Dependence of Deoxycorticosterone/Salt Hypertension in the Rat on the Activity of Adrenergic Cardiac Nerves

1979 ◽  
Vol 57 (2) ◽  
pp. 203-210 ◽  
Author(s):  
C. Bell ◽  
Elspeth M. McLachlan
Keyword(s):  
Wistar Rats ◽  
Chronic Hypertension ◽  
Subcutaneous Implantation ◽  
Salt Treatment ◽  
Sodium Load ◽  
Salt Hypertension ◽  
Neonatal Administration ◽  
Tail Cuff ◽  
Inactivation Of Noradrenaline ◽  
Cardiac Nerves

1. Chronic hypertension was induced in Wistar rats with intact kidneys by subcutaneous implantation of 50 mg of deoxycorticosterone acetate (DOC A) in wax and addition of sodium chloride (9 g/l) to the drinking water. 2. The development of DOCA/salt hypertension, as monitored by tail-cuff plethysmography, was prevented by: (a) destruction of the peripheral adrenergic nerves with neonatal administration of guanethidine (80 mg/kg subcutaneously for the first 14 days postnatally); (b) bilateral stellate ganglionectomy; (c) oral administration of the β-adrenoreceptor antagonists propranolol or atenolol (1 mg day−1 kg−1) during the period of DOCA/salt treatment. 3. The dose of DOCA used was sufficient to inhibit the atrial Uptake2 pathway completely: this process appears to participate in termination of action of neurally released noradrenaline in the heart. 4. It is suggested that this model of DOCA/salt hypertension is due to adrenergic enhancement of cardiac output in the presence of an increased sodium load. The enhancement may be partly due to deficient myocardial inactivation of noradrenaline.

Endothelium, vasopressin receptors, and resistance to DOCA-salt hypertension

1993 ◽  
Vol 265 (1) ◽  
pp. H15-H21 ◽  
Author(s):  
C. S. Bockman ◽  
W. B. Jeffries ◽  
W. A. Pettinger ◽  
P. W. Abel
Keyword(s):  
Mesenteric Artery ◽  
Wistar Rats ◽  
Fold Increase ◽  
Vasopressin Receptor ◽  
Receptor Function ◽  
Salt Treatment ◽  
Threefold Increase ◽  
Lysine Vasopressin ◽  
Salt Hypertension ◽  
Vasopressin Receptors

Mesenteric artery rings from Wistar and Wistar-Furth rats subcutaneously treated with deoxycorticosterone acetate (DOCA) and 1% NaCl drinking water were used to measure endothelial modulation of contractile sensitivity and vasopressin receptor function and affinity. DOCA-salt hypertension reduced contractile sensitivity to arginine vasopressin (AVP) and did not affect contractile sensitivity to norepinephrine in arteries from Wistar rats. Endothelial removal caused a threefold increase in contractile sensitivity to AVP and norepinephrine in DOCA-salt hypertensive Wistar rats. In Wistar-Furth rats, DOCA-salt treatment did not affect contractile sensitivity to AVP, lysine vasopressin, oxytocin, and norepinephrine or the affinity of the vasopressin receptor for agonists or antagonists. Removal of endothelium did not affect vasopressin contractile sensitivity but caused a 15-fold increase in contractile sensitivity to norepinephrine in untreated or DOCA-salt-treated Wistar-Furth rats. These data show that reduced vasopressin receptor function and increased endothelial function that compensate for increased contractile sensitivity in arteries from DOCA-salt hypertensive Wistar rats are not the cause of resistance of DOCA-salt-treated Wistar-Furth rats to the development of enhanced contractile sensitivity and hypertension.

