scholarly journals Progesterone Induced Blocking Factor Reduces Hypertension and Placental Mitochondrial Dysfunction with in Response to sFlt-1 during Pregnancy

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2817
Author(s):  
Evangeline Deer ◽  
Jalisa Jones ◽  
Denise Cornelius ◽  
Kyleigh Comley ◽  
Owen Herrock ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Arterial Blood Pressure ◽  
Mean Arterial Blood Pressure ◽  
Sprague Dawley ◽  
Arterial Blood ◽  
Blocking Factor ◽  
Sprague Dawley Rats ◽  
Inflammatory Processes ◽  
Placental Ischemia ◽  
And Oxidative Stress

Preeclampsia (PE) is characterized by new onset hypertension in association with placental ischemia, reduced fetal weight, elevated soluble fms-like tyrosine kinase-1 (sFlt-1), and placental mitochondrial (mt) dysfunction and oxidative stress (ROS). Progesterone induced blocking factor (PIBF) is a product of progesterone signaling that blocks inflammatory processes and we have previously shown PIBF to lower mean arterial blood pressure (MAP) and sFlt-1 in a rat model of PE. Infusion of sFlt-1 causes hypertension and many characteristics of PE in pregnant rodents, however, its role in causing mt dysfunction is unknown. Therefore, we hypothesize that PIBF will improve mt function and MAP in response to elevated sFlt-1 during pregnancy. We tested our hypothesis by infusing sFlt-1 via miniosmotic pumps in normal pregnant (NP) Sprague-Dawley rats (3.7 μg·kg−1·day−1) on gestation days (GD) 13–19 in the presence or absence of PIBF (2.0 µg/mL) injected intraperitoneally on GD 15 and examined mean arterial blood pressure (MAP) and placental mt ROS on GD 19. sFlt-1 increased MAP to 112 + 2 (n = 11) compared to NP rats (98 + 2 mmHg, n = 15, p < 0.05), which was lowered in the presence of sFlt-1 (100 + 1 mmHg, n = 5, p < 0.05). Placental mtATP was reduced in sFlt-1 infused rats versus NP controls, but was improved with PIBF. Placental mtROS was elevated with sFlt-1 compared to NP controls, but was reduced with PIBF. Sera from NP + sFlt-1 increased endothelial cell mtROS, which was attenuated with PIBF. These data demonstrate sFlt-1 induced HTN during pregnancy reduces placental mt function. Importantly, PIBF improved placental mt function and HTN, indicating the efficacy of improved progesterone signaling as potential therapeutics for PE.

Physiological Amounts of Angiotensinogen Increase Blood Pressure in Sprague Dawley Rats After I.V. Administration.

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 694-694
Author(s):  
Christoph P R Klett ◽  
Joey P Granger
Keyword(s):  
Blood Pressure ◽  
Arterial Blood Pressure ◽  
Transit Time ◽  
Mean Arterial Blood Pressure ◽  
Time Lag ◽  
Plasma Concentrations ◽  
Sprague Dawley ◽  
Angiotensin I ◽  
Arterial Blood ◽  
Sprague Dawley Rats

P9 The synthesis and secretion of hepatic angiotensinogen is controlled by a complex pattern of physiologic and pathophysiologic mediators including glucocorticoids, estrogens, thyroid hormones, cytokines, glucagon,insulin, and prostaglandins. Since plasma concentrations of angiotensinogen are close to the Michaelis Menten constant, it was hypothesized that changes in angiotensinogen plasma concentrations have an influence on the formation rate of angiotensin I and angiotensin II and, therefore, on blood pressure. To further test this hypothesis we injected purified rat angiotensinogen i.v. in Sprague Dawley rats via the femoral vein. Mean arterial blood pressure was measured after arterial cathederization. Control animals had a mean arterial pressure of 131 ± 2 mm Hg before and after the injection of vehicle (saline). The injection of 0.8, 1,2, and 2.9 mg/kg angiotensinogen caused a dose dependend increase in mean arterial blood pressure of 8 ± 0.4, 19.3 ± 2.1, and 32 ± 2.4 mm Hg, respectively. In contrast, the injection of a purified rabbit anti-rat-angiotensinogen antibody 1.4 mg/kg resulted in a significant decrease in blood pressure (-52 ± 3.2 mmHg). In an attempt to analyze how fast and efficient angiotensinogen production can sense regulatory input and convert into adaptation of secretion rate we determined the transit time (time needed for translation and post-translational modifications) for angiotensinogen in a pulse chase experiment employing 35 [S]-methionine as label in freshly isolated hepatocytes. During the chase periode, after quantitative immunoprecipitation, we determined the transit time for angiotensinogen with 2.5 h which is consistent with the constitutive type of angiotensinogen secretion and the time lag found for plasma concentrations to respond to regulatory mediators. In summary we conclude that variations in angiotensinogen plasma concentrations can result in changes in blood pressure. In contrast to renin known as a tonic regulator for the generation of angiotensin I, angiotensinogen seems to be a factor rather important for long-term control of the basal activity of the renin angiotensin system.

