scholarly journals Effect of intracerebroventricular benzamil on cardiovascular and central autonomic responses to DOCA-salt treatment

2010 ◽  
Vol 299 (6) ◽  
pp. R1500-R1510 ◽  
Author(s):  
Joanna M. Abrams ◽  
William C. Engeland ◽  
John W. Osborn
Keyword(s):  
Neural Activity ◽  
Sympathetic Activity ◽  
Supraoptic Nucleus ◽  
Salt Treatment ◽  
Salt Hypertension ◽  
Premotor Neurons ◽  
Study Completion ◽  
The Brain ◽  
Regulatory Sites

DOCA-salt treatment increases mean arterial pressure (MAP), while central infusion of benzamil attenuates this effect. The present study used c-Fos immunoreactivity to assess the role of benzamil-sensitive proteins in the brain on neural activity following chronic DOCA-salt treatment. Uninephrectomized rats were instrumented with telemetry transmitters for measurement of MAP and with an intracerebroventricular (ICV) cannula for benzamil administration. Groups included rats receiving DOCA-salt treatment alone, rats receiving DOCA-salt treatment with ICV benzamil, and appropriate controls. At study completion, MAP in vehicle-treated DOCA-salt rats reached 142 ± 4 mmHg. In contrast DOCA-salt rats receiving ICV benzamil had lower MAP (124 ± 3 mmHg). MAP in normotensive controls was 102 ± 3 mmHg. c-Fos immunoreactivity was quantified in the supraoptic nucleus (SON) and across subnuclei of the hypothalamic paraventricular nucleus (PVN), as well as other cardiovascular regulatory sites. Compared with vehicle-treated normotensive controls, c-Fos expression was increased in the SON and all subnuclei of the PVN, but not in other key autonomic nuclei, such as the rostroventrolateral medulla. Moreover, benzamil treatment decreased c-Fos immunoreactivity in the SON and in medial parvocellular and posterior magnocellular neurons of the PVN in DOCA-salt rats but not areas associated with regulation of sympathetic activity. Our results do not support the hypothesis that DOCA-salt increases neuronal activity (as indicated by c-Fos immunoreactivity) of other key regions that regulate sympathetic activity. These results suggest that ICV benzamil attenuates DOCA-salt hypertension by modulation of neuroendocrine-related PVN nuclei rather than inhibition of PVN sympathetic premotor neurons in the PVN and rostroventrolateral medulla.

Abstract MP06: Kinin B1 Receptor Mediates Orexin System Hyperactivity In Salt-sensitive Hypertension

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Rohan U Parekh ◽  
Abdel A Abdel-rahman ◽  
Srinivas Sriramula
Keyword(s):  
Radio Telemetry ◽  
Mrna Levels ◽  
Wild Type ◽  
Salt Treatment ◽  
Neurogenic Hypertension ◽  
B1 Receptor ◽  
Kinin B1 Receptor ◽  
Salt Sensitive Hypertension ◽  
The Brain

Hyperactivity of the orexin system contributes to several animal models of hypertension and enhances arginine vasopressin (AVP) release. We previously reported higher neuronal kinin B1 receptor (B1R) expression and brain AVP levels in hypertensive mice. However, the role of B1R and its interaction with orexin system in neurogenic hypertension have not been studied. In the present study, we tested the hypothesis that kinin B1R contributes to hypertension by upregulation of orexin-AVP signaling in the brain. Deoxycorticosterone acetate (DOCA)-salt treatment (1 mg/g body weight DOCA, 1% saline in drinking water, 3 weeks) of wild-type (WT) male mice produced a significant increase in mean arterial pressure (MAP; radio-telemetry) (138 ±3 mmHg, n=8, p<0.01) that was blunted in B1R knockout mice (121±2 mmHg, P <0.05 vs. WT+DOCA). In WT mice, DOCA-salt, compared to vehicle, increased mRNA levels of orexin receptor 1 (2.5 fold, n=9, p<0.001), orexin receptor 2 (3 fold, n=9, p<0.001) and AVP (3 fold, n=9, p<0.01) in the hypothalamic paraventricular nucleus (PVN), and these DOCA-salt evoked effects were attenuated in B1RKO mice. Similarly, DOCA-salt evoked increases in protein expression of orexin receptor 1 and 2 in the hypothalamic PVN of WT mice were attenuated by 25±5% and 33±5% (p<0.05), respectively, in B1RKO vs WT+DOCA mice. Furthermore, DOCA-salt treatment increased plasma AVP levels in WT mice compared to vehicle treated mice (13.69±1.1 vs. 47.86±8.7 pg/ml, p<0.05), but not in B1RKO mice. Together, these data provide novel evidence that kinin B1R plays an important role in mediating DOCA-salt induced hypertension possibly via upregulating the orexin-AVP signaling in the brain.

