Augmentation of moxonidine-induced increase in ANP release by atrial hypertrophy

2004 ◽  
Vol 287 (1) ◽  
pp. H150-H156 ◽  
Author(s):  
Chunhua Cao ◽  
Chang Won Kang ◽  
Sung Zoo Kim ◽  
Suhn Hee Kim
Keyword(s):  
Pulse Pressure ◽  
Antagonistic Effect ◽  
Imidazoline Receptors ◽  
Imidazoline Receptor ◽  
Adrenoceptor Antagonist ◽  
Adrenoceptor Agonist ◽  
Relative Change ◽  
Dose Dependent ◽  
Regulation Of Blood Pressure

Imidazoline receptors are divided into I1 and I2 subtypes. I1-imidazoline receptors are distributed in the heart and are upregulated during hypertension or heart failure. The aim of this study was to define the possible role of I1-imidazoline receptors in the regulation of atrial natriuretic peptide (ANP) release in hypertrophied atria. Experiments were performed on isolated, perfused, hypertrophied atria from remnant-kidney hypertensive rats. The relatively selective I1-imidazoline receptor agonist moxonidine caused a decrease in pulse pressure. Moxonidine (3, 10, and 30 μmol/l) also caused dose-dependent increases in ANP secretion, but clonidine (an α2-adrenoceptor agonist) did not. Pretreatment with efaroxan (a selective I1-imidazoline receptor antagonist) or rauwolscine (a selective α2-adrenoceptor antagonist) inhibited the moxonidine-induced increases in ANP secretion and interstitial ANP concentration and decrease in pulse pressure. However, the antagonistic effect of efaroxan on moxonidine-induced ANP secretion was greater than that of rauwolscine. Neither efaroxan nor rauwolscine alone has any significant effects on ANP secretion and pulse pressure. In hypertrophied atria, the moxonidine-induced increase in ANP secretion and decrease in pulse pressure were markedly augmented compared with nonhypertrophied atria, and the relative change in ANP secretion by moxonidine was positively correlated to atrial hypertrophy. The accentuation by moxonidine of ANP secretion was attenuated by efaroxan but not by rauwolscine. These results show that moxonidine increases ANP release through (preferentially) the activation of atrial I1-imidazoline receptors and also via different mechanisms from clonidine, and this effect is augmented in hypertrophied atria. Therefore, we suggest that cardiac I1-imidazoline receptors play an important role in the regulation of blood pressure.

Inhibition of α-adrenergic tone disturbs the distribution of blood flow in the exercising human limb

2013 ◽  
Vol 305 (2) ◽  
pp. H163-H172 ◽  
Author(s):  
Ilkka Heinonen ◽  
Maria Wendelin-Saarenhovi ◽  
Kimmo Kaskinoro ◽  
Juhani Knuuti ◽  
Mika Scheinin ◽  
...  
Keyword(s):  
Blood Flow ◽  
Oxygen Extraction ◽  
Adrenoceptor Antagonist ◽  
Leg Muscles ◽  
Exercise Condition ◽  
Positron Emission ◽  
Adrenoceptor Agonist ◽  
Neuronal Regulation ◽  
Human Limb

The role of neuronal regulation of human cardiovascular function remains incompletely elucidated, especially during exercise. Here we, by positron emission tomography, monitored tissue-specific blood flow (BF) changes in nine healthy young men during femoral arterial infusions of norepinephrine (NE) and phentolamine. At rest, the α-adrenoceptor agonist NE reduced BF by ∼40%, similarly in muscles (from 3.2 ± 1.9 to 1.4 ± 0.3 ml·min−1·100 g−1 in quadriceps femoris muscle), bone (from 1.1 ± 0.4 to 0.5 ± 0.2 ml·min−1·100 g−1) and adipose tissue (AT) (from 1.2 ± 0.7 to 0.7 ± 0.3 ml·min−1·100 g−1). During exercise, NE reduced exercising muscle BF by ∼16%. BF in AT was reduced similarly as rest. The α-adrenoceptor antagonist phentolamine increased BF similarly in the different muscles and other tissues of the limb at rest. During exercise, BF in inactive muscle was increased 3.4-fold by phentolamine compared with exercise without drug, but BF in exercising muscles was not influenced. Bone and AT ( P = 0.055) BF were also increased by phentolamine in the exercise condition. NE increased and phentolamine decreased oxygen extraction in the limb during exercise. We conclude that inhibition of α-adrenergic tone markedly disturbs the distribution of BF and oxygen extraction in the exercising human limb by increasing BF especially around inactive muscle fibers. Moreover, although marked functional sympatholysis also occurs during exercise, the arterial NE infusion that mimics the exaggerated sympathetic nerve activity commonly seen in patients with cardiovascular disease was still capable of directly limiting BF in the exercising leg muscles.

