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Talmir Augusto Faria Brizola Dos Santos - One of the best experts on this subject based on the ideXlab platform.
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Subfornical organ mediates pressor effect of Angiotensin: Influence of nitric oxide synthase inhibitors, AT1 and AT2 Angiotensin Antagonist's receptors
Journal of the American Society of Hypertension : JASH, 2008Co-Authors: Wilson Abrão Saad, Luiz Antonio De Arruda Camargo, Ismael Francisco Motta Siqueira Guarda, Talmir Augusto Faria Brizola Dos SantosAbstract:Abstract We investigated the influence of voltage-dependent calcium channels and nitric oxide (NO) on Angiotensin II (ANG II)-pressor effect injected into subfornical organ (SFO). The influence of NO on nifedipine antipressor action has also been studied by utilizing N W -nitro-L-arginine methyl ester (L-NAME) (20 μg × 0.2 μl −1 ) a nitric oxide synthase inhibitor (NOSI) and 7-nitroindazole (7-NIT) (20 μg × 0.2 μl −1 ), a specific neuronal nitric oxide synthase inhibitor (nNOSI). We have also investigated the role of losartan and PD123319, selective ANG II AT 1 and AT 2 receptor nonpeptide Antagonists, in the pressor effect of ANG II and in the effect of L-NAME and 7-NIT, injected into the SFO. Adult male Holtzman rats (220 to 280 g) were anesthetized with ketamine (80 mg/kg −1 of body weight) plus xylazine (7 mg/kg −1 of body weight), placed in a stereotaxic apparatus (David Kopf model for rats), and implanted with cannula into the SFO. Direct mean arterial blood pressure (MAP) was recorded in conscious rats in a test cage, without access to food or water. The previously implanted catheter into femoral artery was connected to a Statham (P23 Db) pressure transducer (Statham-Gould, Valley View, OH) coupled to a multichannel recorder (PowerLab Multirecord). MAP increased after ANG II injection. Pre-treatment with nifidipine (50 μg × 0.2 μl −1 or 100 μg × 0.2 μl −1 ) followed by 25 pmol × 0.2 μl −1 of ANG II, decreased ANG II-pressor effect. L-NAME and 7-NIT increased the elevation in MAP induced by ANG II, which was blocked by the prior injection of nifedipine. The AT 1 Angiotensin Antagonist losartan injected into the SFO blocked the effect of ANG II and the effects of L-NAME and 7-NIT while PD123319 did not. These results provide evidence that ANG II-pressor effect is influenced by nitrergic pathways that utilize L-type calcium channels in the SFO.
Wilson Abrão Saad - One of the best experts on this subject based on the ideXlab platform.
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Subfornical organ mediates pressor effect of Angiotensin: Influence of nitric oxide synthase inhibitors, AT1 and AT2 Angiotensin Antagonist's receptors
Journal of the American Society of Hypertension : JASH, 2008Co-Authors: Wilson Abrão Saad, Luiz Antonio De Arruda Camargo, Ismael Francisco Motta Siqueira Guarda, Talmir Augusto Faria Brizola Dos SantosAbstract:Abstract We investigated the influence of voltage-dependent calcium channels and nitric oxide (NO) on Angiotensin II (ANG II)-pressor effect injected into subfornical organ (SFO). The influence of NO on nifedipine antipressor action has also been studied by utilizing N W -nitro-L-arginine methyl ester (L-NAME) (20 μg × 0.2 μl −1 ) a nitric oxide synthase inhibitor (NOSI) and 7-nitroindazole (7-NIT) (20 μg × 0.2 μl −1 ), a specific neuronal nitric oxide synthase inhibitor (nNOSI). We have also investigated the role of losartan and PD123319, selective ANG II AT 1 and AT 2 receptor nonpeptide Antagonists, in the pressor effect of ANG II and in the effect of L-NAME and 7-NIT, injected into the SFO. Adult male Holtzman rats (220 to 280 g) were anesthetized with ketamine (80 mg/kg −1 of body weight) plus xylazine (7 mg/kg −1 of body weight), placed in a stereotaxic apparatus (David Kopf model for rats), and implanted with cannula into the SFO. Direct mean arterial blood pressure (MAP) was recorded in conscious rats in a test cage, without access to food or water. The previously implanted catheter into femoral artery was connected to a Statham (P23 Db) pressure transducer (Statham-Gould, Valley View, OH) coupled to a multichannel recorder (PowerLab Multirecord). MAP increased after ANG II injection. Pre-treatment with nifidipine (50 μg × 0.2 μl −1 or 100 μg × 0.2 μl −1 ) followed by 25 pmol × 0.2 μl −1 of ANG II, decreased ANG II-pressor effect. L-NAME and 7-NIT increased the elevation in MAP induced by ANG II, which was blocked by the prior injection of nifedipine. The AT 1 Angiotensin Antagonist losartan injected into the SFO blocked the effect of ANG II and the effects of L-NAME and 7-NIT while PD123319 did not. These results provide evidence that ANG II-pressor effect is influenced by nitrergic pathways that utilize L-type calcium channels in the SFO.
