Effect of astragalus injection combined with beta-adrenoceptor antagonist on BNP,IL-1β,IL-6 and TNF-αlevels in senile heart failure patients / 中国生化药物杂志

Objective To investigate the effect of astragalus injection combined with beta-adrenoceptor antagonist on serum levels of brain natriuretic peptide ( BNP) , interleukin1β( IL-1β) , IL-6 and tumor necrosis factorα( TNF-α) in the treatment of elderly patients with heart failure. Methods 78 elderly patients with heart failure from April 2013 to April 2015 in department of cardiology of the second hospital of Yuhang district were selected and divided into control group and experimental group with 39 cases in each group.All patients received correction of the electrolyte and acid-base balance and other conventional treatment.The control group received carvedilol by oral, the experimental group received astragalus injection on the basis of control group, with a course of 30 days.The serum BNP,IL-1β,IL-6 and TNF-αlevels pre-and post-treatment in two groups were compared. Results Compared with pre-treatment, the serum IL-1β,IL-6,TNF-α,and BNP levels post-treatment in two groups were lower(P<0.05).Compared with the control group post-treatment, the IL-1β,IL-6,TNF-αand BNP levels in experimental group were lower(P <0.05).Conclusion Astragalus injection combined with beta-adrenoceptor antagonist could significantly improve the clinical sign of elderly patients with heart failure, the mechanism may be reducing the serum levels of IL-1β,IL-6,TNF-αand BNP.

Inhibitory effect of Suaeda asparagoides (Miq.) extract on the motility of rat gastric antrum is mediated by beta-adrenoceptor / 한국실험동물학회지

Suaeda asparagoides (Miq.) has long been used as a Korean folk herbal medicine for the treatment of functional gastrointestinal disorders. However, reports on its pharmacological activity on gastrointestinal motility are scarce. The present study investigated the effects of Suaeda asparagoides water fraction of the extract (SAWF) on antral motility in vitro. Muscle strips from rat gastric antrum were set up in an organ bath in a circular orientation. SAWF (100 microg/mL) inhibited the spontaneous contraction of antral circular muscle strips. These inhibitory effects were not significantly affected by tetrodotoxin (1 microM), N omega-Nitro-L-arginine methyl ester hydrochloride (100 microM), 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one (10 microM), ryanodine (10 microM) and phentolamine (10 microM). SAWF-induced inhibition was mostly restored by cyclopiazonic acid (10 microM). Furthermore, the beta-adrenergic receptor antagonist, propranolol (10 microM), abolished SAWF-induced inhibition. These results suggest that SAWF may exert its activity on gastrointestinal smooth muscle via a-adrenergic receptors and sarcoplasmic reticulum Ca2+ ATPase.

Effects of propofol on beta-adrenoceptor-mediated signal transduction in cardiac muscle; role of cAMP / 대한마취과학회지

BACKGROUND: Propofol may decrease myocardial contractility via actions on the beta-adrenoceptor-mediated signal transduction. The aim of this study was to evaluate the effect of propofol via beta-adrenoceptor-mediated signal transduction by measuring the tissue levels of cAMP (cyclic adenosine monophosphate). METHODS: The effects of propofol on beta-adrenoceptor mediated cascades were measured with cAMP concentrations, which were stimulated by agonists (l-isoproterenol, GTPgammaS, and forskolin) of each step of beta-adrenoceptor-mediated cascades. RESULTS: While the production of cAMP stimulated by isoproterenol, GTPgammaS, or forskolin are increased (P < 0.05), application of each concentration of propofol (0.1, 1, 10, 100 micrometer) did not alter the levels of cAMP. CONCLUSIONS: Considering that propofol did not alter the tissue cAMP levels when stimulated by isoproterenol, GTPgammaS, and forskolin, propofol appears to have no effect on the beta-adrenoceptor signaling pathway in guinea pig ventricular myocardium.