Role of spinal neurons in the maintenance of elevated sympathetic activity: a novel therapeutic target?

2020 ◽  
Vol 319 (3) ◽  
pp. R282-R287
Author(s):  
Maycon I. O. Milanez ◽  
Erika E. Nishi ◽  
Cássia T. Bergamaschi ◽  
Ruy R. Campos
Keyword(s):  
Cardiovascular Diseases ◽  
Therapeutic Target ◽  
Sympathetic Activity ◽  
Spinal Neurons ◽  
Potential Therapeutic Target ◽  
Present Evidence ◽  
Extensive Range ◽  
Vasomotor Activity ◽  
The Brain

The control of sympathetic vasomotor activity involves a complex network within the brain and spinal circuits. An extensive range of studies has indicated that sympathoexcitation is a common feature in several cardiovascular diseases and that strategies to reduce sympathetic vasomotor overactivity in such conditions can be beneficial. In the present mini-review, we present evidence supporting the spinal cord as a potential therapeutic target to mitigate sympathetic vasomotor overactivity in cardiovascular diseases, focusing mainly on the actions of spinal angiotensin II on the control of sympathetic preganglionic neuronal activity.

Mesenteric vascular responses to vasopressin during development of DOCA-salt hypertension in male and female rats

1995 ◽  
Vol 268 (1) ◽  
pp. R40-R49 ◽  
Author(s):  
J. N. Stallone
Keyword(s):  
Sex Differences ◽  
Acute Treatment ◽  
Vascular Reactivity ◽  
Chronic Treatment ◽  
Female Rats ◽  
Salt Treatment ◽  
Male And Female Rats ◽  
Salt Hypertension ◽  
Vascular Responsiveness

Deoxycorticosterone acetate (DOCA)-salt hypertension develops to a greater extent in male (M) than in female (F) rats. To determine the role of the vasculature, reactivity to arginine vasopressin (AVP) and prostanoid output were examined in the isolated perfused mesenteric vasculature of hypertensive (HT) and normotensive-control (NTC) M and F rats after acute (1-wk) and chronic (4-wk) DOCA-salt treatment. Systolic blood pressure was significantly higher in M than in F HT rats (187 +/- 3 vs. 151 +/- 3 mmHg after 4 wk; P < 0.02). After acute treatment, vascular reactivity to AVP (maximal perfusion pressure) in HT was elevated in M (181 +/- 18 mmHg; P < 0.02) but not in F (135 +/- 6 mmHg) compared with NTC (90 +/- 6 mmHg, M vs. 119 +/- 5 mmHg, F). After chronic treatment, vascular reactivity to AVP in HT was elevated in both sexes (P < 0.02), although more in F (175 +/- 13 mmHg) than in M (141 +/- 11 mmHg). In contrast, vascular responsiveness to phenylephrine did not differ significantly between M and F NTC or HT preparations after either acute or chronic treatment. Sex differences in basal and AVP-induced 6-ketoprostaglandin (6-keto-PG) F1 alpha and PGE2 output by HT and NTC vasculature were reciprocal to sex differences in the vasoconstriction responses to AVP. After acute treatment, AVP-stimulated 6-keto-PGF1 alpha output by HT was elevated slightly in F (33.6 +/- 1.7 ng/3 min; P < or = 0.02) but not in M (49.9 +/- 4.3 ng/3 min) compared with NTC (23.5 +/- 2.6 ng/3 min, F vs. 34.7 +/- 4.9 ng/3 min, M). After chronic treatment, output by HT was enhanced in both sexes (P < or = to 0.02), although more in M (109 +/- 15.4 ng/3 min) than in F (68 +/- 6.6 ng/3 min)> These findings suggest that sex differences in the relative balance between AVP-induced vasoconstriction and vasodilatory prostanoid release may contribute to male-female differences in mesenteric vascular reactivity to AVP in NT and that disturbances in this balance may be responsible, at least in part, for the sex- and time-dependent changes in reactivity to AVP observed during the development of DOCA-salt hypertension.