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Research Article Subfornical organ mediates pressor effect of Angiotensin: Influence of nitric oxide synthase inhibitors, AT 1 and AT 2 Angiotensin Antagonist's receptors
2008Co-Authors: Wilson Abrão Saad, Luiz Antonio De Arruda, Ismael Francisco, Motta Siqueira GuardaAbstract:We investigated the influence of voltage-dependent calcium channels and nitric oxide (NO) on Angiotensin II (ANG II)-pressor effect injected into subfornical organ (SFO). The influence of NO on nifedipine antipressor action has also been studied by utilizing N W -nitro-L-arginine methyl ester (L-NAME) (20 g 0.2 l 1 ) a nitric oxide synthase inhibitor (NOSI) and 7-nitroindazole (7-NIT) (20 g 0.2 l 1 ), a specific neuronal nitric oxide synthase inhibitor (nNOSI). We have also investigated the role of losartan and PD123319, selective ANG II AT1 and AT2 receptor nonpeptide Antagonists, in the pressor effect of ANG II and in the effect of L-NAME and 7-NIT, injected into the SFO. Adult male Holtzman rats (220 to 280 g) were anesthetized with ketamine (80 mg/kg 1 of body weight) plus xylazine (7 mg/kg 1 of body weight), placed in a stereotaxic apparatus (David Kopf model for rats), and implanted with cannula into the SFO. Direct mean arterial blood pressure (MAP) was recorded in conscious rats in a test cage, without access to food or water. The previously implanted catheter into femoral artery was connected to a Statham (P23 Db) pressure transducer (Statham-Gould, Valley View, OH) coupled to a multichannel recorder (PowerLab Multirecord). MAP increased after ANG II injection. Pre-treatment with nifidipine (50 g 0.2 l 1 or 100 g 0.2 l 1 ) followed by 25 pmol 0.2 l 1 of ANG II, decreased ANG II-pressor effect. L-NAME and 7-NIT increased the elevation in MAP induced by ANG II, which was blocked by the prior injection of nifedipine. The AT1 Angiotensin Antagonist losartan injected into the SFO blocked the effect of ANG II and the effects of L-NAME and 7-NIT while PD123319 did not. These results provide evidence that ANG II-pressor effect is influenced by nitrergic pathways that utilize L-type calcium channels in the SFO. J Am Soc Hypertens 2008;2(5): 326‐331. © 2008 American
Keith M Kendrick - One of the best experts on this subject based on the ideXlab platform.
