scholarly journals New Therapeutic Insight into the Effect of Ma Huang Tang on Blood Pressure and Renal Dysfunction in the L-NAME-Induced Hypertension

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Mi Hyeon Hong ◽  
Hye Yoom Kim ◽  
Youn Jae Jang ◽  
Se Won Na ◽  
Byung Hyuk Han ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Renal Function ◽  
Intima Media Thickness ◽  
Dependent Manner ◽  
Vascular Relaxation ◽  
Sprague Dawley ◽  
Induced Hypertension ◽  
Ma Huang

In this study, we evaluated the effect of a traditional herbal formula, Ma Huang Tang (MHT), on blood pressure and vasodilation in a rat model of NG‐nitro‐L‐arginine methylester- (L-NAME-) induced hypertension. We found that MHT-induced vascular relaxation in a dose-dependent manner in rat aortas pretreated with phenylephrine. However, pretreatment of endothelium-intact aortic rings with L‐NAME, an inhibitor of nitric oxide synthesis (NOS), or 1H‐[1, 2, 4]‐oxadiazole‐[4, 3‐α]‐quinoxalin‐1‐one (ODQ), an inhibitor of soluble guanylyl cyclase, significantly abolished vascular relaxation induced by MHT. MHT also increased the production of guanosine 3′,5′-cyclic monophosphate (cGMP) in the aortic rings pretreated with L-NAME or ODQ. To examine the in vivo effects of MHT, Sprague Dawley rats were treated with 40 mg/kg/day L-NAME for 3 weeks, followed by administration of 50 or 100 mg/kg/day MHT for 2 weeks. MHT was found to significantly normalize systolic blood pressure and decreased intima-media thickness in aortic sections of rats treated with L-NAME compared to that of rats treated with L-NAME alone. MHT also restored the L-NAME-induced decrease in vasorelaxation response to acetylcholine and endothelial nitric oxide synthase (eNOS) and endothelin-1 (ET-1) expression. Furthermore, MHT promoted the recovery of renal function, as indicated by osmolality, blood urea nitrogen (BUN) levels, and creatinine clearance. These results suggest that MHT-induced relaxation in the thoracic aorta is associated with activation of the nitric oxide/cGMP pathway. Furthermore, it provides new therapeutic insights into the regulation of blood pressure and renal function in hypertensive patients.

Abstract 71: Novel Bach1 Modulators Increase HMOX1 and Suppress Hypertension in the Goldblatt Model of Renovascular Hypertension

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Matthew Kostura ◽  
Otis Attucks ◽  
Jareer Kassis ◽  
Suparna Gupta ◽  
Samuel Victory ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Enzyme Activity ◽  
Renovascular Hypertension ◽  
Transcriptional Repressor ◽  
Plasma Aldosterone ◽  
Lung Fibroblasts ◽  
Left Renal Artery ◽  
Dependent Manner ◽  
Sprague Dawley

We report for the first time a novel class of compounds that specifically modulate the Bach1 transcriptional repressor pathway. In cellula, the compounds selectively inhibit the activity of the transcriptional repressor Bach1 resulting in transcription of a network of antioxidant and cytoprotective genes including HMOX1. HPP-1971, a member of this class, is a potent and selective Bach1 inhibitor that induces HMOX1 > 40-fold with a potency of 408 nM in human lung fibroblasts. To assess activity in vivo, we tested HPP-1971 in the Goldblatt model of renovascular hypertension. Sprague Dawley rats were implanted with in dwelling pressure telemeter probes and subsequently underwent sham surgery or placement of a 0.25 mm silver clip around the left renal artery. HPP-1971 treatment, dosed orally at 1,3,10 and 30 mpk, commenced three days following clip surgery, and continued for 18 days. At study completion, blood pressure, clipped kidney weight, renal HMOX1 enzyme activity and plasma aldosterone levels were measured (see Table). HPP-1971 attenuated both kidney atrophy and the increase in blood pressure in a dose dependent manner with significant differences seen at 3, 10 and 30 mpk (p<.0001). HMOX1 enzyme activity in the clipped kidney increased with treatment, reaching a maximum of 5.7 ± 0.9 nM/hr/mg at 30 mpk relative to sham operated animals (p<.0001). Plasma aldosterone levels increased in 2K1C animals compared to sham controls but were reduced by HPP-1971 treatment. These findings define a novel role for Bach1 suppressors in counteracting the influence of the RAAS system on hypertension and kidney atrophy in the 2K1C model of renovascular hypertension.

