Magnesium acetyltaurate protects against endothelin-1 induced RGC loss by reducing neuroinflammation in Sprague dawley rats

2020 ◽  
Vol 194 ◽  
pp. 107996 ◽  
Author(s):  
Natasha Najwa Nor Arfuzir ◽  
Renu Agarwal ◽  
Igor Iezhitsa ◽  
Puneet Agarwal ◽  
Nafeeza Mohd Ismail
2007 ◽  
Vol 292 (1) ◽  
pp. H245-H250 ◽  
Author(s):  
Zheng F. Ba ◽  
Ailing Lu ◽  
Tomoharu Shimizu ◽  
László Szalay ◽  
Martin G. Schwacha ◽  
...  

Although endothelin-1 (ET-1) induces vasoconstriction, it remains unknown whether 17β-estradiol (E2) treatment following trauma-hemorrhage alters these ET-1-induced vasoconstrictive effects. In addition, the role of the specific estrogen receptor (ER) subtypes (ER-α and ER-β) and the endothelium-localized downstream mechanisms of actions of E2 remain unclear. We hypothesized that E2 attenuates increased ET-1-induced vasoconstriction following trauma-hemorrhage via an ER-β-mediated pathway. To study this, aortic rings were isolated from male Sprague-Dawley rats following trauma-hemorrhage with or without E2 treatment, and alterations in tension were determined in vitro. Dose-response curves to ET-1 were determined, and the vasoactive properties of E2, propylpyrazole triol (PPT, ER-α agonist), and diarylpropionitrile (DPN, ER-β agonist) were determined. The results showed that trauma-hemorrhage significantly increased ET-1-induced vasoconstriction; however, administration of E2 normalized ET-1-induced vasoconstriction in trauma-hemorrhage vessels to the sham-operated control level. The ER-β agonist DPN counteracted ET-1-induced vasoconstriction, whereas the ER-α agonist PPT was ineffective. Moreover, the vasorelaxing effects of E2 were not observed in endothelium-denuded aortic rings or by pretreatment of the rings with a nitric oxide (NO) synthase inhibitor. Cyclooxygenase inhibition with indomethacin had no effect on the action of E2. Thus, E2 administration attenuates ET-1-induced vasoconstriction following trauma-hemorrhage via an ER-β-mediated pathway that is dependent on endothelium-derived NO synthesis.


1992 ◽  
Vol 83 (2) ◽  
pp. 165-170 ◽  
Author(s):  
Pi-Chin Yu ◽  
Jon-Son Kuo ◽  
Han-Chieh Lin ◽  
May C. M. Yang

1. Effects of endothelin-1 on systemic arterial blood pressure, heart rate and portal venous pressure were compared in normal Sprague-Dawley rats and rats with portal hypertension induced by CCl4 and partial portal vein ligation. 2. Endothelin-1 produced biphasic effects on systemic blood pressure and portal venous pressure in all three groups of rats. However, the magnitude of the changes in blood pressure was less in portal hypertensive rats. 3. The ability of endothelin-1 to increase the portal venous pressure was also significantly diminished in portal hypertensive rats. On the other hand, the initial decrease in portal pressure was augmented in rats with partial portal vein ligation, and disappeared at higher dosage in CCl4-treated rats. 4. In accordance with the pressure recording in vivo, the dose-response vasoconstrictive activity of endothelin-1 was significantly attenuated in the intrahepatic vasculature. 5. The plasma immunoreactive endothelin concentration was significantly higher (5.55 ± 0.81 fmol/ml) in Sprague-Dawley rats than in CCl4-treated rats (2.83 ± 0.56 fmol/ml) and rats with partial portal vein ligation (2.68 ± 0.53 fmol/ml). 6. It was concluded that a lower plasma level of endothelin and a reduced vascular responsiveness may contribute, at least in part, to the hyperdynamics of portal hypertension.