The Effect of Imidazoline Receptors and α2-adrenoceptors on the Anesthetic Requirement (MAC) for Halothane in Rats 

1997 ◽  
Vol 87 (4) ◽  
pp. 963-967 ◽  
Author(s):  
Kiyokazu Kagawa ◽  
Tadanori Mammoto ◽  
Yukio Hayashi ◽  
Takahiko Kamibayashi ◽  
Takashi Mashimo ◽  
...  
Keyword(s):  
Minimum Alveolar Concentration ◽  
Inhibitory Effect ◽  
Imidazoline Receptors ◽  
Adrenoceptor Antagonist ◽  
Adrenoceptor Agonist ◽  
Adrenoceptor Agonists ◽  
The Central Nervous System ◽  
Anesthetic Requirement ◽  
Alpha2 Adrenoceptor ◽  
Pharmacologic Actions

Background Recent evidences have documented that several pharmacologic actions of alpha2-adrenoceptor agonists are mediated via activation of not only alpha2-adrenoceptors, but also by imidazoline receptors, which are nonadrenergic receptors in the central nervous system. However, the effect of imidazoline receptors on the anesthesia is not well known, and it is important to clarify the effects of both receptors on anesthesia. Methods Seventy-two rats were anesthetized with halothane, and the anesthetic requirement for halothane was evaluated as minimum alveolar concentration (MAC). The MAC for halothane was determined in the presence of dexmedetomidine (0, 10, 20, and 30 microg/kg, intraperitoneally [IP]), a selective alpha2-adrenoceptor agonist with weak affinity for imidazoline receptors. Then, the authors evaluated the inhibitory effect of rauwolscine (20 mg/kg, IP), an alpha2-adrenoceptor antagonist with little affinity for imidazoline receptors, on the MAC-reducing action of dexmedetomidine (30 microg/kg). Further, the effect of rilmenidine (20, 50, 100, 1000 microg/kg, IP), a selective imidazoline receptor agonist, on the MAC for halothane was also investigated. Results Dexmedetomidine decreased the MAC for halothane dose-dependently, and this MAC-reducing action of dexmedetomidine was completely blocked by rauwolscine. Rilmenidine alone did not change the MAC for halothane. Conclusions The present data indicate that the anesthetic sparing action of dexmedetomidine is most likely mediated through alpha2- adrenoceptors, and the stimulation of imidazoline receptors exerts little effect on the anesthetic requirement for halothane.

Role of AT2 receptor in the brain in regulation of blood pressure and water intake

2003 ◽  
Vol 284 (1) ◽  
pp. H116-H121 ◽  
Author(s):  
Zhen Li ◽  
Masaru Iwai ◽  
Lan Wu ◽  
Tetsuya Shiuchi ◽  
Toyohisa Jinno ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Water Intake ◽  
Pressor Response ◽  
Receptor Blocker ◽  
Dependent Manner ◽  
Ang Ii ◽  
Dose Dependent ◽  
Regulation Of Blood Pressure

The effects of intracerebroventricular (ICV) injection of angiotensin II (ANG II) on blood pressure and water intake were examined with the use of ANG II receptor-deficient mice. ICV injection of ANG II increased systolic blood pressure in a dose-dependent manner in wild-type (WT) mice and ANG type 2 AT2 receptor null (knockout) (AT2KO) mice; however, this increase was significantly greater in AT2KO mice than in WT mice. The pressor response to a central injection of ANG II in WT mice was inhibited by ICV preinjection of the selective AT1 receptor blocker valsartan but exaggerated by the AT2 receptor blocker PD-123319. ICV injection of ANG II also increased water intake. It was partly but significantly suppressed both in AT2KO and AT1aKO mice. Water intake in AT2/AT1aKO mice did not respond to ICV injection of ANG II. Both valsartan and PD-123319 partly inhibited water intake in WT mice. These results indicate an antagonistic action between central AT1a and AT2 receptors in the regulation of blood pressure, but they act synergistically in the regulation of water intake induced by ANG II.