Orchidectomy attenuates impaired endothelial effects of a high-salt diet in Sprague–Dawley rats

2011 ◽  
Vol 89 (4) ◽  
pp. 295-304 ◽  
Author(s):  
A.K. Oloyo ◽  
O.A. Sofola ◽  
C.N. Anigbogu
Keyword(s):  
Blood Pressure ◽  
Arterial Blood Pressure ◽  
Mean Arterial Blood Pressure ◽  
High Salt ◽  
Sprague Dawley ◽  
High Salt Diet ◽  
Salt Diet ◽  
Arterial Blood ◽  
Sprague Dawley Rats ◽  
Induced Hypertension

The effect of sex hormones on vascular reactivity is considered one of the underlying factors contributing to gender differences in cardiovascular functions and diseases. Experiments were designed to investigate the role of androgens in salt-induced hypertension by assessing the relaxation response of isolated aortic rings to acetylcholine and sodium nitroprusside in the presence or absence of l-nitroarginine methyl ester in Sprague–Dawley rats. The rats were either orchidectomized or sham-operated, with or without testosterone replacement, and were placed on a normal or high-salt diet for 6 weeks. The results indicate a significant increase (p < 0.001) in the mean arterial blood pressure of rats on the high-salt diet, when compared with control or orchidectomized rats. Orchidectomy elicited a reduction in mean arterial blood pressure (p < 0.01), while testosterone replacement normalized mean arterial blood pressure to values seen in intact rats on the high-salt diet. The high-salt diet reduced the relaxation response to acetylcholine both in the presence and absence of inhibition of endothelial nitric oxide synthase with l-nitroarginine methyl ester. Bilateral orchidectomy attenuated the impaired endothelial function induced by the high-salt diet in rats, but this was reversed by concomitant administration of testosterone, suggesting a role for androgens in enhancing long-term vascular smooth muscle tone and hence maintenance of high blood pressure in salt-induced hypertension.

scholarly journals Resuscitation with lactated Ringer solution limits the expression of molecular events associated with lung injury after hemorrhage

2005 ◽  
Vol 98 (2) ◽  
pp. 550-556 ◽  
Author(s):  
Juliann G. Kiang ◽  
Xinyue Lu ◽  
Lindita S. Tabaku ◽  
Timothy B. Bentley ◽  
James L. Atkins ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Lung Injury ◽  
Arterial Blood Pressure ◽  
Mean Arterial Blood Pressure ◽  
Caspase 3 ◽  
Ringer Solution ◽  
Sprague Dawley ◽  
Arterial Blood ◽  
Atp Levels ◽  
Molecular Events

