scholarly journals Cyclooxygenase-1 inhibition attenuates angiotensin II-salt hypertension and neurogenic pressor activity in the rat

2013 ◽  
Vol 305 (10) ◽  
pp. H1462-H1470 ◽  
Author(s):  
Ninitha Asirvatham-Jeyaraj ◽  
Andrew J. King ◽  
Carrie A. Northcott ◽  
Shivanshu Madan ◽  
Gregory D. Fink
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Whole Body ◽  
Plasma Norepinephrine ◽  
Ang Ii ◽  
Salt Diet ◽  
Depressor Response ◽  
Cox Inhibitor ◽  
Pressor Activity ◽  
Cox 1

Cyclooxygenase (COX)-derived prostanoids contribute to angiotensin II (ANG II) hypertension (HTN). However, the specific mechanisms by which prostanoids act are unclear. ANG II-induced HTN is caused partly by increased sympathetic nervous system activity, especially in a setting of high dietary salt intake. This study tested the hypothesis that COX-derived prostanoids cause ANG II-salt sympathoexcitation and HTN. Experiments were conducted in conscious rats. Infusion of ANG II (150 ng·kg−1·min−1 sc) caused a marked HTN in rats on 2% salt diet, but a much smaller increase in blood pressure in rats on 0.4% salt diet. The nonselective COX inhibitor ketoprofen (2 mg/kg sc) given throughout the ANG-II infusion period attenuated HTN development in rats on 2% NaCl diet, but not in rats on 0.4% NaCl diet. The acute depressor response to ganglion blockade was used to assess neurogenic pressor activity in rats on 2% NaCl diet. Ketoprofen-treated rats showed a smaller fall in arterial pressure in response to ganglion blockade during ANG-II infusion than did nontreated controls. In additional experiments, ketoprofen-treated rats exhibited smaller increases in plasma norepinephrine levels and whole body norepinephrine spillover than we previously reported in ANG II-salt HTN. Finally, the effects of the selective COX-1 inhibitor SC560 (10 mg·kg−1·day−1 ip) and the selective COX-2 inhibitor nimesulide (10 mg·kg−1·day−1 ip) were investigated. Treatment with SC560 but not nimesulide significantly reduced blood pressure and the depressor response to ganglion blockade in ANG II-salt HTN rats. The results suggest that COX-1 products are critical for sympathoexcitation and the full development of ANG II-salt HTN in rats.

Salt sensitivity in hypertensive rats with angiotensin II administration

1990 ◽  
Vol 259 (5) ◽  
pp. R1012-R1016 ◽  
Author(s):  
K. Ando ◽  
Y. Sato ◽  
T. Fujita
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Salt Sensitivity ◽  
Ang Ii ◽  
Short Term ◽  
Salt Loading ◽  
Salt Diet ◽  
Dose Dependent Fashion ◽  
Dose Dependent

We examined the salt sensitivity of blood pressure in angiotensin II (ANG II)-induced hypertension. Wistar rats, salt loaded (0.66, 2, or 8% salt-containing diet) for 4 or 12 days, were infused intravenously with 15 or 60 ng/min of ANG II. Systolic blood pressure (SBP) was not increased by long-term (12 days) salt loading, and SBP was unchanged with ANG II and normal-salt (0.66%) diet. However, when combined with salt loading, ANG II produced hypertension in a dose-dependent fashion; compared with control (120 +/- 2 mmHg), SBP was increased with 15 ng/min of ANG II and 8% salt diet (145 +/- 5 mmHg, P less than 0.05) and with 60 ng/min of ANG II and either 2 or 8% salt diet (149 +/- 8 and 174 +/- 8 mmHg, P less than 0.05, respectively). Na space (exchangeable Na) was increased in a roughly similar pattern and correlated significantly (r = 0.531, P less than 0.05) with SBP. However, with 15 ng/min of ANG II, Na space was not different among rats on either level of salt loading, although the 8% salt diet elevated SBP. Data obtained with short-term (4 days) treatment indicate that an elevated Na space preceded development of hypertension. With 15 ng/min of ANG II and 8% salt diet for 4 days, Na space was markedly (P less than 0.05) increased, but SBP was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Salt intake and angiotensin II alter microvessel density in the cremaster muscle of normal rats

1992 ◽  
Vol 263 (3) ◽  
pp. H664-H667 ◽  
Author(s):  
I. Hernandez ◽  
A. W. Cowley ◽  
J. H. Lombard ◽  
A. S. Greene
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Microvessel Density ◽  
Salt Intake ◽  
Plasma Renin ◽  
Ang Ii ◽  
Cremaster Muscle ◽  
Salt Diet ◽  
Dose Dependent Increase ◽  
Dose Dependent

