scholarly journals Impaired sodium‐evoked paraventricular nucleus neuronal activation and blood pressure regulation in conscious Sprague–Dawley rats lacking central G α i 2 proteins

2015 ◽  
Vol 216 (3) ◽  
pp. 314-329 ◽  
Author(s):  
C. Y. Carmichael ◽  
A. C. T. Carmichael ◽  
J. T. Kuwabara ◽  
J. T. Cunningham ◽  
R. D. Wainford
Keyword(s):  
Blood Pressure ◽  
Paraventricular Nucleus ◽  
Blood Pressure Regulation ◽  
Pressure Regulation ◽  
Neuronal Activation ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

Abstract 035: Differential Sodium-evoked Activation of Pvn Magnocellular vs. Parvocellular Neurons in Rats Lacking Central GαI

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Casey Y Carmichael ◽  
Richard D Wainford
Keyword(s):  
Blood Pressure ◽  
Pressure Control ◽  
Blood Pressure Regulation ◽  
Pressure Regulation ◽  
Sprague Dawley ◽  
Significant Component ◽  
Sprague Dawley Rats ◽  
Parvocellular Neurons ◽  
Circulating Levels

Aim: To determine the role of brain Gαi 2 proteins in mediating sodium-evoked PVN neuronal activation and blood pressure regulation in conscious rats. Methods: 24-h intracerebroventricular scrambled (SCR) or Gαi 2 oligodeoxynucleotide (ODN; 25μg/5μl)-pretreated conscious Sprague-Dawley rats were monitored for changes in MAP in response to HS (IV 3M NaCl; 0.14 ml/100g). Rats were sacrificed at control (C), 10, 40, or 100-min post-HS for PVN cFos IHC and analysis of plasma AVP and NE. Separate groups received a V 1a receptor antagonist (IV; 10 μg/ml/kg) 5-min prior to HS. Results: No difference was observed in sodium-evoked peak change in MAP and MAP remained elevated at 100-min in Gαi 2 but not SCR ODN rats (MAP 100-min post-HS [mmHg] SCR 134±2 vs Gαi 2 146±3, P<0.05). Significant increases in the number of Fos + PVN magnocellular neurons were observed post-HS in SCR and Gαi 2 ODN groups ([Fos + cells] SCR C 3±1 vs 100-min 31±5; Gαi 2 C 2±0 vs 100-min 26±4, P <0.05). A rapid increase in circulating AVP was observed at 10-min in both SCR (plasma AVP [pg/mL] C 12.2±1.6 vs 10-min 62.8±6.9, P <0.05) and Gαi 2 ODN (plasma AVP [pg/mL] C 12.1±1.5 vs 10-min 67.7±7.7 P <0.05) groups and returned to control levels at 40- and 100-min. SCR ODN rats exhibited significant increases in the number of Fos + PVN parvocellular neurons ([Fos+ cells] C 15±1 vs 100-min 67±4, P <0.05) and a significant suppression in circulating NE post-HS (plasma NE [nmol/L] C 44.1±4.9 vs 10-min 17.4±3.9, P <0.05). Gαi 2 ODN rats exhibited significantly less Fos + parvocellular neurons compared to SCR ODN rats (100-min [Fos+ cells] SCR 67±4 vs Gαi 2 30±2, P <0.05) and failed to suppress circulating NE ( P >0.05). V 1a receptor blockade prevented a HS-evoked increase in MAP in SCR ODN rats while Gαi 2 ODN rats exhibited elevated MAP (MAP 100-min [mmHg] SCR 125±2 vs Gαi 2 135±0, P <0.05). Conclusion: Brain Gαi 2 proteins are required to mediate sodium-evoked parvocellular sympathetic, but not magnocellular vasopressinergic, responses to maintain physiological blood pressure regulation. A significant component of blood pressure control in this setting is regulated by the sympathetic nervous system, as supported by the attenuated activation of PVN parvocellular neurons and a failure to suppress circulating levels of NE in Gαi 2 ODN rats.

Effect of dietary cardiac glycosides on blood pressure regulation in rats

2000 ◽  
Vol 78 (7) ◽  
pp. 548-556 ◽  
Author(s):  
Masaaki Tamura ◽  
Hirotoshi Utsunomiya ◽  
Misa Nakamura ◽  
Erwin J Landon
Keyword(s):  
Blood Pressure ◽  
High Blood Pressure ◽  
Cardiac Glycosides ◽  
Extracellular Fluid ◽  
Diet Group ◽  
Blood Pressure Regulation ◽  
Pressure Regulation ◽  
Sprague Dawley ◽  
Synthetic Diet ◽  
Regular Diet