2019 ◽  
Vol 13 (1) ◽  
pp. 73-80 ◽  
Author(s):  
Natasha Najwa Nor Arfuzir ◽  
Renu Agarwal ◽  
Igor Iezhitsa ◽  
Puneet Agarwal ◽  
Nafeeza Mohd Ismail

2003 ◽  
Vol 284 (6) ◽  
pp. H1899-H1903 ◽  
Author(s):  
Ahmed A. Elmarakby ◽  
Peter Morsing ◽  
David M. Pollock

Recent studies have shown that angiotensin-converting enzyme (ACE) inhibitors attenuate endothelin-1 (ET-1)-induced hypertension, but the mechanisms for this effect have not been clarified. Initial experiments were conducted to contrast the effect of the ACE inhibitor enalapril, the combined ACE-neutral endopeptidase inhibitor omapatrilat, and the angiotensin II receptor antagonist candesartan on the hypertensive and renal response to ET-1 in anesthetized Sprague-Dawley rats. Acute intravenous infusion of ET-1 (10 pmol · kg−1 · min−1) for 60 min significantly increased mean arterial pressure (MAP) from 125 ± 8 to 145 ± 8 mmHg ( P < 0.05) and significantly decreased glomerular filtration rate (GFR) from 0.31 ± 0.09 to 0.13 ± 0.05 ml · min−1 · 100 g kidney wt−1. Pretreatment with enalapril (10 mg/kg iv) before ET-1 infusion inhibited the increase in MAP (121 ± 4 vs. 126 ± 4 mmHg) before and during ET-1 infusion, respectively ( P < 0.05) without blocking the effect of ET-1 on GFR. In contrast, neither omapatrilat (30 mg/kg) nor candesartan (10 mg/kg) had any effect on ET-1-induced increases in MAP or decreases in GFR. To determine whether the effect of enalapril was due to the decrease in angiotensin II or increase in kinin formation, rats were given REF-000359 (1 mg/kg iv), a selective B2 receptor antagonist, with or without enalapril before ET-1 infusion. REF-000359 completely blocked the effect of enalapril on ET-1 infusion (MAP was 117 ± 5 vs. 135 ± 5 mmHg before and during ET-1 infusion, respectively, P < 0.05). REF-000359 alone had no effect on the response to ET-1 infusion (MAP was 117 ± 4 vs. 144 ± 4 mmHg before and during ET-1 infusion, respectively, P < 0.05). REF-000359 with or without enalapril had no significant effect on the ability of ET-1 infusion to decrease GFR. These findings support the hypothesis that decreased catabolism of bradykinin and its subsequent vasodilator activity oppose the actions of ET-1 to increase MAP.


Hypertension ◽  
2019 ◽  
Vol 74 (Suppl_1) ◽  
Author(s):  
Reham H Soliman ◽  
Chunhua Jin ◽  
Crystal M Taylor ◽  
David M Pollock

1993 ◽  
Vol 85 (5) ◽  
pp. 593-597 ◽  
Author(s):  
Harald Michel ◽  
Angela Bäcker ◽  
Harald Meyer-Lehnert ◽  
Iris Migas ◽  
Herbert J. Kramer