Effect of a new mineralocorticoid antagonist mespirenone on aldosterone-induced hypertension

1991 ◽  
Vol 260 (2) ◽  
pp. E269-E271
Author(s):  
J. Opoku ◽  
M. Kalimi ◽  
M. Agarwal ◽  
D. Qureshi
Keyword(s):  
Olive Oil ◽  
Experimental Period ◽  
The Body ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Control Value ◽  
Sprague Dawley Rats ◽  
Mineralocorticoid Antagonist ◽  
Induced Hypertension

The effects of the mineralocorticoid antagonist mespirenone on the development and maintenance of aldosterone-induced hypertension in Sprague-Dawley rats has been studied. Uninephrectomized saline-drinking male Sprague-Dawley rats were injected with either 0.2 ml olive oil, 50 g aldosterone, 1 mg mespirenone, 50 g aldosterone plus 500 g mespirenone, or 50 g aldosterone plus 1 mg mespirenone, each dissolved in 0.2 ml olive oil. Administration of aldosterone alone significantly increased the systolic blood pressure (SBP) from a control value of 114 +/- 3.6 to 162 +/- 4 mmHg by the end of the 3-wk experimental period. Mespirenone given alone had no effect on SBP. However, mespirenone given in combination with aldosterone reversed the hypertension caused by aldosterone in a dose-dependent manner. Saline consumption and urinary output were slightly increased in aldosterone-treated rats compared with the other groups, but the body and organ weights were comparable in all groups. Microscopic examination of kidney and heart showed no abnormalities due to mespirenone. These results suggest that in vivo administration of mespirenone to Sprague-Dawley rats effectively prevents the aldosterone-induced hypertension.

Abstract 105: Therapeutic Suppression of Mtorc2 Signaling Reduces Salt-induced Hypertension and Kidney Injury in SS Rats

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Vikash Kumar ◽  
Loiuse Evans ◽  
Clayton Wollner ◽  
Theresa Kurth ◽  
Allen W Cowley
Keyword(s):  
Blood Pressure ◽  
Renal Cortex ◽  
Kidney Injury ◽  
Salt Sensitivity ◽  
Sprague Dawley ◽  
Urine Albumin ◽  
Sd Rats ◽  
Excess Production ◽  
Induced Hypertension

The present study explored the protective effect of mTORC2 inhibition in salt-induced hypertension and kidney injury. We have previously reported that enhanced blood pressure salt-sensitivity with renal chronic interstitial infusion of H 2 O 2 (347 nmol/kg/min) in normotensive Sprague Dawley (SD) rats. In the present study, in vivo experiment was performed in which H 2 O 2 (347 nmol/Kg/min) was chronically infused for 3 days into renal interstitium of unilaterally nephrectomized SD rats. A significant increase of mTORC2 activity (pAKT/AKT) was observed in the renal cortex of SD rats infused with H 2 O 2 compared to saline infused rats. We have recently shown that excess production of H 2 O 2 in the SS rat kidneys is the hallmark of salt-induced hypertension. We hypothesized that mTORC2 in the kidney contributes to the development of salt-induced hypertension in SS rats. Rats were treated with PP242 which is an ATP-competitor inhibitor which inhibits the activities of both mTORC1 and mTORC2 whereas rapamycin specifically inhibits mTORC1. PP242 was administrated daily (i.p., 15 mg/Kg/day) for 21 days to SS rats fed a 4.0% NaCl diet. Remarkably, salt-induced hypertension was significantly reduced in SS rats which averaged 119 ± 2 mmHg in PP242 treated rats (n=7) compared to 168 ± 3 mmHg in vehicle treated rats (n=7). Albuminuria was greatly reduced with urine albumin excretion (mg/day) averaging 32.8 ± 3 in PP242 treated rats compared to 256 ± 37 in vehicle treated rats. PP242 treatment notably resulted in reduced infiltration of T lymphocytes in the kidneys of SS rats fed a 4.0% NaCl diet. CD3 + cells/mm 2 averaging 157.0 ± 40.0 compared to 36.0 ± 11.0 in the renal cortex and 218.0 ± 24.0 compared to 24.0 ± 9.0 in the outer medulla in PP242 versus vehicle treated rats. These data show that mTORC2 is required for the intiation of salt-induced hypertension and therapeutic suppression of this pathway virtually abolished salt-sensitivity blood pressure and kidney injury.

