15 min after streptozotocin (65 mg/kg, i.p.) or its vehicle (citrate buffer, 1 ml/kg) was administered. 12 weeks latter, a tolerance glucose curve was determined after administration of glucose (1 g/kg, p.o.). Then, under anesthesia, the animals were pithed and prepared to measure blood pressure and heart rate. In animals treated with NAD+STZ intolerance to glucose was observed. Moreover, the vasopressor responses to sympathetic stimulation or noradrenaline, methoxamine and UK 14,304 remained unchanged. In contrast, in animals treated with SAL+STZ, the vasopressor responses induced by sympathetic stimulation or by methoxamine and UK 14,304 were blunted. Furthermore, the vasodepressor responses induced by acetylcholine, but not those induced by sodium nitroprusside, were significantly decreased in rats treated with NAD+STZ or SAL+STZ. These results suggest that in NAD‐STZ diabetic rats an impairment on the vasodepressor responses induced by acetylcholine was observed probably by an endothelial mechanism.

Altered urinary sodium excretion response after central cholinergic and adrenergic stimulation of adult spontaneously hypertensive rats.

In this study, we hypothesized that blunting of the natriuresis response to intracerebroventricularly (i.c.v.) microinjected cholinergic and adrenergic agonists is involved in the development of hypertension in spontaneously hypertensive rats (SHR). We evaluated the effect of i.c.v. injection of cholinergic and noradrenergic agonists, at increasing concentrations, and of muscarinic cholinergic and α1 and α2-adrenoceptor antagonists on blood pressure and urinary sodium handling in SHR, compared with age-matched Wistar Kyoto rats (WR). We confirmed that CCh and NE microinjected into the lateral ventricle (LV) of conscious rats leads to enhanced natriuresis. This response was associated with increased proximal and post-proximal sodium excretion accompanied by an unchanged rate of glomerular filtration. We showed that cholinergic-induced natriuresis in WR and SHR was attenuated by previous i.c.v. administration of atropine and was significantly lower in the hypertensive strain than in WR. In both groups the natriuretic effect of injection of noradrenaline into the LV was abolished by previous local injection of an α1-adrenoceptor antagonist (prazosin). Conversely, LV α2-adrenoceptor antagonist (yohimbine) administration potentiated the action of noradrenaline. The LV yohimbine pretreatment normalized urinary sodium excretion in SHR compared with age-matched WR. In conclusion, these are, as far as we are aware, the first results showing the importance of interaction of central cholinergic and/or noradrenergic receptors in the pathogenesis of spontaneous hypertension. These experiments also provide good evidence of the existence of a central adrenergic mechanism consisting of α1 and α2-adrenoceptors which works antagonistically on regulation of renal sodium excretion.

Calibration of baroreflex equilibrium diagram based on exogenous pressor agents in chronic heart failure rats.

A baroreflex equilibrium diagram describes the relation between input pressure and sympathetic nerve activity (SNA) and that between SNA and arterial pressure (AP). To calibrate the SNA axis (abscissa) of the baroreflex equilibrium diagram, the AP response to intravenous bolus injections of phenylephrine (0.2–50 μg/kg) or norepinephrine (NE, 0.02–5 μg/kg) was examined in normal control rats (NC, n = 9) and rats with chronic heart failure (CHF, n = 6). The maximum slope of the dose–effect curve was significantly smaller in the CHF group than in the NC group (57.3 ± 5.2 vs 80.9 ± 6.3 mmHg/decade for phenylephrine, 60.2 ± 7.8 vs 80.4 ± 5.9 mmHg/decade for NE; P < 0.01). The CHF/NC ratio of the maximum slope was used to calibrate SNA. While the calibrated baroreflex equilibrium diagram showed increased maximum SNA and operating-point SNA in CHF rats compared with NC rats, the magnitude of increase was smaller than that expected from the excess plasma NE concentration in CHF rats. Plasma NE concentration in the CHF group could be disproportionally high relative to SNA.

Modulation of Pain by Naloxone and a Possible Role of Neurotransmitters with Selective Lesion of Septal Nuclei

Septum occupies a strategic position in limbic system and has been implicated in variety of behaviors. Present study was designed to evaluate the role of medial septum in modulation of pain and explore the role of neurotransmitters. The present study was divided in two parts in first part the tail flick latencies were observed in rats with septal lesions and compared with sham operated ones. While in the second part, the effect of intraseptal injections of neurotransmitters and naloxone on tail flick latencies of cannulated rats was recorded after intraseptal lesions. It was observed that the septal lesions decrease pain threshold. The interaseptal injection of Acetylcholine (5 μg to 20 μg) and Naloxone (5 μg to 20 μg) increases pain threshold. While the Interaseptal injection of Noradrenaline and Scopolamine decreases pain threshold. The findings of the present study suggest that septum may be involved in modulation of pain. The neurotransmitters like Acetylcholine, Noradrenaline and opioid peptides may have an individual or collective role to play in the observed pain modulation.