The aim of this study was to determine whether hemorrhage altered the caspase-3 activity and the ATP levels in rat lung and ileum tissues and determine whether resuscitation with lactated Ringer solution (LR) or whole blood (WB) reversed these changes. Male Sprague-Dawley rats were briefly anesthetized with isoflurane, and their mean arterial blood pressure was reduced from 110 to 40 mmHg by bleeding. The bled rat was then resuscitated with LR or autologous WB to bring mean arterial blood pressure back to 80 mmHg. Lung and ileum tissues were removed at the end of hemorrhage or at the end of the resuscitation period for specified bioassays. Hemorrhage increased cellular caspase-3 activity in the lung and the ileum. After the hemorrhaged rats received LR or WB, caspase-3 activity returned to the basal level in the lung and ileum, respectively. Likewise, hemorrhage decreased cellular ATP levels in lung and ileum. After LR or WB resuscitation, the cellular ATP level returned to the basal level only in the lung resuscitated with LR. The increased caspase-3 activity was associated with the increased expression of caspase-3 mRNA, which also returned to normal levels after either resuscitation. Similarly, hemorrhage increased the expression of inducible nitric oxide synthase and Kruppel-like factor 6 and decreased expression of Kruppel-like factor 4. Subsequent LR resuscitation normalized the expression of these genes in the lung tissue. Our results demonstrate that resuscitation with LR can reverse the expression of genes and their products that are thought to contribute to hemorrhage-induced lung injury.

Abstract 446: Rostral Ventrolateral Lateral Medulla Mediates the Sympathetic and Cardiovascular Response to Increased Cerebrospinal Fluid Sodium Concentration

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Sean D Stocker
Keyword(s):  
Blood Pressure ◽  
Arterial Blood Pressure ◽  
Mean Arterial Blood Pressure ◽  
Sympathetic Nerve ◽  
Lateral Ventricle ◽  
Cardiovascular Response ◽  
Sprague Dawley ◽  
Arterial Blood ◽  
Nerve Recordings

Compelling evidence indicates increased cererbrospinal fluid (CSF) sodium elevates sympathetic nerve activity (SNA) and arterial blood pressure (ABP) in salt-sensitive hypertension. RVLM neurons project to the spinal cord and regulate SNA and ABP under a number of physiological challenges and pathophysiological states. Therefore, we hypothesized that RVLM neurons mediate the sympathoexcitatory response to increased CSF sodium. Inactin-anesthetized, male Sprague-Dawley rats (n=5/group) were prepared for sympathetic nerve recordings and a lateral ventricle brain cannula. Infusion of 1M NaCl (5 μL/10 min) to increase CSF sodium concentrations by 5mM produced a significant (P’s<0.05, n=6) increase in lumbar SNA (Δ: 115±3%), adrenal SNA (Δ: 122±3%), and mean arterial blood pressure (Δ: 8±1 mmHg). The infusion did not affect splanchnic SNA (Δ: 102±4%) but decreased renal SNA (Δ: 91±2%). Inhibition of the RVLM with bilateral injection of the GABA agonist muscimol (2.5mM per 50 nL per side) significantly (P’s<0.05; n=5) attenuated the increased lumbar SNA (Δ:101±2%), adrenal SNA (Δ:105±2%), and mean arterial blood pressure (Δ: 1±1mmHg, P’s<0.05; n=6). Blockade of ionotropic glutamate receptors in the RVLM with bilateral injection of kynurenic acid (30mM per 50 nL per side) also significantly (P’s<0.05; n=5) attenuated the increase in lumbar SNA (Δ: 101±3%), adrenal SNA (Δ: 110±3%) and mean ABP (Δ: 1±2 mmHg) to lateral ventricle infusion of 1M NaCl (5uL/10 min). In a final set of experiments, in vivo single-unit recordings demonstrate that ventricular infusion of 1M NaCl (5uL per 10 min) increased discharge in 60% (6/10) of spinally-projecting, barosensitive RVLM neurons (2.1±0.4 to 5.8±0.2 Hz, P<0.05). Infusion of artificial CSF did not affect any variable. These findings suggest increased CSF sodium activates a glutamatergic pathway to RVLM neurons to elevate SNA and ABP.