Changes in Awake Cystometry and Expression of Bladder beta-adrenoceptors after Partial Bladder Outlet Obstruction in Male Rats / 대한배뇨장애요실금학회지

PURPOSE: To explore possible changes in awake cystometry and expression of beta-adrenoceptors (ARs) as a cause for bladder dysfunction in a male rat model of partial bladder outlet obstruction (pBOO). MATERIALS AND METHODS: Awake cystometry was performed in rats with pBOO (16) and sham-operated rats (16), 8 weeks after the operation. The expression of mRNA and protein of beta-ARs was assessed by real-time PCR and western blot. RESULTS: The bladders with pBOO (1030mg) were increased compared to those in control rats (230mg). In the cystometric studies, the maximum intravesical pressure significantly increased in the pBOO group compared to control group rats (p=0.001). The time to reach maximal intravesical pressure during micturition in the pBOO group was significantly longer than the sham group (p=0.003). The frequency of non-void contraction in the pBOO group was significantly more than the sham group (p=0.006). The mRNA expressions of beta2- and 3-ARs were increased insignificantly in pBOO group compared to sham group. The data of pBOO group expressed as folds of corresponding expression in sham group were 1.28 and 1.46 respectively in beta2- and 3-ARs. Compared to the sham groups, the density of 60Kda protein band recognized by beta2-AR antibodies and the density of 45Kda protein band recognized by beta3-AR antibodies were higher in the bladder from pBOO group rats. CONCLUSION: PBOO of male rats increase the maximal intravesical pressure and contraction time during micturition and the frequency of non-void contraction as well as weight of bladder. The expression of beta2- and 3-ARs subtypes was increased insignificantly compared to sham operated group. This study demonstrates that the changes of cystometric or non-void contraction parameters in pBOO is one of the pathophysiologic processes potentially associated with the alterations of bladder beta-ARs.

The association between polymorphisms of beta-adrenoceptors and preeclampsia

PURPOSE: The beta-adrenoceptors are pharmacologically classified into beta1-, beta2- and beta3-adrenoceptor. The gene of each subtype has polymorphisms related to their function (beta1-adrenoceptor: Ser49Gly, beta2- adrenoceptor: Gln27Glu, beta3-adrenoceptor: Trp64Arg). The objectives of this study were to analyse the allelic and genotypic distribution of the representative polymorphism of beta-adrenoceptors in preeclampsia and to investigate whether combined genotype of beta-adrenoceptors may be associated with preeclampsia. METHODS: Blood samples were collected from a Korean population (159 preeclamptic pregnancies and 168 normotensive pregnancies). The beta1-, beta2- and beta3-adrenoceptor genotypes was determined using polymerase chain reaction-restriction fragment length polymorphism. RESULTS: There were no differences in allelic and genotypic distribution of beta1- and beta2-adrenoceptor polymorphisms between the two groups. However, the Arg allele of beta3-adrenoceptor polymorphism were more frequent in preecalmpsia than in controls (P<0.05, OR=1.57, 95% CI=1.01-2.46). Moreover, prevalence of genotype carrying heterozygote of beta3-adrenoceptor polymorphism was increased in preeclampsia compared with controls (P<0.05, OR 1.76, 95% CI 1.06-2.92). When combination of the three polymorphisms were evaluated, pregnancies with the particular combined genotype that is consisted of heterozygote of beta1-, beta3-adrenoceptor and wild homozygote of beta2-adrenoceptor (Ser/Gly, Gln/Gln, Trp/Arg), showed a significant increase in the risk of preeclampsia (P<0.05, OR=3.01, 95% CI 1.12-8.08). CONCLUSION: A particular combined genotype (Ser/Gly, Gln/Gln, Trp/Arg) of - adrenoceptors was associated with the risk of preeclampsia.

Electroacupuncture ameliorates experimental colitis induced by acetic acid in rat

The effect of electroacupuncture (EA) on experimental colitis was investigated in Sprague-Dawley rats. Colitis was induced by intracolonic instillation of 4% acetic acid. EA (2 Hz, 0.05 ms, 2 V for 20min) was applied to bilateral Hoku (LI-4) and Zusanli (ST-36) on 12 hrs and 36 hrs after induction of colitis. EA-treatment significantly reduced the macroscopic damage and the myeloperoxidase activity of colonic samples at 3 days post-induction of colitis. Colitic colon showed a decreased in vitro motility. However, colonic motility of EAtreated group was not significantly different from that of normal group. The anti-inflammatory effect of EA was not inhibited by a glucocorticoid receptor antagonist, RU-486, but suppressed by a beta-adrenoceptor antagonist, propranonol. These results suggest that EA-treatment has a beneficial effect on colitis, and its anti-inflammatory effect is mediated by beta-adrenoceptor activation but not by endogenous glucocorticoiddependent mechanism.