Specific role of α2A - and α2B -, but not α2C -, adrenoceptor subtypes in the inhibition of the vasopressor sympathetic out-flow in diabetic pithed rats.

Several lines of evidence have shown an association of diabetes with a catecholamines' aberrant homeostasis involving a drastic change in the expression of adrenoceptors. This homeostatic alteration includes, among other things, atypical actions of α2 -adrenoceptor agonists within central and peripheral α2 -adrenoceptors (e.g. profound antinociceptive effects in diabetic subjects). Hence, this study investigated the pharmacological profile of the α2 -adrenoceptor subtypes that inhibit the vasopressor sympathetic out-flow in streptozotocin-pre-treated (diabetic) pithed rats. For this purpose, B-HT 933 (up to 30 μg/kg min) was used as a selective α2 -adrenoceptor agonist and rauwolscine as a non-selective α2A/2B/2C -adrenoceptor antagonist; in addition, BRL 44408, imiloxan and JP-1302 were used as subtype-selective α2A -, α2B - and α2C -adrenoceptor antagonists, respectively (all given i.v.). I.v. continuous infusions of B-HT 933 inhibited the vasopressor responses induced by electrical sympathetic stimulation without affecting those by i.v. bolus injections of noradrenaline in both normoglycaemic and diabetic rats. Interestingly, the ED50 for B-HT 933 in diabetic rats (25 μg/kg min) was almost 1-log unit greater than that in normoglycaemic rats (3 μg/kg.min). Moreover, the sympatho-inhibition induced by 10 μg/kg min B-HT 933 in diabetic rats was (i) abolished by 300 μg/kg rauwolscine or 100 and 300 μg/kg BRL 44408; (ii) partially blocked by 1000 μg/kg imiloxan; and (iii) unchanged by 1000 μg/kg JP-1302. Our findings, taken together, suggest that B-HT 933 has a less potent inhibitory effect on the sympathetic vasopressor responses in diabetic (compared to normoglycaemic) rats and that can probably be ascribed to a down-regulation of α2C -adrenoceptors.

Selection for high activity-related aerobic metabolism does not alter the capacity of non-shivering thermogenesis in bank voles

An intriguing question is how the capacity of non-shivering thermogenesis (NST)—a special mechanism supporting endothermic thermoregulation in mammals—is affected by selection for high exercise metabolism. It has been proposed that high NST could be a mechanism to compensate for a low basal production of heat. On the other hand, high basal or activity metabolism is associated with physiological characteristics such as high performance of the circulatory system, which are also required for achieving a high NST. Here we tested whether selection for high aerobic exercise performance, which correlates with an increased basal metabolic rate, led to a correlated evolution of maximum and facultative NST. Therefore, we measured the NST of bank voles, Myodes (= Clethrionomys) glareolus, from lines selected for 13–14 generations (n=46) for high aerobic metabolism achieved during swimming and from unselected, control lines (n=46). Open-flow respirometry was used to measure the rate of oxygen consumption (V·O2) in anesthetized bank voles injected with noradrenaline (NA). After adjusting for body mass, maximum NST (maximum V·O2 recorded after injection of NA) did not differ between the selected (2.38±0.08mLO2min−1) and control lines (2.36±0.08mLO2min−1; P=0.891). Facultative NST (= maximum NST minus resting metabolic rate of anesthetized animals) did not differ between the selected (1.49±0.07mLO2min−1) and control lines (1.50±0.07mLO2min−1; P=0.985), either. Therefore, our results suggest that NST capacity is not strongly linked to maximum activity-related aerobic metabolic rate.

Cerenkov Luminescence Imaging of Interscapular Brown Adipose Tissue

Brown adipose tissue (BAT), widely known as a “good fat” plays pivotal roles for thermogenesis in mammals. This special tissue is closely related to metabolism and energy expenditure, and its dysfunction is one important contributor for obesity and diabetes. Contrary to previous belief, recent PET/CT imaging studies indicated the BAT depots are still present in human adults. PET imaging clearly shows that BAT has considerably high uptake of 18F-FDG under certain conditions. In this video report, we demonstrate that Cerenkov luminescence imaging (CLI) with 18F-FDG can be used to optically image BAT in small animals. BAT activation is observed after intraperitoneal injection of norepinephrine (NE) and cold treatment, and depression of BAT is induced by long anesthesia. Using multiple-filter Cerenkov luminescence imaging, spectral unmixing and 3D imaging reconstruction are demonstrated. Our results suggest that CLI with 18F-FDG is a practical technique for imaging BAT in small animals, and this technique can be used as a cheap, fast, and alternative imaging tool for BAT research.