Changes in renal and central noradrenergic activity with potassium in DOCA-salt rats

1984 ◽  
Vol 246 (5) ◽  
pp. F670-F675 ◽  
Author(s):  
T. Fujita ◽  
Y. Sato
Keyword(s):  
Urinary Sodium Excretion ◽  
Turnover Time ◽  
Hypertensive Rats ◽  
Potassium Supplement ◽  
Norepinephrine Concentration ◽  
Norepinephrine Turnover ◽  
Salt Hypertension ◽  
Rate Of Decline ◽  
The Brain

We studied the role of the renal and central noradrenergic neurons in the antihypertensive actions of potassium in DOCA-salt hypertensive rats. Supplementation with 0.2% KCl could moderate the development of the DOCA-salt hypertension. The potassium supplement attenuated sodium retention in the DOCA-salt rats, and, thus, sodium "space" at wk 4 was significantly smaller in the KCl-supplemented DOCA-salt rats than in the DOCA-salt rats. Norepinephrine turnover was measured from the rate of decline of tissue norepinephrine concentration after administration of alpha-methyl-p-tyrosine. Renal norepinephrine turnover was markedly accelerated in the DOCA-salt rats compared with the vehicle-treated control rats, but the 0.2% KCl supplements could normalize it. In contrast, turnover time in the hypothalamus and pons medulla was delayed in the DOCA-salt rats compared with the control rats, whereas 0.2% KCl supplements increased the norepinephrine turnover in the brain stem. These results suggest that the potassium-induced hypotensive actions in DOCA-salt rats may be attributed mainly to the augmented urinary sodium excretion. Moreover, it appears that the normalization of the increased renal sympathetic activity, which is intimately related to the central sympathoinhibitory noradrenergic mechanisms, may be involved in the natriuretic and antihypertensive actions of potassium in DOCA-salt hypertensive rats.

scholarly journals Disruption of CXCR6 Ameliorates Kidney Inflammation and Fibrosis in Deoxycorticosterone Acetate/Salt Hypertension

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yuanbo Wu ◽  
Changlong An ◽  
Xiaogao Jin ◽  
Zhaoyong Hu ◽  
Yanlin Wang
Keyword(s):  
Knockout Mice ◽  
Critical Role ◽  
Kidney Injury ◽  
Wild Type ◽  
Salt Treatment ◽  
Hypertensive Nephropathy ◽  
Deoxycorticosterone Acetate ◽  
Kidney Fibrosis ◽  
Salt Hypertension

AbstractCirculating cells have a pathogenic role in the development of hypertensive nephropathy. However, how these cells infiltrate into the kidney are not fully elucidated. In this study, we investigated the role of CXCR6 in deoxycorticosterone acetate (DOCA)/salt-induced inflammation and fibrosis of the kidney. Following uninephrectomy, wild-type and CXCR6 knockout mice were treated with DOCA/salt for 3 weeks. Blood pressure was similar between wild-type and CXCR6 knockout mice at baseline and after treatment with DOCA/salt. Wild-type mice develop significant kidney injury, proteinuria, and kidney fibrosis after three weeks of DOCA/salt treatment. CXCR6 deficiency ameliorated kidney injury, proteinuria, and kidney fibrosis following treatment with DOCA/salt. Moreover, CXCR6 deficiency inhibited accumulation of bone marrow–derived fibroblasts and myofibroblasts in the kidney following treatment with DOCA/salt. Furthermore, CXCR6 deficiency markedly reduced the number of macrophages and T cells in the kidney after DOCA/salt treatment. In summary, our results identify a critical role of CXCR6 in the development of inflammation and fibrosis of the kidney in salt-sensitive hypertension.