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.

scholarly journals Phaseolin Attenuates Lipopolysaccharide-Induced Inflammation in RAW 264.7 Cells and Zebrafish

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 420
Author(s):  
Su-Jung Hwang ◽  
Ye-Seul Song ◽  
Hyo-Jong Lee
Keyword(s):  
Nitric Oxide ◽  
Nuclear Translocation ◽  
Raw 264.7 Cells ◽  
Network Pharmacology ◽  
Raw 264.7 ◽  
Dependent Manner ◽  
Bioactive Constituents

Kushen (Radix Sophorae flavescentis) is used to treat ulcerative colitis, tumors, and pruritus. Recently, phaseolin, formononetin, matrine, luteolin, and quercetin, through a network pharmacology approach, were tentatively identified as five bioactive constituents responsible for the anti-inflammatory effects of S. flavescentis. However, the role of phaseolin (one of the primary components of S. flavescentis) in the direct regulation of inflammation and inflammatory processes is not well known. In this study, the beneficial role of phaseolin against inflammation was explored in lipopolysaccharide (LPS)-induced inflammation models of RAW 264.7 macrophages and zebrafish larvae. Phaseolin inhibited LPS-mediated production of nitric oxide (NO) and the expression of inducible nitric oxide synthase (iNOS), without affecting cell viability. In addition, phaseolin suppressed pro-inflammatory mediators such as cyclooxygenase 2 (COX-2), interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and interleukin-6 (IL-6) in a dose-dependent manner. Furthermore, phaseolin reduced matrix metalloproteinase (MMP) activity as well as macrophage adhesion in vitro and the recruitment of leukocytes in vivo by downregulating Ninjurin 1 (Ninj1), an adhesion molecule. Finally, phaseolin inhibited the nuclear translocation of nuclear factor-kappa B (NF-κB). In view of the above, our results suggest that phaseolin could be a potential therapeutic candidate for the management of inflammation.

Effects of NG-nitro-L-arginine methyl ester on renal function and blood pressure

1991 ◽  
Vol 261 (6) ◽  
pp. F1033-F1037 ◽  
Author(s):  
V. Lahera ◽  
M. G. Salom ◽  
F. Miranda-Guardiola ◽  
S. Moncada ◽  
J. C. Romero
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Renal Function ◽  
Methyl Ester ◽  
Renal Plasma Flow ◽  
Urinary Sodium Excretion ◽  
Systemic Blood Pressure ◽  
Synthesis Inhibitor ◽  
Renal Changes ◽  
Dose Dependent

The dose-dependent effects of intravenous infusions of nitric oxide (NO) synthesis inhibitor, NG-nitro-L-arginine methyl ester (L-NAME; 0.1, 1, 10, and 50 micrograms.kg-1.min-1), were studied in anesthetized rats to determine whether the inhibitory actions of L-NAME are manifested primarily in alterations of renal function or whether they are the consequences of the increase in systemic blood pressure. Mean arterial pressure (MAP) was not altered by the intravenous L-NAME infusions of 0.1 and 1.0 microgram.kg-1.min-1. However, 0.1 microgram.kg-1.min-1 L-NAME induced a 30% decrease in urine flow rate (UV). The administration of 1.0 microgram.kg-1.min-1 L-NAME, in addition to decreasing UV, also decreased urinary sodium excretion (UNaV) and renal plasma flow (RPF). The intravenous L-NAME infusions of 10.0 and 50.0 microgram.kg-1.min-1 intravenous L-NAME infusions of 10.0 and 50.0 microgram.kg-1.min-1 produced significant increases in MAP that reversed the initial fall in UV and UNaV, despite decreasing RPF and glomerular filtration rate (GFR). The administration of L-arginine alone (10 micrograms.kg-1.min-1) did not modify any of the parameters measured, but it effectively prevented all the hemodynamic and renal changes induced by the infusion of 50 micrograms.kg-1.min-1 L-NAME. These results suggest that the decrease in nitric oxide production induced by the intravenous infusion of L-NAME affects renal excretion of sodium and water in the absence of any significant change in blood pressure. At larger doses, L-NAME also produces hypertension that overrides the initial antinatriuretic effect.

Effect of magnesium supplementation on blood pressure and vascular reactivity in nitric oxide synthase inhibition-induced hypertension model

2015 ◽  
Vol 37 (8) ◽  
pp. 633-642 ◽  
Author(s):  
Filiz Basralı ◽  
Günnur Koçer ◽  
Pınar Ülker Karadamar ◽  
Seher Nasırcılar Ülker ◽  
Leyla Satı ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Nitric Oxide Synthase ◽  
Vascular Reactivity ◽  
Magnesium Supplementation ◽  
Induced Hypertension ◽  
Oxide Synthase

Vagally mediated, nonparacrine effects of cholecystokinin-8s on rat pancreatic exocrine secretion

