Hypertension and alterations in central catecholamines after preoptic recess lesions

1989 ◽  
Vol 256 (2) ◽  
pp. R487-R493
Author(s):  
J. W. Van Huysse ◽  
S. L. Bealer
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Parietal Cortex ◽  
Third Ventricle ◽  
Brain Regions ◽  
In Vivo Microdialysis ◽  
Hypothalamic Nucleus ◽  
Per Se

Catecholamine concentrations were measured in brain regions of rats with lesions of the anteroventral third ventricle (AV3V-X rats) or parietal cortex (CORT-X) and of control-operated (CONT) rats. Three hours after surgery, total norepinephrine (NE) concentrations in all brain regions measured of AV3V-X rats were less than those of CONT or CORT-X rats. Epinephrine (EPI) concentrations were decreased in the medulla and hypothalamus, but dopamine levels were unchanged. Also, extracellular NE concentration, estimated by in vivo microdialysis techniques, was increased in the anterior hypothalamic nucleus (AHNE) and dorsomedial medulla (DMMNE) of AV3V-X rats compared with CONT rats. Increased DMMNE paralleled blood pressure increases. DMMNE did not change after blood pressure was increased by intravenous angiotensin II infusion (60 ng/min) in CONT rats. Thus 1) AV3V lesions result in decreased NE and EPI concentrations in multiple brain regions; 2) acute reductions in central NE in AV3V-X rats are associated with increased extracellular NE in the AH and DMM, suggesting increased NE release; and 3) although increased DMMNE is temporally related to increased blood pressure following AV3V lesions, increased DMMNE is not a response to the hypertension per se.

NE turnover in genetically hypertensive rats of Lyon strain. I. Brain nuclei

1988 ◽  
Vol 255 (4) ◽  
pp. H729-H735 ◽  
Author(s):  
M. Sautel ◽  
J. Sacquet ◽  
M. Vincent ◽  
J. Sassard
Keyword(s):  
Blood Pressure ◽  
Hypothalamic Nucleus ◽  
Primary Role ◽  
Hypertensive Rats ◽  
Brain Areas ◽  
Brain Nuclei ◽  
Genetically Hypertensive Rats ◽  
Low Blood Pressure ◽  
Genetically Hypertensive

Several indirect evidences of alterations in the central catecholaminergic structures were obtained in genetically hypertensive rats. Because they could be of pathogenetic value, we measured, in the present work, the in vivo turnover (TO) of norepinephrine (NE) in brain areas of 5- and 22-wk-old genetically hypertensive (LH) rats of the Lyon strain, and their simultaneously selected normotensive (LN) and low blood pressure (LL) controls. Among the changes observed, the increased TO of NE in the A2 and A6 regions of 5-wk-old LH rats and its decrease in the posteroventral hypothalamic nucleus of 22-wk-old LH animals appeared likely to compensate for hypertension. On the contrary, the decreased TO of NE in the anterior hypothalamic nucleus observed at 5 wk and in the A6 and A1 areas at 22 wk of age in LH rats could participate in the development or the maintenance of hypertension. Above all, it was postulated that the increased TO of NE found in the A7 region of 5-wk-old LH rats could play a primary role in the pathogenesis of hypertension in the Lyon model.

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.

scholarly journals Deletion of proton-sensing receptor GPR4 associates with lower blood pressure and lower binding of angiotensin II receptor in SFO

2016 ◽  
Vol 311 (6) ◽  
pp. F1260-F1266 ◽  
Author(s):  
Xuming Sun ◽  
Ellen Tommasi ◽  
Doris Molina ◽  
Renu Sah ◽  
K. Bridget Brosnihan ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Fractional Excretion ◽  
Urine Osmolality ◽  
Brain Regions ◽  
Lower Blood Pressure ◽  
Angiotensin Ii Receptor ◽  
Lower Blood ◽  
Fractional Excretion Of Sodium ◽  
The Impact

Diets rich in grains and meat and low in fruits and vegetables (acid-producing diets) associate with incident hypertension, whereas vegetarian diets associate with lower blood pressure (BP). However, the pathways that sense and mediate the effects of acid-producing diets on BP are unknown. Here, we examined the impact of the deletion of an acid sensor GPR4 on BP. GPR4 is a proton-sensing G protein-coupled receptor and an acid sensor in brain, kidney, and blood vessels. We found that GPR4 mRNA was higher in subfornical organ (SFO) than other brain regions. GPR4 protein was abundant in SFO and present in capillaries throughout the brain. Since SFO partakes in BP regulation through the renin-angiotensin system (RAS), we measured BP in GPR4−/− and GPR4+/+ mice and found that GPR4 deletion associated with lower systolic BP: 87 ± 1 mmHg in GPR4−/− ( n = 35) vs. 99 ± 2 mmHg ( n = 29) in GPR4+/+; P < 0.0001, irrespective of age and sex. Angiotensin II receptors detected by 125I-Sarthran binding were lower in GPR4−/− than GPR4+/+ mice in SFO and in paraventricular nucleus of hypothalamus. Circulating angiotensin peptides were comparable in GPR4−/− and GPR4+/+ mice, as were water intake and excretion, serum and urine osmolality, and fractional excretion of sodium, potassium, or chloride. A mild metabolic acidosis present in GPR4−/− mice did not associate with elevated BP, implying that deficiency of GPR4 may preclude the effect of chronic acidosis on BP. Collectively, these results posit the acid sensor GPR4 as a novel component of central BP control through interactions with the RAS.