Contraction and Relaxation Responses of Isolated Rabbit Seminal Vesicle to Selective beta Subtypes-adrenoceptor Agonists and Antagonists / 대한비뇨기과학회지

PURPOSE: This study was aimed at investigating the role of betaadrenoceptor subtypes in mediating the relaxation and contraction of seminal vesicles in rabbits. MATERIALS AND METHODS: Relaxation or contractile responses of epithelium- removed muscle strips of a rabbit seminal vesicle, which were precontracted with 10-5M norepinephrine, to selective betasubtypes-adrenoceptor agonists were observed in an organ bath. The contractile responses induced by isoproterenol were also observed after application of selective antagonists. RESULTS: Isoproterenol showed a concentration-dependent contractile response, but the contractility was weaker than those with phenylephrine and norepinephrine. The betaselective-agonists(xamoterol for beta, clenbuterol for beta and BRL37344 for beta) alone evoked neither contraction nor relaxation. However, the beta- and beta-agonists inhibited the contraction of the precontracted strips with 10-5M norepinephrine, while the beta-agonist enhanced the contraction. The pretreatment with a beta-antagonist(ICI118551) reduced the tension of the strips developed by 10-4M isoproterenol, but the beta-(atenolol) and beta-(SR59230A) antagonists showed no changes in the response. CONCLUSIONS: beta- and beta-adrenoceptors seem to mediate the relaxation of the seminal vesicle, while the beta-adrenoceptor may have a supplementary role in contraction.

Effects of tumor necrosis factor alpha on beta-adrenoceptor and beta-adrenoceptor related GRKs in rat PMVEC / 第三军医大学学报

Objective To investigate the effects of tumor necrosis factor ? (TNF ?) on ? adrenoceptor (? AR) and ? AR related G protein coupled receptor kinases (GRKs) in rat pulmonary microvascular endothelial cells (PMVECs) as well as the interfering action of anisodamine. Methods Radio ligand binding assay was used to measure the maximal binding capacity (B max ) changes of ? AR in rat PMVECs after treatment with TNF ?. The effects of TNF ? and ? AR related GRKs expression at the protein level were observed by Western blotting. Results B max of ? AR in normal rat PMVECs was (5.58?0.31) fmol/10 5 cells. B max of ? AR in TNF ? group decreased significantly as compared with that in the normal control group, but no significant difference was found between the normal control group and TNF ?+anisodamine group. The expression of GRK2 in rat PMVECs was positive, but expression of GRK3, GRK5, and GRK6 were negative. The expression of GRK2 in TNF ? group and TNF ?+anisodamine group increased significantly as compared with that in the normal control group, but no significant difference was found between the TNF ? group and the TNF ?+anisodamine group. Conclusion GRK2 but not GRK3, GRK5, or GRK6 is expressed in rat PMVECs. The increased expression of GRK2 induced by TNF ? in rat PMVECs might promote the phosphorylation of ? AR, leading to ? AR internalization and decoupling with G protein, which might be the main mechanism of down regulation of ? AR induced by TNF ?. Anisodamine might inhibit the down regulation of ? AR through other mechanism instead of inhibiting the increase of GRK2 expression.

The Effects of beta-adrenocreptor Stimulation on the Maxi-K+ Channels in Human Corporal Smooth Muscle Cells / 대한비뇨기과학회지

PURPOSE: beta-adrenoceptors have been demonstrated in human corporal smooth muscles by the receptor binding assays, and have been known to elicit relaxation of the precontracted corporal tissues. Despite these findings, it is not clear whether the beta-adrenoceptors have any role in the control of penile erection. Potassium channels play an important role in the physiology of the corporal smooth muscle. The maxi-K+ channel subtypes are thought to be the most physiologically relevant K+ channels expressed in this tissue. The goal of this study was to clarify the contribution of the beta-adrenoceptors to the modulation of the corporal smooth muscle tone. MATERIALS AND METHODS: Patch-clamp technique was applied to the cultured human corporal smooth muscle cells. RESULTS: Maxi-K+ channel was activated by the application of the beta-adrenoceptor stimulator, isoproterenol (ISO). ISO increased the open probability (nP0) by 512+/-53% and the mean open time by 214+/-12% in the cell-attached patch recording. The whole cell patch recording indicated that the application of ISO in the bath solution increased the peak amplitude of the whole cell outward K+-current during the step depolarization (from -70 to + 130 mV). The presence of a specific protein kinase A inhibitor (PKI) in the pipette tip suppressed the ISO-induced increase of the whole cell outward K+-current. CONCLUSIONS: These studies showed that the beta-adrenoceptor activation contributed to the modulation of the corporal smooth muscle tone by activating the potassium channels, and moreover, that the activation of the potassium channels by the beta-adrenoceptors was related to the protein kinase A pathway.