This study investigated the effect of salt intake and angiotensin II (ANG II) levels on microvessel density (MVD). Rats with indwelling arterial and venous catheters were placed on either a high-salt (HS; 4%) or a low-salt diet (LS; 0.4%) for 2 or 4 wk, and blood pressure, heart rate, and plasma renin activity were measured. Plasma ANG II was fixed at normal levels in half of the rats on HS by continuous intravenous infusion of ANG II (5 ng.kg-1.min-1). Samples of cremaster muscle were examined histologically to determine MVD. No difference in MVD was observed between HS and LS groups after 2 wk. After 4 wk on HS, MVD was reduced (22.4%, P less than 0.05) compared with the LS group. In rats fed HS, ANG II infusion induced a significant dose-dependent increase in MVD from 85.11 +/- 3.34 to 98.94 +/- 4.62 (ANG II, 5 ng.kg-1.min-1) and to 107.60 +/- 7.00 (ANG II, 10 ng.kg-1.min-1) (P less than 0.05), with no change in blood pressure. Maintenance of ANG II levels for 4 wk blocked the rarefaction due to salt. These results suggest that the decrease in MVD due to salt could be the result of a dietary-induced fall in plasma ANG II levels.

Separation of peripheral and central cardiovascular actions of angiotensin II

1997 ◽  
Vol 273 (6) ◽  
pp. H2620-H2626 ◽  
Author(s):  
Jaspal S. Kooner ◽  
Clive N. May ◽  
Stanley Peart ◽  
Christopher J. Mathias
Keyword(s):  
Blood Pressure ◽  
Nervous System ◽  
Angiotensin Ii ◽  
Sympathetic Nervous System ◽  
Plasma Norepinephrine ◽  
Ang Ii ◽  
Vascular Effects ◽  
Before And After ◽  
Sympathetic Nervous ◽  
Conscious Rabbits

The pressor and vasoconstrictor action of angiotensin II (ANG II) is considered to be caused by a combination of its direct and indirect vascular effects, the latter mediated by the sympathetic nervous system. The purpose of this study was to determine the extent to which the direct and indirect actions of ANG II contribute to its pressor and vascular effects. Blood pressure, cutaneous vascular, and plasma norepinephrine responses to intravenous ANG II were measured in conscious rabbits before and after inhibition of central sympathetic outflow with intravenous and intracisternal clonidine and after ganglionic blockade with intravenous pentolinium. Intravenous ANG II caused a similar dose-related rise in blood pressure before and after sympathetic blockade with intravenous clonidine, intracisternal clonidine, and intravenous pentolinium. In contrast, the dose-related fall in cutaneous ear blood flow and cutaneous ear temperature and rise in cutaneous ear vascular resistance induced by intravenous ANG II were abolished after intravenous clonidine, intracisternal clonidine, and intravenous pentolinium. Heart rate was unchanged after ANG II. There were no changes in back skin or rectal temperature. There was a nonsignificant fall in plasma norepinephrine and no change in epinephrine after ANG II. These results demonstrate that the acute pressor response to intravenous ANG II is mediated by its direct vascular effects and is not dependent on central or ganglionic stimulation of the sympathetic nervous system, in contrast to the effect of ANG II on cutaneous ear vasoconstriction, which is predominantly caused by a centrally mediated increase in sympathetic nervous activity. Our results separate, in conscious rabbits, the direct vascular effects of ANG II from its indirect vascular actions, which are mediated by central sympathetic stimulation in the brain.

scholarly journals Endoplasmic reticulum and oxidant stress mediate nuclear factor-κB activation in the subfornical organ during angiotensin II hypertension

2015 ◽  
Vol 308 (10) ◽  
pp. C803-C812 ◽  
Author(s):  
Colin N. Young ◽  
Anfei Li ◽  
Frederick N. Dong ◽  
Julie A. Horwath ◽  
Catharine G. Clark ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Endoplasmic Reticulum ◽  
Transcription Factor ◽  
Angiotensin Ii ◽  
Er Stress ◽  
Bioluminescence Imaging ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Ang Ii ◽  
Arterial Blood

Endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) generation in the brain circumventricular subfornical organ (SFO) mediate the central hypertensive actions of Angiotensin II (ANG II). However, the downstream signaling events remain unclear. Here we tested the hypothesis that angiotensin type 1a receptors (AT1aR), ER stress, and ROS induce activation of the transcription factor nuclear factor-κB (NF-κB) during ANG II-dependent hypertension. To spatiotemporally track NF-κB activity in the SFO throughout the development of ANG II-dependent hypertension, we used SFO-targeted adenoviral delivery and longitudinal bioluminescence imaging in mice. During low-dose infusion of ANG II, bioluminescence imaging revealed a prehypertensive surge in NF-κB activity in the SFO at a time point prior to a significant rise in arterial blood pressure. SFO-targeted ablation of AT1aR, inhibition of ER stress, or adenoviral scavenging of ROS in the SFO prevented the ANG II-induced increase in SFO NF-κB. These findings highlight the utility of bioluminescence imaging to longitudinally track transcription factor activation during the development of ANG II-dependent hypertension and reveal an AT1aR-, ER stress-, and ROS-dependent prehypertensive surge in NF-κB activity in the SFO. Furthermore, the increase in NF-κB activity before a rise in arterial blood pressure suggests a causal role for SFO NF-κB in the development of ANG II-dependent hypertension.

Abstract MP03: ROCK2 Specific Inhibition Attenuates Angiotensin II-induced Hypertension In Mice

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Daniel J Fehrenbach ◽  
Meena S Madhur
Keyword(s):  
Blood Pressure ◽  
T Cell ◽  
Angiotensin Ii ◽  
Repeated Measures ◽  
Flow Cytometric Analysis ◽  
Coiled Coil ◽  
Ang Ii ◽  
Induced Hypertension

Hypertension, or an elevated blood pressure, is the primary modifiable risk factor for cardiovascular disease, the number one cause of mortality worldwide. We previously demonstrated that Th17 activation and interleukin 17A (IL-17A)/IL-21 production is integral for the full development of a hypertensive phenotype as well as the renal and vascular damage associated with hypertension. Rho-associated coiled-coil containing protein Kinase 2 (ROCK2) serves as a molecular switch upregulating Th17 and inhibiting regulatory T cell (Treg) differentiation. We hypothesize that hypertension is characterized by excessive T cell ROCK2 activation leading to increased Th17/Treg ratios and ultimately end-organ damage. We first showed in vitro that KD025, an experimental orally bioavailable ROCK2 inhibitor inhibits Th17 cell proliferation and IL-17A/IL-21 production. To determine if hypertensive stimuli such as endothelial stretch increases T cell ROCK2 expression, we cultured human aortic endothelial cells exposed to 5% (normotensive) or 10% (hypertensive) stretch with circulating human T cells and HLA-DR+ antigen presenting cells. Hypertensive stretch increased T cell ROCK2 expression 2-fold. We then tested the effect of ROCK2 inhibition with KD025 (50mg/kg i.p. daily) in vivo on angiotensin II (Ang II)-induced hypertension. Treatment with KD025 significantly attenuated the hypertensive response within 1 week of Ang II treatment (systolic blood pressure: 139± 8 vs 108±7mmHg) and this persisted for the duration of the 4 week study reaching blood pressures 20 mmHg lower (135±13mmHg) than vehicle treated mice (158±4mmHg p<0.05 effect of treatment 2-way Repeated Measures ANOVA). Flow cytometric analysis of tissue infiltrating leukocytes revealed that KD025 treatment increased Treg/Th17 ratios in the kidney (0.61±0.03 vs 0.79±0.08, p<0.05 student’s t-test). Thus, T cell ROCK2 may be a novel therapeutic target for the treatment of hypertension.

Comparison of fast and slow pressor effects of angiotensin II in the conscious rat

1981 ◽  
Vol 241 (3) ◽  
pp. H381-H388 ◽  
Author(s):  
A. J. Brown ◽  
J. Casals-Stenzel ◽  
S. Gofford ◽  
A. F. Lever ◽  
J. J. Morton
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Pressor Response ◽  
Control Period ◽  
Urinary Sodium Excretion ◽  
Sodium Balance ◽  
Pressor Effect ◽  
Ang Ii ◽  
Conscious Rat ◽  
Female Wistar Rats

Female Wistar rats were infused intravenously with 5% dextrose for 3 days, then with angiotensin II (ANG II) in 5% dextrose at 20 ng . kg-1 . min-1 for 7 days, and finally with dextrose for 2.5 days. ANG II raised mean arterial pressure (MAP) gradually; by the 7th day it was 49.7 mmHg higher than during the dextrose control period in the same rats. Control rats were infused with dextrose for 12.5 days; MAP did not change. Plasma ANG II concentration was measured during infusion. In hypertensive rats on the 7th day of ANG II infusion, it was six times higher than in control rats infused with dextrose. Changes of blood pressure and plasma ANG II concentration were compared in further rats infused with much larger doses of ANG II. Rats receiving 270 ng . kg-1 . min-1 for 1 h had an almost maximal direct pressor response, MAP rising 45.3 mmHg and plasma ANG II rising 32-fold compared with controls. Thus, infusion of ANG II at low dose without direct pressor effect gradually raises blood pressure to a level similar to the maximum direct pressor effect produced by larger doses of ANG II. Sodium balance and food and water intakes were also measured and did not change during prolonged infusion of ANG II at 20 ng . kg-1 . min-1. Thus, the slow pressure effect of ANG II develops at a lower and more nearly physiological plasma concentration of the peptide than do the direct pressor effect and the effects on drinking, eating, and urinary sodium excretion.