Abstract 39: Adrenal ßArrestin1 Raises Serum Aldosterone Levels And Blood Pressure, Both Significant Stroke Risk Factors, In Experimental Rats And Mice

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Anastasios Lymperopoulos ◽  
Ashley Bathgate ◽  
Norma C Salazar
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Gene Delivery ◽  
Adrenal Cortex ◽  
Stroke Risk ◽  
Fluorescent Protein ◽  
Serum Aldosterone ◽  
Increased Risk ◽  
In Vivo Gene Delivery

Introduction: It is widely accepted nowadays that elevation of serum levels of aldosterone, a mineralocorticoid hormone with toxic effects in several cardiovascular tissues, including the heart and cerebral blood vessels, can significantly raise stroke risk. The success of mineralocorticoid receptor blockers, such as eplerenone, at preventing stroke attacks attests to this. Aldosterone is normally produced and secreted by the adrenal cortex in response to angiotensin II. We recently reported that adrenal βarrestin1 (βarr1) plays a crucial role in the physiological angiotensin II-stimulated aldosterone production in the adrenal cortex, leading to marked elevation of circulating serum aldosterone levels in vivo (Lymperopoulos A. et al., Proc. Natl. Acad. Sci. USA. 2009;106:5825-5830). Hypothesis: Herein, we examined the potential impact of this adrenal βarr1-dependent aldosterone elevation on stroke risk in experimental animals in vivo. Methods: We used the βarr1 knockout (βarr1KO) mouse model, studying it alongside wild type (WT) control mice, and also adult male Sprague-Dawley rats, in which adrenal βarr1 was overexpressed in vivo via adrenal-targeted adenoviral-mediated βarr1 gene transfer. Serum aldosterone was measured by ELISA and blood pressure via telemetry. Results: Serum aldosterone at 7 days post-in vivo gene delivery was markedly elevated in adrenal βarr1-overexpressing rats (536+50 pg/ml), compared to control rats receiving the green fluorescent protein (GFP) adenoviral transgene (235+40 pg/ml, p<0.05, n=5). This translated to a significant increase in mean arterial pressure of the βarr1-overexpressing rats (155+5 mmHg) compared to control GFP-expressing rats (137+8 mmHg, p<0.05, n=5), again at 7 days post-in vivo gene delivery, which was prevented by concurrent eplerenone treatment. In contrast, βarr1KO mice had significantly lower serum aldosterone levels (270+20 pg/ml) compared to WT controls (498+35 pg/ml, p<0.05, n=5), at 4 weeks post-experimental myocardial infarction. Conclusions: Adrenal βarr1 up-regulation can dramatically increase circulating aldosterone levels and systemic blood pressure, thus conferring increased risk for stroke in experimental rodents.

In vitro and in vivo inhibition of renin by fatty acids.

1978 ◽  
Vol 234 (6) ◽  
pp. E593 ◽  
Author(s):  
T A Kotchen ◽  
W J Welch ◽  
R T Talwalkar
Keyword(s):  
Blood Pressure ◽  
Fatty Acids ◽  
Linoleic Acid ◽  
Angiotensin Ii ◽  
Neutral Lipids ◽  
Pressor Response ◽  
Arterial Blood ◽  
Arachidonic Acids

Circulating neutral lipids inhibit the in vitro renin reaction. To identify the inhibitor(s), free fatty acids were added to human renin and homologous substrate. Capric, lauric, palmitoleic, linoleic, and arachidonic acids each inhibited the rate of angiotensin I production in vitro (P less than 0.01). Inhibition by polysaturated fatty acids (linoleic and arachidonic) was less (P less than 0.01) after catalytic hydrogenation of the double bonds. To evaluate an in vivo effect of renin inhibition intra-arterial blood pressure responses to infusions of renin and angiotensin II (5.0 microgram) were measured in anephric rats (n = 6) before and after infusion of linoleic acid (10 mg iv). Mean increase of blood pressure to angiotensin II before (75 mmHg +/- 9) and after (90 +/- 12) linoleic acid did not differ (P greater than 0.05). However, the pressor response to renin after linoleic acid (18 +/- 3) was less (P less than 0.00)) than that before (102 +/- 13). In summary, several fatty acids inhibit the in vitro renin reaction, and in part inhibition is dependent on unsaturation. Linoleic acid also inhibits the in vivo pressor response to renin. These results suggest that fatty acids may modify the measurement of plasma renin activity and may also affect angiotensin production in vivo.