Endothelin-1 enhances cross-bridge function of ferret myocardium: role of second messengers

1993 ◽  
Vol 265 (6) ◽  
pp. H2168-H2174
Author(s):  
J. Wang ◽  
K. Flemal ◽  
J. P. Morgan
Keyword(s):  
Myocardial Contractility ◽  
Second Messengers ◽  
Tension Development ◽  
Endothelin 1 ◽  
Adrenoceptor Agonist ◽  
Similar Dose ◽  
Butanedione Monoxime ◽  
The Right ◽  
Dose Dependent

To investigate postreceptor pathways of endothelin and the site of action responsible for enhancing myocardial contractility, studies were performed on ferret papillary muscles loaded with the Ca2+ indicator aequorin. Endothelin-1 (ET) and the alpha 1-adrenoceptor agonist, phenylephrine (PE) produced similar dose-dependent increases in tension development and peak intracellular Ca2+ concentration ([Ca2+]i); moreover, pretreatment with PE eliminated effects of ET, suggesting similar postreceptor pathways. Because alpha 1-adrenoceptor activation is thought to cause the hydrolysis of phosphatidylinositol and generate D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] and 1,2-diacylglycerol (DAG), the protein kinase C (PKC) activator 4 beta-phorbol 12-myristate 13-acetate (PMA) was used to determine whether activation of PKC was responsible for the myocardial actions of ET. In contrast to ET, PMA decreased tension development and peak [Ca2+]i, and pretreatment with PMA attenuated the myocardial action of ET; however, intracellular Ins(1,4,5)P3 levels were greatly increased by ET stimulation, suggesting that rather than DAG, Ins(1,4,5)P3 might be the second messenger for the actions of ET. To determine whether ET produced actions on the contractile elements, thereby enhancing myocardial contractility, 2,3-butanedione monoxime (BDM) was used to interfere with the interaction of myosin and actin. Pretreatment with 6 mM BDM did not alter the half-maximum effective concentration (EC50) of the [Ca2+]o-tension relation, but, in contrast, shifted the ET dose-response curve to the right, and increased the EC50 by approximately 1.0 log unit. In addition, ET partially reversed the downward shift of the peak [Ca2+]i-peak tension curve induced by BDM.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of endothelin in α-adrenoceptor coronary vasoconstriction

2005 ◽  
Vol 288 (4) ◽  
pp. H1937-H1942 ◽  
Author(s):  
Mark W. Gorman ◽  
Martin Farias ◽  
Keith N. Richmond ◽  
Johnathan D. Tune ◽  
Eric O. Feigl
Keyword(s):  
Oxygen Tension ◽  
Endothelin Receptor ◽  
Coronary Smooth Muscle ◽  
Coronary Vasoconstriction ◽  
Adrenoceptor Antagonist ◽  
Adrenoceptor Agonist ◽  
Resistance Vessels ◽  
Anesthetized Dogs ◽  
The Difference

It has been proposed that α-adrenoceptor vasoconstriction in coronary resistance vessels results not from α-adrenoceptors on coronary smooth muscle but from α-adrenoceptors on cardiac myocytes that stimulate endothelin (ET) release. The present experiments tested the hypothesis that the α-adrenoceptor-mediated coronary vasoconstriction that normally occurs during exercise is due to endothelin. In conscious dogs ( n = 10), the endothelin ETA/ETB receptor antagonist tezosentan (1 mg/kg iv) increased coronary venous oxygen tension at rest but not during treadmill exercise. This result indicates that basal endothelin levels produce a coronary vasoconstriction at rest that is not observed during the coronary vasodilation during exercise. In contrast, the α-adrenoceptor antagonist phentolamine increased coronary venous oxygen tension during exercise but not at rest. The difference between the endothelin blockade and α-adrenoceptor blockade results indicates that α-adrenoceptor coronary vasoconstriction during exercise is not due to endothelin. However, in anesthetized dogs, bolus intracoronary injections of the α-adrenoceptor agonist phenylephrine produced reductions in coronary blood flow that were partially antagonized by endothelin receptor blockade with tezosentan. These results are best explained if α-adrenoceptor-induced endothelin release requires high pharmacological concentrations of catecholamines that are not reached during exercise.

