Effect of central amiloride infusion on mineralocorticoid hypertension

1994 ◽  
Vol 267 (5) ◽  
pp. E754-E758 ◽  
Author(s):  
E. P. Gomez-Sanchez ◽  
C. E. Gomez-Sanchez
Keyword(s):  
Blood Pressure ◽  
Urine Volume ◽  
Na Channel ◽  
Sprague Dawley ◽  
Cellular Mechanisms ◽  
Subcutaneous Infusion ◽  
Intracerebroventricular Infusion ◽  
Sprague Dawley Rats ◽  
Different Types ◽  
The Brain

There is strong evidence from different types of studies, including the discrete infusion of agonists and antagonists and ablation of specific brain areas or transmitter-type neurons, that mineralocorticoids, in excess, act in the brain to elevate blood pressure. Aldosterone enhances the entry of Na+ through amiloride-sensitive Na+ channels in some mineralocorticoid-sensitive transport epithelial cells. To define possible cellular mechanisms involved in central mineralocorticoid action, benzamil, an amiloride analogue with selective affinity for the Na+ channel, was continuously infused intracerebroventricularly in three mineralocorticoid-dependent hypertension models in Sprague-Dawley rats, the continuous subcutaneous infusion of aldosterone, the intracerebroventricular infusion of aldosterone, and the ingestion of carbenoxolone, a synthetic licorice analogue. The intracerebroventricular infusion of 0.3 and 0.5 micrograms/h of benzamil, doses that did not have an adverse effect on growth and that had no effect on the blood pressure when infused subcutaneously, prevented the increase in blood pressure in these models. The infusion of these levels of benzamil had no effect on urine volume even in those animals in which it prevented an increase in blood pressure. These data suggest that the central effects of mineralocorticoids on blood pressure are mediated, at least in part, by the effects of mineralocorticoids on amiloride-sensitive sodium transport.

Abstract 114: K+ Rich Diet During Angiotensin II Hypertension Reduces Renal Na-Cl Cotransporter and Phosphorylation, but Not Blood Pressure

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Luciana C Veiras ◽  
Jiyang Han ◽  
Donna L Ralph ◽  
Alicia A McDonough
Keyword(s):  
Blood Pressure ◽  
Urine Volume ◽  
Weight Ratio ◽  
Distal Tubule ◽  
Reduce Blood Pressure ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
K Secretion ◽  
Pressure Natriuresis

During Ang II hypertension distal tubule Na-Cl Cotransporter (NCC) abundance and its activating phosphorylation (NCCp), as well as Epithelial Na+ channels (ENaC) abundance and activating cleavage are increased 1.5-3 fold. Fasting plasma [K+] is significantly lower in Ang II hypertension (3.3 ± 0.1 mM) versus controls (4.0 ± 0.1 mM), likely secondary to ENaC stimulation driving K+ secretion. The aim of this study was to test the hypothesis that doubling dietary K+ intake during Ang II infusion will lower NCC and NCCp abundance to increase Na+ delivery to ENaC to drive K+ excretion and reduce blood pressure. Methods: Male Sprague Dawley rats (225-250 g; n= 7-9/group) were treated over 2 weeks: 1) Control 1% K diet fed (C1K); 2) Ang II infused (400 ng/kg/min) 1% K diet fed (A1K); or 3) Ang II infused 2% K diet fed (A2K). Blood pressure (BP) was determined by tail cuff, electrolytes by flame photometry and transporters’ abundance by immunoblot of cortical homogenates. Results: As previously reported, Ang II infusion increased systolic BP (from 132 ± 5 to 197 ± 4 mmHg), urine volume (UV, 2.4 fold), urine Na+ (UNaV, 1.3 fold), heart /body weight ratio (1.23 fold) and clearance of endogenous Li+ (CLi, measures fluid volume leaving the proximal tubule, from 0.26 ± 0.02 to 0.51 ± 0.01 ml/min/kg) all evidence for pressure natriuresis. A2K rats exhibited normal plasma [K+] (4.6 ± 0.1 mM, unfasted), doubled urine K+ (UKV, from 0.20 to 0.44 mmol/hr), and increased CLi (to 0.8 ± 0.1 ml/min/kg) but UV, UNaV, cardiac hypertrophy and BP were unchanged versus the A1K group. As expected, NCC, NCCpS71 and NCCpT53 abundance increased in the A1K group to 1.5 ± 0.1, 2.9 ± 0.5 and 2.8 ± 0.4 fold versus C1K, respectively. As predicted by our hypothesis, when dietary K+ was doubled (A2K), Ang II infusion did not activate NCC, NCCpS71 nor NCCpT53 (0.91 ± 0.04, 1.3 ± 0.1 and 1.6 ± 0.2 fold versus C1K, respectively). ENaC subunit abundance and cleavage increased 1.5 to 3 fold in both A1K and A2K groups; ROMK was unaffected by Ang II or dietary K. In conclusion, evidence is presented that stimulation of NCC during Ang II hypertension is secondary to K+ deficiency driven by ENaC stimulation since doubling dietary K+ prevents the activation. The results also indicate that elevation in BP is independent of NCC activation