Control of spontaneous and deoxycorticosterone–salt hypertension and polyuria by nitrendipine pellets

1984 ◽  
Vol 62 (4) ◽  
pp. 436-440 ◽  
Author(s):  
Charles E. Hall ◽  
Shirley Hungerford
Keyword(s):  
Cardiac Hypertrophy ◽  
Diabetes Insipidus ◽  
Spontaneously Hypertensive Rats ◽  
Potassium Excretion ◽  
Subcutaneous Implantation ◽  
Hypertensive Rats ◽  
Salt Treatment ◽  
Spontaneously Hypertensive ◽  
Salt Hypertension ◽  
Blood Pressures

Weekly subcutaneous implantation of 25-mg nitrendipine pellets prevented onset of both spontaneous and deoxycorticosterone–salt hypertension in rats. Discontinuance of implantation led to reappearance of hypertension after about 2 weeks in the former and led to rising though still normotensive pressures after about 3 weeks in the latter. A new implant caused blood pressures in both to drop within a day or two to normotensive levels in the case of spontaneously hypertensive rats. Nitrendipine prevented cardiac hypertrophy in steroid hypertensive rats, but not in spontaneous hypertensives. A nitrendipine pellet given 1 day before or a 30 mg/kg injection given 1 h prior to the administration of a water, Na+, and K+ load, prevented the diabetes insipidus-like syndrome resulting from deoxycorticosterone–salt treatment, and lowered sodium but not potassium excretion. Nitrendipine did not affect steroid-induced hypernatremia and hypokalemia.

Abstract 103: ACE2 Overexpression Prevents DOCA-Salt Hypertension by Modulating Oxidative Stress and Nitric Oxide in the Central Nervous System

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Srinivas Sriramula ◽  
Huijing Xia ◽  
Eric Lazartigues
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Central Nervous System ◽  
Nervous System ◽  
Nadph Oxidase ◽  
Salt Treatment ◽  
Salt Hypertension ◽  
The Central Nervous System ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Elevated reactive oxygen species (ROS) in the central nervous system (CNS) through NADPH oxidase and diminished Nitric oxide (NO) levels are involved in the pathogenesis of hypertension. We previously reported that central Angiotensin Converting Enzyme 2 (ACE2) overexpression prevents the development of hypertension induced by DOCA-salt in a transgenic mouse model (syn-hACE2; SA) with human ACE2 targeted selectively to neurons in the CNS. While baseline blood pressure (BP; telemetry) was not different among genotypes, DOCA-salt treatment (1mg/g body wt DOCA, 1% saline in drinking water for 3 weeks) resulted in significantly lower BP level in SA mice (122 ±3 mmHg, n=12) compared to non-transgenic (NT) littermates (138 ±3 mmHg, n=8). To elucidate the mechanisms involved in this response, we investigated the paraventricular nucleus (PVN) expression of Nox-2 (catalytic subunit of NADPH oxidase), 3-nitrotyrosine, and endothelial nitric oxide synthase (eNOS) and anti-oxidant enzymes superoxide dismutase (SOD) and catalase in the hypothalamus. DOCA-salt treatment resulted in decreased catalase (95.2 ±5.6 vs. 113.8 ±17.6 mmol/min/ml, p<0.05) and SOD (4.1 ±0.4 vs. 5.9 ±0.2 U/ml, p<0.01) activities in hypothalamic homogenates of NT mice, which was prevented by ACE2 overexpression (141.8 ±9.9 vs. 142.1 ±9.2 mmol/min/ml and 5.9 ±0.3 vs. 7.9 ±0.2 U/ml, respectively). NT mice treated with DOCA-salt showed increased oxidative stress as indicated by increased expression of Nox-2 (61 ±5 % increase, n=9, p<0.001 vs. NT) and 3-nitrotyrosine (89 ±32 % increase, n=9, p<0.01 vs. NT) in the PVN which was attenuated in SA mice. Furthermore, DOCA-salt hypertension resulted in decreased phosphorylation of eNOS-ser1177 in the PVN (33 ±5 % decrease, n=9, p<0.05 vs NT) and this decrease was prevented by ACE2 overexpression. Taken together, these data provide evidence that brain ACE2 regulates the balance between NO and ROS levels, thereby preventing the development of DOCA-salt hypertension.