Cerenkov Luminescence Imaging of Interscapular Brown Adipose Tissue

Brown adipose tissue (BAT), widely known as a “good fat” plays pivotal roles for thermogenesis in mammals. This special tissue is closely related to metabolism and energy expenditure, and its dysfunction is one important contributor for obesity and diabetes. Contrary to previous belief, recent PET/CT imaging studies indicated the BAT depots are still present in human adults. PET imaging clearly shows that BAT has considerably high uptake of 18F-FDG under certain conditions. In this video report, we demonstrate that Cerenkov luminescence imaging (CLI) with 18F-FDG can be used to optically image BAT in small animals. BAT activation is observed after intraperitoneal injection of norepinephrine (NE) and cold treatment, and depression of BAT is induced by long anesthesia. Using multiple-filter Cerenkov luminescence imaging, spectral unmixing and 3D imaging reconstruction are demonstrated. Our results suggest that CLI with 18F-FDG is a practical technique for imaging BAT in small animals, and this technique can be used as a cheap, fast, and alternative imaging tool for BAT research.

Spinal mechanism of micturition reflex inhibition by naftopidil in rats

AimWe investigated the spinal mechanism through which naftopidil inhibits the micturition reflex by comparing the effects of noradrenaline and naftopidil in rats. MethodsThe following were investigated: the influence of oral naftopidil on plasma monoamine and amino acid levels, the distribution of oral 14C-naftopidil, the effects of intravenous (IV) or intrathecal (IT) injection of noradrenaline or naftopidil on isovolumetric bladder contractions, amino acid levels in the lumbosacral spinal cord after IT noradrenaline or naftopidil, and the effects of IT naftopidil and strychnine and/or bicuculline on isovolumetric bladder contractions. Key findingsOral naftopidil decreased the plasma adrenaline level, while it increased the serotonin and glycine levels. After oral administration, 14C-naftopidil was detected in the spinal cord and cerebrum, as well as in plasma and the prostate gland. When the bladder volume was below the threshold for isovolumetric reflex contractions, IV (0.1mg) or IT (0.1μg) noradrenaline evoked bladder contractions, but IV (1mg) or IT (0.01–1μg) naftopidil did not. When the bladder volume was above the threshold for isovolumetric reflex contractions, IV or IT noradrenaline transiently abolished bladder contractions. IT noradrenaline decreased the levels of glycine and gamma-aminobutyric acid (GABA) in the lumbosacral cord, while IT naftopidil increased the GABA level. IT strychnine and/or bicuculline blocked the inhibitory effect of IT naftopidil on bladder contractions. SignificanceNaftopidil inhibits the micturition reflex by blocking α1 receptors, as well as by the activation of serotonergic, glycinergic, and GABAergic neurons in the central nervous system.

Analgesia, enhancement of spinal morphine antinociception, and inhibition of tolerance by ultra-low dose of the α2A-adrenoceptor selective antagonist BRL44408

Ultra-low doses of non-selective α2-adrenoceptor antagonists augment acute spinal morphine antinociception and block morphine tolerance; however, the receptor involved in mediating these effects is currently unknown. Here, we used tail flick and paw pressure tests on the rat to investigate the acute analgesic and tolerance-inducing effects of spinal morphine and norepinephrine alone or in combination with an ultra-low dose of the α2A-adrenoceptor antagonist, BRL44408. We also assessed the potential antinociceptive effects of BRL44408 alone following spinal administration. A spinal dose of BRL44408, over 1000-fold lower than that required to inhibit clonidine-induced antinociception (1.65ng/10µL), significantly prolonged morphine and norepinephrine action in both nociception tests. Following repeated morphine or norepinephrine injections, 1.65ng BRL44408 attenuated both the decline of antinociceptive effect and increase in morphine ED50 values, responses indicative of acute morphine tolerance. BRL44408 administered alone produced a delayed antinociceptive effect unrelated to repeated nociceptive testing. This response was partially reduced by the α2-adrenoceptor antagonist atipamezole (10µg). Ultra-low dose BRL44408 was able to inhibit the loss of morphine- and norepinephrine-induced antinociceptive response, and prevent the loss of drug potency due to repeated agonist exposure. This implicates the spinal α2A-adrenoceptor subtype in the action of ultra-low dose α2-adrenoceptor antagonists on morphine and norepinephrine tolerance. The BRL44408-induced analgesia is partially dependent on its interaction with the α2-adrenoceptors. Thus, this agent class may be useful in pain therapy.

Renoprotective effects of gamma-aminobutyric acid on cisplatin-induced acute renal injury in rats.