scholarly journals Autophagy inhibition by chloroquine prevents increase in blood pressure and preserves endothelial functions

2020 ◽  
Vol 19 (4) ◽  
pp. 789-796
Author(s):  
Moon Jain ◽  
Hina Iqbal ◽  
Pankaj Yadav ◽  
Himalaya Singh ◽  
Debabrata Chanda ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cell Migration ◽  
Endothelial Cell ◽  
Angiotensin Ii ◽  
Ang Ii ◽  
Hypertensive Rats ◽  
Autophagy Flux ◽  
Endothelial Functions

Purpose: To determine the effects of lysosomal inhibition of autophagy by chloroquine (CHQ) onhypertension-associated changes in the endothelial functions. Method: Angiotensin II (Ang II)-treated human endothelial cell line EA.hy926 and renovascularhypertensive rats were subjected to CHQ treatment (in vitro: 0.5, 1, and 2.5 μM; in vivo: 50 mg/kg/dayfor three weeks). Changes in the protein expressions of LC3b II (autophagosome formation marker) andp62 (autophagy flux marker) were assessed using immunoblotting. Cell migration assay, tubuleformation assay (in vitro), and organ bath studies (in vivo) were performed to evaluate the endothelialfunctions. Hemodynamic parameters were measured as well. Results: A higher expression of LC3b II and a reduced expression of p62 observed in the Ang II-treatedendothelial cells, as well as in the aorta of the hypertensive rats, indicated enhanced autophagy.Treatment with CHQ resulted in reduced autophagy flux (in vitro as well as in vivo) and suppressed AngII-induced endothelial cell migration and angiogenesis (in vitro). The treatment with CHQ was alsoobserved to prevent increase in blood pressure in hypertensive rats and preserved acetylcholineinducedrelaxation in phenylephrine-contracted aorta from the hypertensive rats. In addition, chloroquineattenuated Ang II-induced contractions in the aorta of normotensive as well as hypertensive rats. Conclusion: These observations indicated that CHQ lowers the blood pressure and preserves thevascular endothelial function during hypertension. Keywords: Angiotensin II, Autophagy, Chloroquine, Endothelial function, Hypertension, Vasculardysfunction

Angiotensin II-induced hypertrophy is potentiated in mice overexpressing p22phox in vascular smooth muscle

2005 ◽  
Vol 288 (1) ◽  
pp. H37-H42 ◽  
Author(s):  
David S. Weber ◽  
Petra Rocic ◽  
Adamantios M. Mellis ◽  
Karine Laude ◽  
Alicia N. Lyle ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Vascular Smooth Muscle ◽  
In Vivo Model ◽  
Ros Generation ◽  
Ang Ii ◽  
Vascular Hypertrophy ◽  
Wall Area

Increased reactive oxygen species (ROS) are implicated in several vascular pathologies associated with vascular smooth muscle hypertrophy. In the current studies, we utilized transgenic (Tg) mice (Tg p22smc) that overexpress the p22 phox subunit of NAD(P)H oxidase selectively in smooth muscle. These mice have a twofold increase in aortic p22 phox expression and H2O2 production and thus provide an excellent in vivo model in which to assess the effects of increased ROS generation on vascular smooth muscle cell (VSMC) function. We tested the hypothesis that overexpression of VSMC p22 phox potentiates angiotensin II (ANG II)-induced vascular hypertrophy. Male Tg p22smc mice and negative littermate controls were infused with either ANG II or saline for 13 days. Baseline blood pressure was not different between control and Tg p22smc mice. ANG II significantly increased blood pressure in both groups, with this increase being slightly exacerbated in the Tg p22smc mice. Baseline aortic wall thickness and cross-sectional wall area were not different between control and Tg p22smc mice. Importantly, the ANG II-induced increase in both parameters was significantly greater in the Tg p22smc mice compared with control mice. To confirm that this potentiation of vascular hypertrophy was due to increased ROS levels, additional groups of mice were coinfused with ebselen. This treatment prevented the exacerbation of hypertrophy in Tg p22smc mice receiving ANG II. These data suggest that although increased availability of NAD(P)H oxidase-derived ROS is not a sufficient stimulus for hypertrophy, it does potentiate ANG II-induced vascular hypertrophy, making ROS an excellent target for intervention aimed at reducing medial thickening in vivo.

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