The effects of estradiol and testosterone on renal tissues oxidative after central injection of angiotensin II in female doca – salt treated rats

2018 ◽  
Vol 37 (3) ◽  
Author(s):  
Marzieh Kafami ◽  
Mahmoud Hosseini ◽  
Saeed Niazmand ◽  
Esmaeil Farrokhi ◽  
Mosa Al-Reza Hajzadeh ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Sex Hormones ◽  
Active Oxygen Species ◽  
Oxygen Species ◽  
Research Needs ◽  
Ang Ii ◽  
Detailed Mechanism ◽  
Female Wistar Rats

Abstract Background Although numerous studies have proven that estrogen (Est) has a protective effect on the development of hypertension, more research needs to be done to show its detailed mechanism in a variety of hypertension. The important role of active oxygen species in blood pressure is well defined. We examined whether or not sex hormones change the growth of reactive oxygen species (ROS) ‎in kidneys after central microinjection of angiotensin II (Ang II).‎ Materials and methods Female Wistar rats, 8 weeks old (200 ± 10 g) were used in this study. The animal groups were (1) Sham, (2) Ovariectomy (OVX), (3) Sham-Hypertension (Sham-Hyper), (4) OVX-Hypertension (OVX-Hyper), (5) Sham-Hyper-Est, (6) OVX-Hyper-Est‎;‎ (7) Sham-Hyper-Testosterone (Tst) and (8) OVX-Hyper-Tst. Solutions of 1% NaCl and 0.1 KCl ‎were used and desoxycorticostrone (doca-salt) was injected (45 mg/kg) 3 times a week in Hypertension groups. Estradiol and Tst (2 mg/kg and ‎5 mg/kg‎; daily; subcutaneously) for 4 weeks. Ang II (50 μM, 5 μL) was microinjected by intracerebroventricular ( i.c.v.) infusion and malondialdehyde (MDA) and thiol in the kidneys were measured. Results MDA in the kidneys was increased by Ang II and doca-salt treatments. Both estradiol and Tst decreased the kidney’s MDA. The level of thiol was higher in Hyper ‎groups and reversed after treatment with estradiol and Tst. Conclusions Our findings suggest that central effect of Ang II on blood pressure and kidney ‎disease is accompanied with increased levels of oxidative stress in the kidneys. Indeed sex hormones change the ROS level in the kidneys after central ‎microinjection of Ang II.‎‎

scholarly journals Angiotensin II, Hypercholesterolemia, and Vascular Smooth Muscle Cells: A Perfect Trio for Vascular Pathology

2020 ◽  
Vol 21 (12) ◽  
pp. 4525
Author(s):  
Amanda St. Paul ◽  
Cali B. Corbett ◽  
Rachael Okune ◽  
Michael V. Autieri
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Vascular Smooth Muscle ◽  
Vascular Diseases ◽  
Reduce Blood Pressure ◽  
Vascular Pathology ◽  
Lipid Lowering ◽  
Ang Ii

Cardiovascular disease is the leading cause of morbidity and mortality in the Western and developing world, and the incidence of cardiovascular disease is increasing with the longer lifespan afforded by our modern lifestyle. Vascular diseases including coronary heart disease, high blood pressure, and stroke comprise the majority of cardiovascular diseases, and therefore represent a significant medical and socioeconomic burden on our society. It may not be surprising that these conditions overlap and potentiate each other when we consider the many cellular and molecular similarities between them. These intersecting points are manifested in clinical studies in which lipid lowering therapies reduce blood pressure, and anti-hypertensive medications reduce atherosclerotic plaque. At the molecular level, the vascular smooth muscle cell (VSMC) is the target, integrator, and effector cell of both atherogenic and the major effector protein of the hypertensive signal Angiotensin II (Ang II). Together, these signals can potentiate each other and prime the artery and exacerbate hypertension and atherosclerosis. Therefore, VSMCs are the fulcrum in progression of these diseases and, therefore, understanding the effects of atherogenic stimuli and Ang II on the VSMC is key to understanding and treating atherosclerosis and hypertension. In this review, we will examine studies in which hypertension and atherosclerosis intersect on the VSMC, and illustrate common pathways between these two diseases and vascular aging.

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