Regional Distribution of Angiotensinogen in the Central Nervous System of the Rat: Effect of DOC-Salt Treatment

1982 ◽  
Vol 63 (s8) ◽  
pp. 149s-152s ◽  
Author(s):  
Nidia Basso ◽  
Diana Grispon ◽  
Patricia Ruiz ◽  
Alberto C. Taquini
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Regional Distribution ◽  
Salt Treatment ◽  
Blood Contamination ◽  
Renin Substrate ◽  
Salt Hypertension ◽  
The Central Nervous System ◽  
The Brain

1. The distribution of angiotensinogen and endogenous renin-like activity were analysed in different areas of the central nervous system in normal and DOC-salt-treated hypertensive rats. 2. Angiotensinogen concentration and renin-like activity were significantly increased in the cerebral cortex, cerebellum, hypothalamus and brain stem of the DOC-salt-treated rats 30 days after the initiation of the experiment. 3. Influence of plasma contamination on the former results was evaluated by the determination of (a) plasma angiotensinogen concentration in control and treated animals and (b) blood content remaining in the different regions of the central nervous system, after saline perfusion of the brain, in a group of normal rats. 4. Plasma angiotensinogen concentration was significantly decreased in DOC-salt-treated rats, therefore blood contamination would tend to diminish the magnitude of increase in central nervous system angiotensinogen in these animals. 5. Present results have shown an increased concentration of angiotensinogen in some areas of the central nervous system in DOC-salt-treated rats. The results have also confirmed an enhanced activity of the endogenous renin-like enzyme in the same regions; this change seems to be mainly due to the increment in angiotensinogen. Increased formation of central angiotensin could be involved in the development of DOC-salt hypertension. The biosynthetic pathways of renin substrate as well as its endogenous regulation remain undetermined.

scholarly journals COX-2-independent activation of renal (pro)renin receptor contributes to DOCA-salt hypertension in rats

2020 ◽  
Vol 319 (4) ◽  
pp. F647-F653
Author(s):  
Fei Wang ◽  
Ying Sun ◽  
Renfei Luo ◽  
Xiaohan Lu ◽  
Baoxue Yang ◽  
...  
Keyword(s):  
Renal Medulla ◽  
Immunoblot Analysis ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Salt Treatment ◽  
Sprague Dawley Rats ◽  
Salt Hypertension ◽  
Cox 2 ◽  
Universal Mechanism

It has been shown that cyclooxygenase (COX)-2-dependent activation of renal (pro)renin receptor (PRR) contributes to angiotensin II (ANG II)-induced hypertension. However, less is known about the involvement of this mechanism in ANG II-independent hypertension. The goal of the present study was to test whether or not COX-2-dependent upregulation of PRR serves as a universal mechanism contributing to ANG II-dependent and -independent hypertension. Here, we examined the association between renal COX-2 and PRR during deoxycorticosterone acetate (DOCA)-salt hypertension in rats. By immunoblot analysis and immunofluorescence, renal protein expression of PRR was remarkably upregulated by DOCA-salt treatment. Surprisingly, this upregulation of renal PRR expression was unaffected by a COX-2 inhibitor, celecoxib. To address the role of renal PRR to the pathogenesis of DOCA-salt hypertension, a decoy PRR inhibitor, PRO20, was infused to the renal medulla of uninephrectomized Sprague-Dawley rats for 14 days. Radiotelemetry demonstrated effective attenuation of DOCA-salt hypertension by intramedullary infusion of a PRR inhibitor, PRO20. In parallel, DOCA-salt-induced hypertrophy in the heart and kidney as well as proteinuria were improved, accompanied with blunted polydipsia and polyuria. In contrast, intravenous infusion of PRO20 was less effective in attenuating DOCA-salt hypertension and cardiorenal injury. Together, these results suggest that COX-2-independent activation of renal PRR contributes to DOCA-salt hypertension.

Role of central mineralocorticoid binding sites in development of hypertension

1990 ◽  
Vol 259 (5) ◽  
pp. R1025-R1034 ◽  
Author(s):  
P. C. Janiak ◽  
S. J. Lewis ◽  
M. J. Brody
Keyword(s):  
Binding Sites ◽  
Renal Hypertension ◽  
Vasomotor Tone ◽  
Salt Treatment ◽  
Mineralocorticoid Receptor Antagonist ◽  
Antihypertensive Action ◽  
Mineralocorticoid Antagonist ◽  
Salt Hypertension ◽  
Ru 28318