1. In the present study we investigated, first, the effects of high Na+ intake and, second, the effects of water deprivation on plasma endothelin-1 concentration and urinary endothelin-1 excretion and on endothelin receptors in membranes of renal glomeruli and papillae and of aortic smooth muscle and lung tissue from 32 female Sprague-Dawley rats. 2. After 5 weeks of high Na+ intake (n = 8) urinary Na+ excretion was 10.5 + 1.3 compared with 1.6 + 0.2 mmol/24h in controls. Body weight, plasma osmolality, plasma endothelin-1 concentration (23 + 6 versus 28 + 3 fmol/ml) and urinary endothelin-1 excretion (6.1 + 13 versus 4.7 + 0.3 pmol/24 h) remained unchanged. 3. The characteristics of endothelin-1 receptors in glomeruli, papillae, aortic smooth muscle and lung tissue from salt-loaded rats were not different from those of controls. 4. After 48 h water deprivation (n = 8) body weight had decreased, whereas packed cell volume and plasma and urine osmolalities had increased compared with controls (n = 8) (P <0.05). Plasma endothelin-1 concentration (40 + 6 versus 21 + 2 fmol/ml) was higher (P <0.01) and urinary endothelin-1 excretion (1.0 + 0.2 versus 2.8 + 03 pmol/24 h) was lower than in controls (P <0.01). 5. Water deprivation was accompanied by increases in endothelin-1 binding sites in glomeruli (Bmax. 4.8 + 0.4 versus 3.6 + 0.2 pmol/mg of protein; P <0.05) with unchanged receptor affinity (Kd 56 + 9 versus 57 + 8 pmol/l), in papillae (Bmax. 8.0 + 0.7 versus 6.2 + 0.5 pmol/mg of protein; P <0.05) with unchanged Kd (78 + 6 versus 63 + 4 pmol/l) and in aortic smooth muscle cells (Bmax. 3.5 + 0.2 versus 2.8 + 0.2 pmol/mg of protein; P <0.05) in which Kd rose to 307 + 27 versus 180 + 22 pmol/l (P <0.05). Endothelin-1 receptors in lung tissue were unaltered (Bmax. 10.0 + 03 versus 103 + 0.8 pmol/mg of protein; Kd 152 + 12 versus 137 + 14 pmol/l). 6. Our results suggest that the peripheral endothelin-1 system may play a role in the adaptation to changes in body water content rather than in Na+ balance.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Li-mei Liao ◽  
Li Zhou ◽  
Chen-ran Wang ◽  
Jian-ying Hu ◽  
Yao-jun Lu ◽  
...  

Abstract Background Different from current cognition, our study demonstrated that adrenergic receptors agonist phenylephrine significantly relaxed isolated pulmonary artery but constricted pulmonary veins. Through comparing differences in the effects of commonly used vasoactive drugs on pulmonary artery and veins, the study aimed to improve efficiency and accuracy of isolated pulmonary vascular experiments, and to provide experimental basis for clinical drug use. Methods The contractile responses of pulmonary arteries and veins from twelve-week-old Male Sprague-Dawley rats to phenylephrine, arginine vasopressin (AVP), U46619, endothelin-1, and potassium chloride (KCl) were recorded, as well as the relaxation in response to phenylephrine, AVP, acetylcholine. To further explore the mechanism, some vessels was also pre-incubated with adrenergic receptors antagonists propranolol, prazosin and nitric oxide synthesis inhibitor N[gamma]-nitro-L-arginine methyl ester (L-NAME) before addition of the experimental drugs. Results Phenylephrine constricted pulmonary veins directly, but constricted pulmonary artery only after incubation with propranolol or/and L-NAME. The pulmonary artery exhibited significant relaxation to AVP with or without L-NAME incubation. AVP more clearly constricted the veins after incubation with L-NAME. Changes in vascular tension also varied from pulmonary artery to veins for KCl stimulation. Different from phenomena presented in veins, acetylcholine did not relax pulmonary artery preconstricted by KCl, U46619, and endothelin-1. Conclusions According to the results, phenylephrine, KCl, AVP, and acetylcholine could be used to distinguish pulmonary arteries and pulmonary veins in vitro. This also suggested that the pulmonary arteries and pulmonary veins have great differences in physiology and drug reactivity.


Author(s):  
D. J. McComb ◽  
J. Beri ◽  
F. Zak ◽  
K. Kovacs

Investigation of the spontaneous pituitary adenomas in rat have been limited mainly to light microscopic study. Furth et al. (1973) described them as chromophobic, secreting prolactin. Kovacs et al. (1977) in an ul trastructural investigation of adenomas of old female Long-Evans rats, found that they were composed of prolactin cells. Berkvens et al. (1980) using immunocytochemistry at the light microscopic level, demonstrated that some spontaneous tumors of old Wistar rats could contain GH, TSH or ACTH as well as PRL.


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