To investigate the effect of gamma-aminobutyric acid (GABA) on acute renal injury (ARI), we used here a rat model of acute tubular necrosis induced by the anticancer drug cisplatin (CP). GABA was given orally (100 or 500mg/kg/day for ten consecutive days), and on the 6th day, some of the treated rats were also injected intraperitoneally with either saline or CP (6mg/kg). Four days after CP treatment, urine was collected from all rats, which were then anaesthetized for blood pressure and renal blood flow monitoring. This was followed by intravenous injection of norepinephrine for the assessment of renal vasoconstrictor responses. Thereafter, blood and kidneys were collected for measurement of several functional, biochemical and structural parameters. GABA treatment (at 500 but not 100mg/kg) significantly mitigated all the measured physiological and biochemical indices. Sections from saline- and GABA-treated rats showed apparently normal proximal tubules. However, kidneys of CP-treated rats had a moderate degree of necrosis. This was markedly lessened when CP was given simultaneously with GABA (500mg/kg). The concentration of platinum in the cortical tissues was not significantly altered by GABA treatment. The results suggested that GABA can ameliorate CP nephrotoxicity in rats. Pending further pharmacological and toxicological studies, GABA may be considered a potentially useful nephroprotective agent in CP-induced ARI.

Intravenous or Local Injections of Flavoxate in the Rostral Pontine Reticular Formation Inhibit Urinary Frequency Induced by Activation of Medial Frontal Lobe Neurons in Rats

The rostral pontine reticular formation has a strong inhibitory effect onmicturition by facilitating lumbosacral glycinergic neurons. We assessed the influence of the rostral pontine reticular formation on the micturition reflex after noradrenaline injection in the medial frontal lobe. We also examined the relation between the medial frontal lobe and the rostral pontine reticular formation. Continuous cystometry was performed in 28 female rats. After the interval between bladder contractions was shortened by noradrenaline injection in the medial frontal lobe we injected glutamate or flavoxate hydrochloride in the rostral pontine reticular formation or intravenously injected flavoxate or propiverine. The change in bladder activity was examined. Noradrenaline injection in the medial frontal lobe shortened the interval between bladder contractions. In contrast to the bladder contraction interval before and after noradrenaline injection in the medial frontal lobe, the interval was prolonged after noradrenaline injection when glutamate or flavoxate was injected in the rostral pontine reticular formation, or flavoxate was injected intravenously. Noradrenaline injection in the medial frontal lobe plus intravenous propiverine injection also prolonged the interval compared to that after noradrenaline injection alone. However, the interval after noradrenaline injection in the medial frontal lobe plus intravenous injection of propiverine was shorter than that before noradrenaline injection only. Medial frontal lobe neurons excited by noradrenaline may facilitate the micturition reflex via activation of inhibitory interneurons, which inhibit descending rostral pontine reticular formation neurons that innervate the lumbosacral glycinergic inhibitory neurons. Therefore, the mechanism of micturition reflex facilitation by the activation of medial frontal lobe neurons involves the rostral pontine reticular formation.

Evidence that chronic administration of 17β-oestradiol decreases the vasopressor responses to adrenergic system stimulation in streptozotocin-diabetic female rats

In vitro studies have indicated that 17β-oestradiol exerts beneficial effects on the cardiovascular system by activating the nitric oxide pathway. However, these effects have not been demonstrated in vivo in the systemic vasculature of rats made diabetic through streptozotocin induction. Therefore, the goal of this study was to determine the effect of 17β-oestradiol on vasopressor responses induced by sympathetic stimulation or i.v. injections of noradrenaline, methoxamine and B-HT 933 in sham-operated or ovariectomised, diabetic or non-diabetic female rats. Thus, rats were ovariectomised or sham-operated for this experiment. One week later, the animals were treated with streptozotocin (60mg/kg, i.p.) or its vehicle. Two weeks later, these rats were treated daily with 17β-oestradiol (10μg/kg, s.c.) or its vehicle for five weeks. Next, under anaesthesia, the animals were pithed and prepared for blood pressure and heart rate measurements. 17β-oestradiol failed to modify the vasopressor responses to (i) sympathetic stimulation, noradrenaline, methoxamine or B-HT 933 in sham-operated non-diabetic rats; (ii) sympathetic stimulation or B-HT 933 in sham-operated diabetic rats; (iii) noradrenaline or methoxamine in ovariectomised non-diabetic rats. In contrast, 17β-oestradiol significantly decreased the vasopressor responses to (i) noradrenaline and methoxamine in sham-operated diabetic rats; (ii) sympathetic stimulation or B-HT 933 in ovariectomised non-diabetic rats; and (iii) sympathetic stimulation, noradrenaline, methoxamine or B-HT 933 in ovariectomised diabetic rats. These results suggest that chronic administration of 17β-oestradiol decreases the vasopressor responses to adrenergic system stimulation in streptozotocin-induced diabetic rats. This report describes the first in vivo study reporting this effect of 17β-oestradiol in diabetes.