The possibility that central mineralocorticoid binding sites are involved in the development of mineralocorticoid hypertension was examined using chronic blockade of these sites with a specific mineralocorticoid receptor antagonist RU 28318 administered by intracerebroventricular (icv) infusion. The antagonist significantly attenuated the development of deoxycorticosterone acetate (DOCA)-salt hypertension, but the development of one-kidney, one-clip renal hypertension was not affected. This antihypertensive action was attributable to a central action, since intraperitoneal infusion of the same dose of mineralocorticoid antagonist did not alter the peak development of DOCA-salt hypertension. The icv infusion of RU 28318 did not change either the increase of fluid intake induced by DOCA-salt treatment or the pressor reactivity to centrally or peripherally injected arginine vasopressin and angiotensin II and peripherally administered phenylephrine. The antihypertensive action of icv infusion of the mineralocorticoid antagonist was associated with a reduction of neurogenic vasomotor tone and a restoration of impaired arterial baroreflexes. We conclude that functional integrity of central mineralocorticoid binding sites is required for the full development of DOCA-salt hypertension.

scholarly journals Splanchnic sympathetic nerves in the development of mild DOCA-salt hypertension

2011 ◽  
Vol 301 (5) ◽  
pp. H1965-H1973 ◽  
Author(s):  
Sachin S. Kandlikar ◽  
Gregory D. Fink
Keyword(s):  
Vascular Reactivity ◽  
Sympathetic Nerves ◽  
Whole Body ◽  
Renal Nerves ◽  
Salt Treatment ◽  
Salt Hypertension ◽  
Celiac Ganglionectomy ◽  
Hypertension Development ◽  
Final Group

We previously reported that mild deoxycorticosterone acetate (DOCA)-salt hypertension develops in the absence of generalized sympathoexcitation. However, sympathetic nervous system activity (SNA) is regionally heterogeneous, so we began to investigate the role of sympathetic nerves to specific regions. Our first study on that possibility revealed no contribution of renal nerves to hypertension development. The splanchnic sympathetic nerves are implicated in blood pressure (BP) regulation because splanchnic denervation effectively lowers BP in human hypertension. Here we tested the hypothesis that splanchnic SNA contributes to the development of mild DOCA-salt hypertension. Splanchnic denervation was achieved by celiac ganglionectomy (CGX) in one group of rats while another group underwent sham surgery (SHAM-GX). After DOCA treatment (50 mg/kg) in rats with both kidneys intact, CGX rats exhibited a significantly attenuated increase in BP compared with SHAM-GX rats (15.6 ± 2.2 vs. 25.6 ± 2.2 mmHg, day 28 after DOCA treatment). In other rats, whole body norepinephrine (NE) spillover, measured to determine if CGX attenuated hypertension development by reducing global SNA, was not found to be different between SHAM-GX and CGX rats. In a third group, nonhepatic splanchnic NE spillover was measured as an index of splanchnic SNA, but this was not different between SHAM (non-DOCA-treated) and DOCA rats during hypertension development. In a final group, CGX effectively abolished nonhepatic splanchnic NE spillover. These data suggest that an intact splanchnic innervation is necessary for mild DOCA-salt hypertension development but not increased splanchnic SNA or NE release. Increased splanchnic vascular reactivity to NE during DOCA-salt treatment is one possible explanation.

scholarly journals Awake reactivation and suppression after brief task exposure depend on task novelty

2019 ◽  
Author(s):  
Ji Won Bang ◽  
Dobromir Rahnev
Keyword(s):  
Performance Improvement ◽  
Neural Activity ◽  
Memory Consolidation ◽  
The Novel ◽  
Exact Role ◽  
Visual Training ◽  
Early Visual Cortex ◽  
Task Processing ◽  
The Brain

AbstractPreviously learned information is known to be reactivated during periods of quiet wakefulness and such awake reactivation is considered to be a key mechanism for memory consolidation. We recently demonstrated that feature-specific awake reactivation occurs in early visual cortex immediately after extensive visual training on a novel task. To understand the exact role of awake reactivation, here we investigated whether such reactivation depends specifically on the task novelty. Subjects completed a brief visual task that was either novel or extensively trained on previous days. Replicating our previous results, we found that awake reactivation occurs for the novel task even after a brief learning period. Surprisingly, however, brief exposure to the extensively trained task led to “awake suppression” such that neural activity immediately after the exposure diverged from the pattern for the trained task. Further, subjects who had greater performance improvement showed stronger awake suppression. These results suggest that the brain operates different post-task processing depending on prior visual training.

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