Central catecholaminergic neurons are involved in expression of the 10-Hz rhythm in SND

1996 ◽  
Vol 270 (2) ◽  
pp. R333-R341 ◽  
Author(s):  
H. S. Orer ◽  
S. Zhong ◽  
S. M. Barman ◽  
G. L. Gebber
Keyword(s):  
Intravenous Administration ◽  
Sympathetic Nerve ◽  
Ventrolateral Medulla ◽  
Imidazoline Receptors ◽  
Catecholaminergic Neurons ◽  
Adrenoceptor Antagonist ◽  
Adrenoceptor Agonist ◽  
Adrenoceptor Agonists ◽  
Nerve Discharge ◽  
Lower Frequencies

We studied the effects of adrenoceptor agonists and antagonists on sympathetic nerve discharge (SND) of urethan-anesthetized, baroreceptor-denervated cats. In cats in which a 10-Hz rhythm coexisted with irregular 2- to 6-Hz oscillations in SND, intravenous clonidine, an alpha 2-adrenoceptor agonist, blocked the 10-Hz rhythm without affecting power at lower frequencies. In contrast, power at frequencies < or = 6 Hz was depressed by clonidine in cats in which the 10-Hz rhythm was absent. These effects were reversed by intravenous administration of alpha 2-adrenoceptor antagonists, idazoxan and rauwolscine. Rauwolscine is devoid of affinity for imidazoline receptors. Furthermore, in cats untreated with clonidine, idazoxan and rauwolscine enhanced or induced the 10-Hz rhythm without affecting power at lower frequencies. Prazosin, an alpha 1-adrenoceptor antagonist, selectively blocked the 10-Hz rhythm in SND. Finally, the 10-Hz rhythm in SND was blocked by microinjection of clonidine into the rostral or caudal ventrolateral medulla. The results support the view that central catecholaminergic neurons play a role in expression of the 10-Hz rhythm in SND.

Amelioration of Carbon Tetrachloride-Induced Liver Injury by Citrus Leaf Extract

2019 ◽  
Vol 17 (4) ◽  
pp. 426-431
Author(s):  
Jin Xuezhu ◽  
Li Jitong ◽  
Nie Leigang ◽  
Xue Junlai
Keyword(s):  
Carbon Tetrachloride ◽  
Leaf Extract ◽  
Hepatic Injury ◽  
The Body ◽  
Dependent Manner ◽  
Weight Changes ◽  
Citrus Leaf ◽  
Dose Dependent ◽  
And Oxidative Stress

The main purpose of this study is to investigate the role of citrus leaf extract in carbon tetrachloride-induced hepatic injury and its potential molecular mechanism. Carbon tetrachloride was used to construct hepatic injury animal model. To this end, rats were randomly divided into 4 groups: control, carbon tetrachloride-treated, and two carbon tetrachloride + citrus leaf extract-treated groups. The results show that citrus leaf extract treatment significantly reversed the effects of carbon tetrachloride on the body weight changes and liver index. Besides, treatment with citrus leaf extract also reduced the levels of serum liver enzymes and oxidative stress in a dose-dependent manner. H&E staining and western blotting suggested that citrus leaf extract could repair liver histological damage by regulating AMPK and Nrf-2.