Increased renal α-ENaC and NCC abundance and elevated blood pressure are independent of hyperaldosteronism in vasopressin escape

2006 ◽  
Vol 291 (1) ◽  
pp. F49-F57 ◽  
Author(s):  
Swasti Tiwari ◽  
Randall K. Packer ◽  
Xinqun Hu ◽  
Yoshihisa Sugimura ◽  
Joseph G. Verbalis ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Urine Volume ◽  
Sprague Dawley ◽  
Α Subunit ◽  
Water Load ◽  
Arterial Blood ◽  
Sprague Dawley Rats ◽  
Solid Diet ◽  
Epithelial Sodium Channel Enac

Previously, we demonstrated that rats undergoing vasopressin escape had increased mean arterial blood pressure (MAP), plasma and urine aldosterone, and increased renal protein abundance of the α-subunit of the epithelial sodium channel (ENaC), the thiazide-sensitive Na-Cl cotransporter (NCC), and the 70-kDa band of γ-ENaC (Song J, Hu X, Khan O, Tian Y, Verbalis JG, and Ecelbarger CA. Am J Physiol Renal Physiol 287: F1076–F1083, 2004; Ecelbarger CA, Knepper MA, and Verbalis JG. J Am Soc Nephrol 12: 207–217, 2001). Here, we determine whether changes in these renal proteins and MAP require elevated aldosterone levels. We performed adrenalectomies (ADX) or sham surgeries on male Sprague-Dawley rats. Corticosterone and aldosterone were replaced to clamp these hormone levels. MAP was monitored by radiotelemetry. Rats were infused with 1-deamino-[8-d-arginine]-vasopressin (dDAVP) via osmotic minipumps (5 ng/h). At day 3 of dDAVP infusion, seven rats in each group were offered a liquid diet [water load (WL)] or continued on a solid diet (SD). Plasma aldosterone and corticosterone and urine aldosterone were increased by WL in sham rats. ADX-WL rats escaped, as assessed by early natriuresis followed by diuresis; however, urine volume and natriuresis were somewhat blunted. WL did not reduce the abundance or activity of 11-β-hydroxsteroid dehydrogenase type 2. Furthermore, the previously observed increase in renal aldosterone-sensitive proteins and escape-associated increased MAP persisted in clamped rats. The densitometry of immunoblots for NCC, α- and γ-70 kDa ENaC, respectively, were (% sham-SD): sham-WL, 159, 278, 233; ADX-SD, 69, 212, 171; ADX-WL, 116, 302, 161. However, clamping corticosteroids blunted the rise at least for NCC and γ-ENaC (70 kDa). Overall, the increase in aldosterone observed in vasopressin escape is not necessary for the increased expression of NCC, α- or γ-ENaC or increased MAP associated with “escape.”

scholarly journals Increased blood pressure, aldosterone activity, and regional differences in renal ENaC protein during vasopressin escape