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human extinction learning is accelerated by an Angiotensin Antagonist via ventromedial prefrontal cortex and its connections with basolateral amygdala
Biological Psychiatry, 2019Co-Authors: Feng Zhou, Yayuan Geng, Fei Xin, Pan Feng, Congcong Liu, Weihua Zhao, Tingyong Feng, Adam J Guastella, Richard P Ebstein, Keith M KendrickAbstract:Abstract Background Deficient extinction learning and threat adaptation in the ventromedial prefrontal cortex (vmPFC)-amygdala circuitry strongly impede the efficacy of exposure-based interventions in anxiety disorders. Recent animal models suggest a regulatory role of the renin-Angiotensin system in both these processes. Against this background, the present randomized placebo-controlled pharmacologic functional magnetic resonance imaging experiment aimed at determining the extinction enhancing potential of the Angiotensin II type 1 receptor Antagonist losartan (LT) in humans. Methods Seventy healthy male subjects underwent Pavlovian threat conditioning and received single-dose LT (50 mg) or placebo administration before extinction. Psychophysiological threat reactivity (skin conductance response) and neural activity during extinction served as primary outcomes. Psychophysiological interaction, voxelwise mediation, and novel multivariate pattern classification analyses were used to determine the underlying neural mechanisms. Results LT significantly accelerated the decline of the psychophysiological threat response during within-session extinction learning. On the neural level, the acceleration was accompanied and critically mediated by threat-specific enhancement of vmPFC activation. Furthermore, LT enhanced vmPFC-basolateral amygdala coupling and attenuated the neural threat expression, particularly in the vmPFC, during early extinction. Conclusions Overall the results indicate that LT facilitates within-session threat memory extinction by augmenting threat-specific encoding in the vmPFC and its regulatory control over the amygdala. The findings document a pivotal role of Angiotensin regulation of extinction learning in humans and suggest that adjunct LT administration has the potential to facilitate the efficacy of exposure-based interventions in anxiety disorders.
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human extinction learning is accelerated by an Angiotensin Antagonist via ventromedial prefrontal cortex and its connections with basolateral amygdala
bioRxiv, 2019Co-Authors: Feng Zhou, Yayuan Geng, Pan Feng, Congcong Liu, Weihua Zhao, Tingyong Feng, Adam J Guastella, Keith M Kendrick, Benjamin BeckerAbstract:Abstract Extinction is considered a core mechanism underlying exposure-based therapy in anxiety-related disorders. However, marked impairments in threat extinction learning coupled with impaired neuroplasticity in patients strongly impede the efficacy of exposure-based interventions. Recent translational research suggests a role of the renin-Angiotensin (RA) system in both these processes. However, the efficacy of pharmacological modulation of the RA system to enhance threat extinction in humans and the underlying neural mechanisms remain unclear. The present pre-registered, randomized placebo-controlled pharmacological neuroimaging trial demonstrates that pre-extinction administration of the Angiotensin II type 1 receptor Antagonist losartan accelerated attenuation of the psychophysiological threat response during extinction. On the neural level the acceleration of extinction was accompanied by threat-signal specific enhanced ventromedial prefrontal cortex (vmPFC) activation and its coupling with the basolateral amygdala. Multivoxel pattern analysis and voxel-wise mediation analysis further revealed that that losartan reduced the neural threat expression, particularly in the vmPFC, and confirmed that acceleration of extinction critically involved treatment-induced modulation of vmPFC activation. Overall the results provide the first evidence for a pivotal role of the RA system in extinction learning in humans and suggest that adjunct losartan administration can be leveraged to facilitate the efficacy of extinction-based therapies.
Sadaaki Iwanaga - One of the best experts on this subject based on the ideXlab platform.
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Substrate specificity of rabbit liver metalloendopeptidase and its new fluorogenic peptide substrates.