scholarly journals Aggravated renal inflammatory responses in TRPV1 gene knockout mice subjected to DOCA-salt hypertension

2009 ◽  
Vol 297 (6) ◽  
pp. F1550-F1559 ◽  
Author(s):  
Youping Wang ◽  
Donna H. Wang
Keyword(s):  
Transient Receptor Potential ◽  
Inflammatory Responses ◽  
Gene Knockout ◽  
Periodic Acid ◽  
Immunosuppressive Drug ◽  
Transient Receptor Potential Vanilloid ◽  
Tubulointerstitial Injury ◽  
Salt Treatment ◽  
Periodic Acid Schiff ◽  
Salt Hypertension

To test the hypothesis that deletion of the transient receptor potential vanilloid type 1 (TRPV1) channel exaggerates hypertension-induced renal inflammatory response, wild-type (WT) or TRPV1-null mutant (TRPV1−/−) mice were subjected to uninephrectomy and deoxycorticosterone acetate (DOCA)-salt treatment for 4 wk. Mean arterial pressure (MAP) determined by radiotelemetry increased in DOCA-salt-treated WT or TRPV1−/− mice, whereas there was no difference in MAP between two strains at the baseline or after DOCA-salt treatment. DOCA-salt treatment increased urinary excretion of albumin and 8-isoprostane in both WT and TRPV1−/− mice, and the increases were greater in magnitude in the latter strain. Periodic acid-Schiff and Mason's trichrome staining showed that kidneys of DOCA-salt-treated TRPV1−/− mice exhibited more severe glomerulosclerosis and tubulointerstitial injury compared with DOCA-salt-treated WT mice. NF-κB assay showed that DOCA-salt treatment increased renal activated NF-κB concentrations in TRPV1−/− mice compared with WT mice. Immunostaining and ELISA assay revealed that DOCA-salt-treated TRPV1−/− mice had enhanced renal infiltration of monocyte/macrophage and lymphocyte, as well as increased renal levels of proinflammatory cytokine (TNF-α, IL-6) and chemokine (MCP-1) compared with DOCA-salt-treated WT mice. Renal ICAM-1 but not VCAM-1 expression was also greater in DOCA-salt-treated TRPV1−/− than WT mice. Dexamethasone (DEXA), an immunosuppressive drug, conveyed a renoprotective effect that was greater in DOCA-salt-treated TRPV1−/− compared with WT mice. These data show that renal inflammation is exacerbated in DOCA-salt hypertension when TRPV1 gene is deleted and that the deterioration is ameliorated by DEXA treatment, indicating that TRPV1 may act as a potential regulator of the inflammatory process to lessen renal injury in DOCA-salt hypertension.

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.

scholarly journals Role of Substance P in Renal Injury During DOCA-Salt Hypertension

Endocrinology ◽  
2012 ◽  
Vol 153 (12) ◽  
pp. 5972-5979 ◽  
Author(s):  
Youping Wang ◽  
Donna H. Wang
Keyword(s):  
Substance P ◽  
Renal Injury ◽  
Tissue Injury ◽  
Periodic Acid ◽  
Sensory Nerves ◽  
Macrophage Infiltration ◽  
Tubulointerstitial Injury ◽  
Salt Treatment ◽  
Albumin Excretion ◽  
Salt Hypertension