Investigation on the antibacterial activity of electronic cigarette liquids (ECLs): a proof of concept study

2020 ◽  
Vol 21 ◽  
Author(s):  
Virginia Fuochi ◽  
Massimo Caruso ◽  
Rosalia Emma ◽  
Aldo Stivala ◽  
Riccardo Polosa ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Bacterial Species ◽  
A549 Cells ◽  
Bactericidal Effect ◽  
Minimal Bactericidal Concentration ◽  
Viability Assay ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Dose Dependent

Background: The key ingredients of e-cigarettes liquid are commonly propane-1,2-diol (also called propylene glycol) and propane-1,2,3-triol (vegetal glycerol) and their antimicrobial effects are already established. The nicotine and flavors which are often present in e-liquids can interfere with the growth of some microorganisms. Objective: The effect of the combining these elements in e-liquids is unknown. The aim of the study was to investigate the possible effects of these liquids on bacterial growth in the presence or absence of nicotine and flavors. Methods: Susceptibilities of pathogenic strains (Klebsiella pneumoniae, Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, Escherichia coli, Enterococcus faecalis and Sarcina lutea) were studied by means of a multidisciplinary approach. Cell viability and antioxidant assays were also evaluated. Results: All e-liquids investigated showed antibacterial activity against at least one pathogenic strain. A higher activity was correlated to the presence of flavors and nicotine. Discussion: In most cases the value of minimal bactericidal concentration is equal to the value of minimal inhibitory concentration showing that these substances have a bactericidal effect. This effect was observed in concentrations up to 6.25% v/v. Antioxidant activity was also correlated to presence of flavors. Over time, the viability assay in human epithelial lung A549 cells showed a dose-dependent inhibition of cell growth. Conclusion: Our results have shown that flavors considerably enhance the antibacterial activity of propane-1,2-diol and propane-1,2,3-triol. This study provides important evidence that should be taken into consideration in further investigative approaches, to clarify the different sensitivity of the various bacterial species to e-liquids, including the respiratory microbiota, to highlight the possible role of flavors and nicotine.

Changes in growth rate and thyroid- and sex-hormones blood levels in rats under sub-chronic lithium treatment

2006 ◽  
Vol 25 (5) ◽  
pp. 243-250 ◽  
Author(s):  
M S Allagui ◽  
N Hfaiedh ◽  
C Vincent ◽  
F Guermazi ◽  
J-C Murat ◽  
...  
Keyword(s):  
Growth Rate ◽  
Lithium Treatment ◽  
Lithium Carbonate ◽  
Serum Levels ◽  
Antagonistic Effect ◽  
Blood Levels ◽  
Vaginal Mucosa ◽  
Dependent Manner ◽  
Serum Concentrations ◽  
Dose Dependent

Lithium therapy, mainly used in curing some psychiatric diseases, is responsible for numerous undesirable side effects. The present study is a contribution to the understanding of the pathophysiological mechanisms underlying lithium toxicity. Male and female mature rats were divided into three batches and fed commercial pellets: one batch was the control and the second and third batches were given 2 g (Li1) and 4 g (Li2) of lithium carbonate/kg of food/day, respectively. After 7, 14, 21 and 28 days, serum levels of free tri-iodothyronine (FT3), thyroxine (FT4), testosterone and estradiol were measured. Attention was also paid to growth rate and a histological examination of testes or vaginal mucosa was carried out. In treated rats, a dose-dependent loss of appetite and a decrease in growth rate were observed, together with symptoms of polydypsia, polyuria and diarrhea. Lithium serum concentrations increased from 0.44 mM (day 7) to 1.34 mM (day 28) in Li1 rats and from 0.66 to 1.45 mM (day 14) in Li2 rats. Li2 treatment induced a high mortality after 14 days, reaching 50-60% in female and male animals. From these data, the LD50 (14 days Li2 chronic treatment) was calculated to be about 0.3 g/day per kilogram of animal, leading to Li serum concentrations of about 1.4 mM. A significant decrease of FT3 and FT4 was observed in treated rats. This effect appeared immediately for the highest dose and was more pronounced for FT3, resulting in an increase of the FT4/FT3 ratio. In males, testosterone decreased and spermatogenesis was stopped. Conversely, in females, estradiol increased in a dose-dependent manner as the animals were blocked in the diestrus phase at day 28. This finding supports a possible antagonistic effect of lithium on the estradiol receptors.

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