Cardiovascular effects of atrial extracts in anesthetized rats

1984 ◽  
Vol 62 (7) ◽  
pp. 819-826 ◽  
Author(s):  
Uwe Ackermann ◽  
Terumi G. Irizawa ◽  
Susan Milojevic ◽  
Harald Sonnenberg
Keyword(s):  
Blood Pressure ◽  
Arterial Blood Pressure ◽  
Mean Arterial Blood Pressure ◽  
Cardiovascular Effects ◽  
Hypotensive Effect ◽  
Vagal Afferents ◽  
Sprague Dawley ◽  
Direct Stimulation ◽  
Arterial Blood ◽  
Cardiopulmonary Receptors

Tissue extracts derived from atria or ventricles of Sprague–Dawley rats were injected into Inactin-anesthetized assay rats. Compared with ventricular extracts, atrial extracts produced a 20 mmHg (1 mmHg = 133.322 Pa) fall in mean arterial blood pressure. This fall resulted from failure to increase cardiac output in compensation for peripheral vasodilation. Two factors were responsible: depression of heart rate (by 25 beats/min) and failure to increase cardiac performance. The time patterns and magnitudes of changes in cardiovascular parameters after cardiac extracts were not changed by prior atropinization. However, assay rats that were vagotomized showed no cardiac slowing after atrial extract and showed a significantly smaller decrease in mean arterial blood pressure than did sham-vagotomized or intact rats. Another group of assay rats was vagotomized as well as carotid-sinus-denervated before extract injection. In these rats the degree of hypotension caused by atrial extract was significantly greater than that observed after vagotomy alone and was not significantly different from that observed in rats with intact innervation. The results suggest that the hypotension that is caused by atrial extract, but not by ventricular extracts, results in part from the reflex effects of direct stimulation of chemosensitive cardiopulmonary receptors with vagal afferents and partly from the reflex effects of baroreceptor unloading. Ventricular extract had no hypotensive effect in any group of assay rats.

Physiological elevation in plasma angiotensinogen increases blood pressure

2001 ◽  
Vol 281 (5) ◽  
pp. R1437-R1441 ◽  
Author(s):  
Christoph P. R. Klett ◽  
Joey P. Granger
Keyword(s):  
Blood Pressure ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Arterial Blood Pressure ◽  
Mean Arterial Blood Pressure ◽  
Femoral Vein ◽  
Formation Rate ◽  
Plasma Concentrations ◽  
Sprague Dawley ◽  
Arterial Blood

Hepatic angiotensinogen secretion is controlled by a complex pattern of physiological or pathophysiological mediators. Because plasma concentrations of angiotensinogen are close to the Michaelis-Menten constant, it was hypothesized that changes in circulating angiotensinogen affect the formation rate of ANG I and ANG II and, therefore, blood pressure. To further test this hypothesis, we injected purified rat angiotensinogen intravenously in Sprague-Dawley rats via the femoral vein and measured mean arterial blood pressure after arterial catheterization. In controls, mean arterial pressure was 131 ± 2 mmHg before and after the injection of vehicle (sterile saline). The injection of 0.8, 1.2, and 2.9 mg/kg angiotensinogen caused a dose-dependent increase in mean arterial blood pressure of 8 ± 0.4, 19.3 ± 2.1, and 32 ± 2.4 mmHg, respectively. In contrast, the injection of a purified rabbit anti-rat angiotensinogen antibody (1.4 mg/kg) resulted in a significant decrease in mean arterial pressure (−33 ± 3.2 mmHg). Plasma angiotensinogen increased to 769 ± 32, 953 ± 42, and 1,289 ± 79 pmol/ml, respectively, after substrate and decreased by 361 ± 28 pmol/ml after antibody administration. Alterations in plasma angiotensinogen correlated well with changes in plasma renin activity. In summary, variations in circulating angiotensinogen can result in changes in blood pressure. In contrast to renin, which is known as a tonic regulator for the generation of ANG I, angiotensinogen may be a factor rather important for long-term control of the basal activity of the renin-angiotensin system.

scholarly journals Uninephrectomy reduces 11β-hydroxysteroid dehydrogenase type 1 and type 2 concomitantly with an increase in blood pressure in rats

2012 ◽  
Vol 214 (3) ◽  
pp. 373-380 ◽  
Author(s):  
M Lauterburg ◽  
G Escher ◽  
B Dick ◽  
D Ackermann ◽  
F J Frey
Keyword(s):  
Blood Pressure ◽  
Arterial Blood Pressure ◽  
Mean Arterial Blood Pressure ◽  
Hydroxysteroid Dehydrogenase ◽  
Gas Chromatography Mass Spectrometry ◽  
Sham Operation ◽  
Sprague Dawley ◽  
Arterial Blood