2004 ◽  
Vol 287 (5) ◽  
pp. F1076-F1083 ◽  
Author(s):  
Jian Song ◽  
Xinqun Hu ◽  
Osman Khan ◽  
Ying Tian ◽  
Joseph G. Verbalis ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Regional Differences ◽  
Water Retention ◽  
Urine Volume ◽  
Hydroxysteroid Dehydrogenase ◽  
Plasma Aldosterone ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Sustained Increase

The syndrome of inappropriate antidiuretic hormone (SIADH) is associated with water retention and hyponatremia. The kidney adapts via a transient natriuresis and persistent diuresis, i.e., vasopressin escape. Previously, we showed an increase in the whole kidney abundance of aldosterone-sensitive proteins, the α- and γ (70-kDa-band)-subunits of the epithelial Na+ channel (ENaC), and the thiazide-sensitive Na-Cl cotransporter (NCC) in our rat model of SIADH. Here we examine mean arterial pressure via radiotelemetry, aldosterone activity, and cortical vs. medullary ENaC subunit and 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD-2) protein abundances in escape. Eighteen male Sprague-Dawley rats (300 g) were sham operated ( n = 6) or infused with desmopressin (dDAVP; n = 12, a V2 receptor-selective analog of AVP). After 4 days, one-half of the rats receiving dDAVP were switched to a liquid diet, i.e., water loaded (WL) for 5–7 additional days. The WL rats had a sustained increase in urine volume and blood pressure (122 vs. 104 mmHg, P < 0.03, at 7 days). Urine and plasma aldosterone levels were increased in the WL group to 844 and 1,658% of the dDAVP group, respectively. NCC and α- and γ-ENaC (70-kDa band) were increased significantly in the WL group (relative to dDAVP), only in the cortex. β- and γ-ENaC (85-kDa band) were increased significantly by dDAVP in cortex and medulla relative to control. 11β-HSD-2 was increased by dDAVP in the cortex and not significantly affected by water loading. These changes may serve to attenuate Na+ losses and ameliorate hyponatremia in vasopressin escape.

scholarly journals Sites and sources of sympathoexcitation in obese male rats: role of brain insulin

2020 ◽  
Vol 318 (3) ◽  
pp. R634-R648 ◽  
Author(s):  
Zhigang Shi ◽  
Ding Zhao ◽  
Priscila A. Cassaglia ◽  
Virginia L. Brooks
Keyword(s):  
Insulin Receptors ◽  
Male Rats ◽  
Melanocortin Receptor ◽  
Sprague Dawley ◽  
Intracerebroventricular Infusion ◽  
Sprague Dawley Rats ◽  
Y1 Receptors ◽  
The Brain ◽  
Obese Male

In males, obesity increases sympathetic nerve activity (SNA), but the mechanisms are unclear. Here, we investigate insulin, via an action in the arcuate nucleus (ArcN), and downstream neuropathways, including melanocortin receptor 3/4 (MC3/4R) in the hypothalamic paraventricular nucleus (PVN) and dorsal medial hypothalamus (DMH). We studied conscious and α-chloralose-anesthetized Sprague-Dawley rats fed a high-fat diet, which causes obesity prone (OP) rats to accrue excess fat and obesity-resistant (OR) rats to maintain fat content, similar to rats fed a standard control (CON) diet. Nonspecific blockade of the ArcN with muscimol and specific blockade of ArcN insulin receptors (InsR) decreased lumbar SNA (LSNA), heart rate (HR), and mean arterial pressure (MAP) in OP, but not OR or CON, rats, indicating that insulin supports LSNA in obese males. In conscious rats, intracerebroventricular infusion of insulin increased MAP only in OP rats and also improved HR baroreflex function from subnormal to supranormal. The brain sensitization to insulin may elucidate how insulin can drive central SNA pathways when transport of insulin across the blood-brain barrier may be impaired. Blockade of PVN, but not DMH, MC3/4R with SHU9119 decreased LSNA, HR, and, MAP in OP, but not OR or CON, rats. Interestingly, nanoinjection of the MC3/4R agonist melanotan II (MTII) into the PVN increased LSNA only in OP rats, similar to PVN MTII-induced increases in LSNA in CON rats after blockade of sympathoinhibitory neuropeptide Y Y1 receptors. ArcN InsR expression was not increased in OP rats. Collectively, these data indicate that obesity increases SNA, in part via increased InsR signaling and downstream PVN MC3/4R.