Journal of Biochemistry, 1995Co-Authors: Naoko Kojima, Norikazu Nishino, Shun-ichiro Kawabata, Yuichi Makinose, Sadaaki IwanagaAbstract:: A metalloendopeptidase (MEP) isolated from rabbit liver microsomes with substrate specificity for peptides containing Arg at the P1 and P4 positions has recently proved to be identical to soluble Angiotensin-binding protein present in the cytosol. Here we describe the peptide-degrading specificity of MEP, determined using various bioactive peptides and novel fluorogenic substrates for the enzyme. MEP degraded oligopeptides, including bradykinin, alpha-neoendorphin, bovine adrenal medulla dodecapeptide, substance P, bombesin, neurotensin, and alpha-endorphin, but not polypeptides such as reduced lysozyme and histone H4, hence, MEP probably belongs to the family of endo-oligopeptidases. It cleaved most preferentially at the -Phe-Ser- bond of bradykinin (kcat/Km = 2.8 x 10(4) M-1.S-1) but did not cleave high molecular weight and low molecular weight kininogens, the precursors of bradykinin. MEP did not cleave Angiotensin I, dynorphin A 1-13, somatostatin, and luteinizing hormone-releasing hormone, some of which are good substrates for metalloendopeptidase-24.15, metalloendopeptidase-24.16, N-arginine dibasic convertase, and yeast endopeptidase-24.15 related peptidase. An active site-directed inhibitor of metalloendopeptidase-24.15, N-[1-(R,S)-carboxyl-3-phenylpropyl]-Ala-Ala-Phe-p-aminobenzoate also had no effects on the amidolytic activity of MEP. Based on the cleavage sites of bioactive peptides and processing sites of vitamin K-dependent proproteins, intramolecularly quenched fluorogenic peptide substrates were newly synthesized. Among the thirteen substrates used, the most reactive was 2-aminobenzoyl-Ala-Arg-Val-Arg-Arg-Ala- Asn-Ser-2,4-dinitroanilinoethylamide (kcat/Km = 9.3 x 10(5) M-1.S-1). An Angiotensin Antagonist, [Sar1, Ala8]-Angiotensin II, inhibited hydrolysis of the substrate by MEP in a competitive manner (Kl = 7.6 microM). MEP cleaved oligopeptides even on the carboxyl side of proline residue and these peptides are resistant to hydrolysis by the cytosol-derived proteasome, therefore MEP may participate in the catabolism of oligopeptides in the cytosol, together with other endo-oligopeptidases.
M Iino - One of the best experts on this subject based on the ideXlab platform.
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Dynamic Ca2+ signalling in rat arterial smooth muscle cells under the control of local renin-Angiotensin system.
The Journal of physiology, 1999Co-Authors: Y Asada, T Yamazawa, K Hirose, T Takasaka, M IinoAbstract:1. We visualized the changes in intracellular Ca2+ concentration ([Ca2+]i), using fluo-3 as an indicator, in individual smooth muscle cells within intact rat tail artery preparations. 2. On average in about 45 % of the vascular smooth muscle cells we found spontaneous Ca2+ waves and oscillations ( approximately 0.13 Hz), which we refer to here as Ca2+ ripples because the peak amplitude of [Ca2+]i was about one-seventh of that of Ca2+ oscillations evoked by noradrenaline. 3. We also found another pattern of spontaneous Ca2+ transients often in groups of two to three cells. They were rarely observed and are referred to as Ca2+ flashes because their peak amplitude was nearly twice as large as that in noradrenaline-evoked responses. 4. Sympathetic nerve activity was not considered responsible for the Ca2+ ripples, and they were abolished by inhibitors of either the Ca2+ pump in the sarcoplasmic reticulum (cyclopiazonic acid) or phospholipase C (U-73122). 5. Both Angiotensin Antagonists ([Sar1,Ile8]-Angiotensin II and losartan) and an Angiotensin converting enzyme inhibitor (captopril) inhibited the Ca2+ ripples. 6. The extracellular Ca2+-dependent tension borne by unstimulated arterial rings was reduced by the Angiotensin Antagonist by approximately 50 %. 7. These results indicate that the Ca2+ ripples are generated via inositol 1,4, 5-trisphosphate-induced Ca2+ release from the intracellular Ca2+ stores in response to locally produced Angiotensin II, which contributes to the maintenance of vascular tone.