Renal allograft donors are at risk of developing hypertension. Here, we hypothesized that this risk is at least in part explained by an enhanced intracellular availability of 11β-hydroxyglucocorticoids due to an increased 11β-hydroxysteroid dehydrogenase type 1 enzyme (11β-HSD1), an intracellular prereceptor activator of biologically inactive 11-ketocorticosteroids in the liver, and/or a diminished 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), an inactivator of 11β-hydroxyglucocorticoids in the kidney. To test this hypothesis, uninephrectomized (UNX) (n=9) and sham-operated (n=10) adult Sprague–Dawley rats were investigated. Mean arterial blood pressure and heart rate were measured continuously by telemetry for 6 days in week 5 after UNX. The mRNA of11β-Hsd1and11β-Hsd2in liver and kidney tissues were assessed by RT-PCR and the 11β-HSD activities were directly quantified in their corresponding tissues by determining the ratios of (tetrahydrocorticosterone+5α-tetrahydrocorticosterone)/tetrahydrodehydrocorticosterone ((THB+5α-THB)/THA) and of corticosterone/dehydrocorticosterone (B/A) by gas chromatography–mass spectrometry. The apparent total body activities of 11β-HSD1 and 11β-HSD2 were estimated using the urinary and plasma ratios of (THB+5α-THB)/THA and B/A. Mean arterial blood pressure was increased after UNX when compared with sham operation. Hepatic mRNA content of11β-Hsd1and hepatic, plasma, and urinary ratios of (THB+5α-THB)/THA were decreased after UNX, indicating diminished access of glucocorticoids to its receptors. In renal tissue,11β-Hsd2mRNA was reduced and B/A ratios measured in kidney, plasma, and urine were increased, indicating reduced 11β-HSD2 activity and enhanced access of glucocorticoids to mineralocorticoid receptors. Both 11β-HSD1 and 11β-HSD2 are downregulated after UNX in rats, a constellation considered to induce hypertension.

scholarly journals Increased superoxide levels in ganglia and sympathoexcitation are involved in sarafotoxin 6c-induced hypertension

2008 ◽  
Vol 295 (5) ◽  
pp. R1546-R1554 ◽  
Author(s):  
Melissa Li ◽  
Xiaoling Dai ◽  
Stephanie Watts ◽  
David Kreulen ◽  
Gregory Fink
Keyword(s):  
Blood Pressure ◽  
Sympathetic Innervation ◽  
Sympathetic Ganglia ◽  
Plasma Norepinephrine ◽  
Sprague Dawley ◽  
Surgical Ablation ◽  
Arterial Blood ◽  
Sprague Dawley Rats ◽  
Induced Hypertension ◽  
Hypertension Development

Endothelin (ET) type B receptors (ETBR) are expressed in multiple tissues and perform different functions depending on their location. ETBR mediate endothelium-dependent vasodilation, clearance of circulating ET, and diuretic effects; all of these should produce a fall in arterial blood pressure. However, we recently showed that chronic activation of ETBR in rats with the selective agonist sarafotoxin 6c (S6c) causes sustained hypertension. We have proposed that one mechanism of this effect is constriction of capacitance vessels. The current study was performed to determine whether S6c hypertension is caused by increased generation of reactive oxygen species (ROS) and/or activation of the sympathetic nervous system. The model used was continuous 5-day infusion of S6c into male Sprague-Dawley rats. No changes in superoxide anion levels in arteries and veins were found in hypertensive S6c-treated rats. However, superoxide levels were increased in sympathetic ganglia from S6c-treated rats. In addition, superoxide levels in ganglia increased progressively the longer the animals received S6c. Treatment with the antioxidant tempol impaired S6c-induced hypertension and decreased superoxide levels in ganglia. Acute ganglion blockade lowered blood pressure more in S6c-treated rats than in vehicle-treated rats. Although plasma norepinephrine levels were not increased in S6c hypertension, surgical ablation of the celiac ganglion plexus, which provides most of the sympathetic innervation to the splanchnic organs, significantly attenuated hypertension development. The results suggest that S6c-induced hypertension is partially mediated by sympathoexcitation to the splanchnic organs driven by increased oxidative stress in prevertebral sympathetic ganglia.

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