Effect of central infusion of benzamil on Dahl S rat hypertension

1995 ◽  
Vol 269 (3) ◽  
pp. H1044-H1047 ◽  
Author(s):  
E. P. Gomez-Sanchez ◽  
C. E. Gomez-Sanchez
Keyword(s):  
Blood Pressure ◽  
Drinking Water ◽  
Weight Gain ◽  
Na Channel ◽  
Subcutaneous Infusion ◽  
Intracerebroventricular Infusion ◽  
Significant Difference ◽  
Induced Hypertension ◽  
Blood Pressures

The effect of continuous central infusion of benzamil, a Na+ channel-selective amiloride analogue, on the salt-induced hypertension in inbred Dahl salt-sensitive (SS/jr) rats was assessed. The continuous intracerebroventricular or subcutaneous infusion of benzamil at doses which have no effect when infused systemically was started at the same time or 2 wk after saline was substituted for drinking water, when the rats' blood pressures had become significantly elevated. Within 13 days, drinking saline caused a similar and significant increase in the blood pressures of rats receiving the vehicle intracerebroventricularly and 1 microgram/h of benzamil subcutaneously, which persisted throughout the 4-wk experiment. The intracerebroventricular infusion of 1 or 0.3 microgram/h benzamil, started at the same time the salt challenge was instituted, significantly deterred the increase in blood pressure over 4 wk. The intracerebroventricular, but not the subcutaneous, infusion of benzamil at 0.5 microgram/h arrested the increase in blood pressure in rats that were already hypertensive after 12 days on saline. Within 3 days the pressures in the intracerebroventricular and subcutaneous benzamil groups became significantly different, due to the further increase of the blood pressure in those animals receiving the intracerebroventricular vehicle with subcutaneous benzamil. There was no significant difference in weight gain throughout the experiment or in 24-h urine volumes and urinary Na(+)-to-K+ ratio at days 5 and 12 of benzamil infusion between groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract P040: Pressure Natriuresis In Female Sprague Dawley Rats: Characteristics And Mechanisms

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Brandon E McFarlin ◽  
Donna L Ralph ◽  
Alicia A McDonough
Keyword(s):  
Blood Pressure ◽  
Mean Arterial Pressure ◽  
Carotid Artery ◽  
Urine Volume ◽  
Volume Flow ◽  
Lithium Clearance ◽  
Sprague Dawley ◽  
Electrolyte Excretion ◽  
Sprague Dawley Rats ◽  
Pressure Natriuresis

Raising blood pressure stimulates pressure natriuresis (P-Nat). In males (M) Sprague Dawley rats (SDR), Na + reabsorption (T Na ) is acutely reduced by retraction of proximal tubule (PT) NHE3 to microvillar base and NaPi2 internalization. In females (F), at baseline PT NHE3 is already at microvillar base and NaPi2 is less abundant than in M. We AIM to determine characteristics and mechanisms of P-Nat in F (vs M) rats. Methods: Inactin anesthetized F and M SDR (n=5/group) were provoked by vasoconstriction (or sham). Mean arterial pressure (MAP) was recorded via carotid artery, urine collected via bladder, Na + transporters’ abundance assessed via immunoblot and localization by immunohistochemistry. Results (Fig 1A): Baseline MAP (mmHg) was lower in F vs. M (91 ± 5 vs.105 ± 3, P =0.04) while urine volume (UV) and electrolyte excretion (UNaV, UKV) were similar. After celiac and mesenteric bed constriction, MAP rose to 128 ± 3 mmHg in both sexes; UNaV, UV and C Na increased 12 to 15-fold in F (all P <0.01) vs 6-fold in M ( P >0.08). Constriction of abdominal aorta further raised UNaV in F with less impact in M. Na + transporters . In F, NHE3 remained at PT microvillar base and NaPi2 was internalized with vasoconstriction. NHE3P (indicating inactivation) abundance increased 29% in F, P =0.058. Lithium clearance, measure of volume flow leaving early nephron, increased 9-fold in F ( P =0.02) vs. 5-fold in M ( P =0.07). F mTAL NHE3, NKCC2p, and SPAKp (co-transporter kinase) abundances were 22, 24, and 43% lower vs shams ( ANOVA P <0.0001). Summary: F vs M SDR exhibit more robust P-Nat associated with less T Na in early nephron and reductions in PT-mTAL Na + transporters, consistent with higher UNaV at any given BP (Fig 1B).