Abstract Substance P (SP), a neurokinin-1 receptor (NK-1R) agonist, is mainly produced and stored in primary sensory nerves and, upon its release, participates in cardiovascular and renal functional regulation. This study tests the hypothesis that activation of the NK-1Rs by SP occurs during hypertension induced by deoxycorticosterone (DOCA)-salt treatment, which contributes to renal injury in this model. C57BL/6 mice were subjected to uninephrectomy and DOCA-salt treatment in the presence or absence of administration of selective NK-1 antagonists, L-733,060 (20 mg/kg·d, ip) or RP-67580 (8 mg/kg·d, ip). Five weeks after the treatment, mean arterial pressure determined by the telemetry system increased in DOCA-salt mice but without difference between NK-1R antagonist-treated or NK-1R antagonist-untreated DOCA-salt groups. Plasma SP levels were increased in DOCA-salt compared with control mice (P &lt; 0.05). Renal hypertrophy and increased urinary 8-isoprostane and albumin excretion were observed in DOCA-salt compared with control mice (P &lt; 0.05). Periodic acid-Schiff and Masson's trichrome staining showed more severe glomerulosclerosis and tubulointerstitial injury in the renal cortex in DOCA-salt compared with control mice, respectively (P &lt; 0.05). Hydroxyproline assay and F4/80-staining showed that renal collagen levels and interstitial monocyte/macrophage infiltration were greater in DOCA-salt compared with control mice, respectively (P &lt; 0.05). Blockade of the NK-1R with L-733,060 or RP-67580 in DOCA-salt mice suppressed increments in urinary 8-isoprostane and albumin excretion, interstitial monocyte/macrophage infiltration, and glomerulosclerosis and tubulointerstitial injury and fibrosis (P &lt; 0.05). Thus, our data show that blockade of the NK-1Rs alleviates renal functional and tissue injury in the absence of alteration in blood pressure in DOCA-salt-hypertensive mice. The results suggest that elevated SP levels during DOCA-salt hypertension play a significant role contributing to renal damage possibly via enhancing oxidative stress and macrophage infiltration of the kidney.

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.

Defective renal dopamine function and sodium-sensitive hypertension in adult ovariectomized Wistar rats: role of the cytochromeP-450 pathway

2015 ◽  
Vol 308 (12) ◽  
pp. F1358-F1368 ◽  
Author(s):  
Luis A. Di Ciano ◽  
Pablo J. Azurmendi ◽  
Cecilia Colombero ◽  
Gloria Levin ◽  
Elisabet M. Oddo ◽  
...  
Keyword(s):  
Sodium Excretion ◽  
Wistar Rats ◽  
Sch 23390 ◽  
D1 Receptor ◽  
Phosphorylation State ◽  
High Sodium ◽  
Ovx Rats ◽  
Sodium Load ◽  
Renal Dopamine ◽  
Salt Sensitive Hypertension

We have previously shown that ovariectomy in adult Wistar rats under normal sodium (NS) intake results in an overexpression of the total Na+-K+-ATPase (NKA) α1-subunit (Di Ciano LA, Azurmendi PJ, Toledo JE, Oddo EM, Zotta E, Ochoa F, Arrizurieta EE, Ibarra FR. Clin Exp Hypertens 35: 475–483, 2013). Upon high sodium (HS) intake, ovariectomized (oVx) rats developed defective NKA phosphorylation, a decrease in sodium excretion, and an increment in mean blood pressure (MBP). Since NKA phosphorylation is modulated by dopamine (DA), the aim of this study was to compare the intracellular response of the renal DA system leading to NKA phosphorylation upon sodium challenge in intact female (IF) and oVx rats. In IF rats, HS caused an increase in urinary DA and sodium, in NKA phosphorylation state, in cytochrome P-4504A (CYP4A) expression, and in 20-HETE production, while MBP kept normal. Blockade of the D1 receptor (D1R) with the D1-like receptor antagonist SCH 23390 in IFHS rats shifted NKA into a more dephosphorylated state, decreased sodium excretion by 50%, and increased MBP. In oVxNS rats, D1R expression was reduced and D3R expression was increased, and under HS intake sodium excretion was lower and MBP higher than in IFHS rats (both P < 0.05), NKA was more dephosphorylated than in IFHS, and CYP4A expression or 20-HETE production did not change. Blockade of D1R in oVxHS rats changed neither NKA phosphorylation state nor sodium excretion or MBP. D2R and PKCα expression did not vary among groups. The alteration of the renal DA system produced by ovariectomy could account for the defective NKA phosphorylation, the inefficient excretion of sodium load, and the development of 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.

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