2007 ◽  
Vol 293 (2) ◽  
pp. G493-G500 ◽  
Author(s):  
Eddy Viard ◽  
Zhongling Zheng ◽  
Shuxia Wan ◽  
R. Alberto Travagli
Keyword(s):  
Brain Stem ◽  
Protein Secretion ◽  
Exocrine Secretion ◽  
Vagal Afferents ◽  
Dependent Manner ◽  
Pancreatic Exocrine Secretion ◽  
Sprague Dawley ◽  
Pancreatic Exocrine ◽  
Vagal Afferent

Cholecystokinin (CCK) has been proposed to act in a vagally dependent manner to increase pancreatic exocrine secretion via actions exclusively at peripheral vagal afferent fibers. Recent evidence, however, suggests the CCK-8s may also affect brain stem structures directly. We used an in vivo preparation with the aims of 1) investigating whether the actions of intraduodenal casein perfusion to increase pancreatic protein secretion also involved direct actions of CCK at the level of the brain stem and, if so, 2) determining whether, in the absence of vagal afferent inputs, CCK-8s applied to the dorsal vagal complex (DVC) can also modulate pancreatic exocrine secretion (PES). Sprague-Dawley rats (250–400 g) were anesthetized and the common bile-pancreatic duct was cannulated to collect PES. Both vagal deafferentation and pretreatment with the CCK-A antagonist lorglumide on the floor of the fourth ventricle decreased the casein-induced increase in PES output. CCK-8s microinjection (450 pmol) in the DVC significantly increased PES; the increase was larger when CCK-8s was injected in the left side of the DVC. Protein secretion returned to baseline levels within 30 min. Microinjection of CCK-8s increased PES (although to a lower extent) also in rats that underwent complete vagal deafferentation. These data indicate that, as well as activating peripheral vagal afferents, CCK-8s increases pancreatic exocrine secretion via an action in the DVC. Our data suggest that the CCK-8s-induced increases in PES are due mainly to a paracrine effect of CCK; however, a relevant portion of the effects of CCK is due also to an effect of the peptide on brain stem vagal circuits.

Abstract 16443: Effects of Dietary Salt Intakes on Blood Pressure, Renal Function and Oxidative Stress in Rats Treated With Candesartan

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Gangyi Zhu ◽  
Yanting Yu ◽  
Xiaoyan Wang
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Renal Function ◽  
Kidney Diseases ◽  
Sprague Dawley ◽  
Dietary Salt ◽  
Salt Restriction ◽  
Low Salt ◽  
Receptor Blockers ◽  
And Oxidative Stress

Candesartan is one of angiotensin II type1 receptor blockers(ARB) and commonly used as first-line antihypertensive treatment. Low salt diet is often recommended by clinicians to the patients with hypertension and kidney diseases. However,it is not clear whether salt restriction is beneficial to the patients taking ARB. In order to explore this problem, the impacts of different salt diets on blood pressure (BP),renal function and oxidative stress were determined in 2-3 months old male Sprague Dawley rats treated with candesartan. The rats were randomly divided into 4 groups fed agar-gelled food rationally with NaCl content at 0.01%, 0.8%, 2% and 4% respectively(4-7 rats/group) while all rats were intraperitoneally injected with candesartan at 1mg / kg / day for 7 days. SBP started to decline on day 2 in all except 4% NaCl groups relative to day 0 (recorded 5-6 hrs before the first injection). On day 6, systolic BP (mmHg, tail-cuff, Softron,BP-98A) was lower in 0.8% (103.7+2.3) & 0.01% (101.6+3) groups than 2% (113.5+4.1) & 4% (129.9+4.6) groups (one way ANOVA,LSD test, P<0.05) and correlated positively with food NaCl intakes (R 2 =0.9832). DBP was changed in a similar pattern as SBP. Serum creatinine (μmol/L) was higher in 0.01% group (225+39) than groups of 0.8% (1328+350), 2% (2095+242) and 4% (1576+703) while creatinine clearance (ml/day) was lower in 0.01% group (69.3+9) than groups of 0.8% (43.7+9), 2%(27.7+2) and 4%(29+0.6). In order to determine whether oxidative stress plays any role in the BP regulation and renal function maintenance, we also checked renal protein expression of ROS components. Relative to 0.8% group, renal NOXs were not altered in 0.01% group while NOX1 (145+18,% of 0.8% group), NOX2 (240+54) and NOX4 (197+41) was higher in 2% group than other groups. Mn-SOD (77+7.8), not Cu-Zn SOD, was decreased while HO1 (170+16), not HO2, was increased in 0.01% group. Renal abundance of nitrotyrosine was lower in 0.01% than other groups indicating a decreased oxidative stress, possibly caused by increase in HO1. We concluded that salt restriction with candesartan is beneficial to antihypertensive effect of AT1R blockade but disadvantage to maintenance of renal function. Thus, cautions to choice of low salt intakes are necessary when taking ARB agents.

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