scholarly journals Clofibrate and di(2-ethylhexyl)phthalate increase ubiquinone contents without affecting cholesterol levels.

1994 ◽  
Vol 41 (3) ◽  
pp. 321-329
Author(s):  
F Aberg ◽  
E L Appelkvist
Keyword(s):  
Peroxisome Proliferator ◽  
Sprague Dawley ◽  
Beta Oxidation ◽  
Cholesterol Levels ◽  
Sprague Dawley Rats ◽  
Different Types ◽  
Low Toxicity ◽  
Fatty Acid Beta Oxidation ◽  
Ethylhexyl Phthalate ◽  
The Brain

Induction studies were performed on liver, muscle, heart, brain and blood by feeding Sprague-Dawley rats a diet containing a peroxisome proliferator, clofibrate or di(2-ethylhexyl)phthalate. Ingestion of these drugs resulted in an increase in the amount of two different types of ubiquinone homologues UQ9 and UQ10 found in rat. Phthalate proved to be the more effective drug, leading to a highly increased amount of ubiquinone in the liver. Increases were also found in all the above-mentioned organs except the brain. The UQ9 levels were raised to 400, 200, 120 and 120%, of the respective normal values. The antioxidant and hypolipidemic agent, probucol, was used as a control to evaluate whether the increased ubiquinone level constituted a response to the elevated hydrogen peroxide pressure, resulting from the induced increase in fatty acid beta-oxidation. In the presence of probucol, ubiquinone levels were decreased in all the above-mentioned organs except heart and brain. Probucol had limited effects on the amount of cholesterol and did not significantly alter the amount of dolichol. The two peroxisome proliferators differed in their effects on cholesterol, as well as on dolichol levels which was induced by phthalate but not by clofibrate. The possible mechanisms involved, and the importance of low toxicity drugs which could elevate ubiquinone levels in various tissues, are discussed.

Permeability of the microcirculation in area postrema of rat

1988 ◽  
Vol 46 ◽  
pp. 348-349
Author(s):  
Shams M. Ghoneim ◽  
Frank M. Faraci ◽  
Gary L. Baumbach
Keyword(s):  
Brain Stem ◽  
Area Postrema ◽  
Upper Body ◽  
Sprague Dawley ◽  
Sodium Cacodylate ◽  
Acute Hypertension ◽  
Sprague Dawley Rats ◽  
Ultrastructural Characteristics ◽  
The Brain ◽  
Adjacent Brain

The area postrema is a circumventricular organ in the brain stem and is one of the regions in the brain that lacks a fully functional blood-brain barrier. Recently, we found that disruption of the microcirculation during acute hypertension is greater in area postrema than in the adjacent brain stem. In contrast, hyperosmolar disruption of the microcirculation is greater in brain stem. The objective of this study was to compare ultrastructural characteristics of the microcirculation in area postrema and adjacent brain stem.We studied 5 Sprague-Dawley rats. Horseradish peroxidase was injected intravenously and allowed to circulate for 1, 5 or 15 minutes. Following perfusion of the upper body with 2.25% glutaraldehyde in 0.1 M sodium cacodylate, the brain stem was removed, embedded in agar, and chopped into 50-70 μm sections with a TC-Sorvall tissue chopper. Sections of brain stem were incubated for 1 hour in a solution of 3,3' diaminobenzidine tetrahydrochloride (0.05%) in 0.05M Tris buffer with 1% H2O2.

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.

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