To investigate the possible physiological significance of dietary cardiac glycosides in blood pressure regulation, the blood pressure of normal Sprague Dawley rats raised on a regular diet, which naturally contains large amounts of Na+-pump inhibitors, was compared with that of rats on a purified synthetic diet, which contains no Na+-pump specific inhibitors, and with that of rats on a synthetic diet supplemented with 10 µg·mL-1 ouabain or 10 µg·mL-1 convallatoxin in the drinking water. After 6 weeks on the synthetic diet, the systolic blood pressure in the synthetic diet group was significantly elevated (145 ± 5 vs. 128 ± 4 mmHg, P < 0.05). At 10 weeks it reached a plateau (154 ± 3 vs. 122 ± 3 mmHg, P < 0.05). Plasma renin activity and Na+ level were significantly higher in animals fed synthetic diets than in the regular diet group (P < 0.01). Administration of either losartan or lisinopril or a switch to a low salt synthetic diet (0.03% sodium) normalized the synthetic diet-induced high blood pressure. Supplementation of the synthetic diet with the cardiac glycosides delayed the onset of the increase in blood pressure for 4 weeks. Plasma aldosterone levels were approximately doubled in the cardiac glycoside-treated groups. Higher plasma Na+ levels and hematocrit values present in the synthetic diet group were normalized by the glycoside supplements. These results suggest that supplemental dietary cardiac glycosides exert bidirectional effects on blood pressure regulation through actions that modulate extracellular fluid and electrolyte balance.Key words: cardiac glycosides, convallatoxin, ouabain, ouabain-like substance, purified synthetic diet, high blood pressure, renin-angiotensin system.

BDNF shifts excitatory-inhibitory balance in the paraventricular nucleus of the hypothalamus to elevate blood pressure

2021 ◽  
Author(s):  
Daniella Thorsdottir ◽  
Zachary Einwag ◽  
Benedek Erdos
Keyword(s):  
Blood Pressure ◽  
Paraventricular Nucleus ◽  
Viral Vectors ◽  
Cardiovascular Responses ◽  
Sprague Dawley ◽  
Bdnf Expression ◽  
Sprague Dawley Rats ◽  
The Central Nervous System ◽  
Inhibitory Signaling ◽  
Signaling Components

Presympathetic neurons in the paraventricular nucleus of the hypothalamus (PVN) play a key role in cardiovascular regulation. We have previously shown that brain-derived neurotrophic factor (BDNF), acting in the PVN, increases sympathetic activity and blood pressure and serves as a key regulator of stress-induced hypertensive responses. BDNF is known to alter glutamatergic and GABA-ergic signaling broadly in the central nervous system, but whether BDNF has similar actions in the PVN remains to be investigated. Here, we tested the hypothesis that increased BDNF expression in the PVN elevates blood pressure by enhancing NMDA receptor (NMDAR)- and inhibiting GABAA receptor (GABAAR)-mediated signaling. Sprague Dawley rats received bilateral PVN injections of AAV2 viral vectors expressing GFP or BDNF. Three weeks later, cardiovascular responses to PVN injections of NMDAR and GABAAR agonists and antagonists were recorded under α-chloralose-urethane anesthesia. Additionally, expressions of excitatory and inhibitory signaling components in the PVN were assessed using immunofluorescence. Our results showed that NMDAR inhibition led to a greater decrease in blood pressure in the BDNF vs GFP group, while GABAAR inhibition led to greater increases in blood pressure in the GFP group compared to BDNF. Conversely, GABAAR activation decreased blood pressure significantly more in GFP vs BDNF rats. In addition, immunoreactivity of NMDAR1 was upregulated, while GABAAR-a1 and K+/Cl- cotransporter 2 were downregulated by BDNF overexpression in the PVN. In summary, our findings indicate that hypertensive actions of BDNF within the PVN are mediated, at least in part, by augmented NMDAR and reduced GABAAR signaling.

scholarly journals Creation of the 5-hydroxytryptamine receptor 7 knockout rat as a tool for cardiovascular research

2019 ◽  
Vol 51 (7) ◽  
pp. 290-301 ◽  
Author(s):  
Elena Y. Demireva ◽  
Huirong Xie ◽  
Emma D. Flood ◽  
Janice M. Thompson ◽  
Bridget M. Seitz ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Vena Cava ◽  
Blood Pressure Regulation ◽  
Target Sequence ◽  
Pressure Regulation ◽  
Sprague Dawley ◽  
Cardiovascular Research ◽  
Exon 2 ◽  
Exon 1 ◽  
F2 Generation

Using CRISPR-Cas9 technology, we created a 5-HT7 receptor global knockout (KO) rat, on a Sprague-Dawley background, for use in cardiovascular physiology studies focused on blood pressure regulation. A stable line carrying indels in exons 1 and 2 of the rat Htr7 locus was established and validated. Surprisingly, 5-HT7 receptor mRNA was still present in the KO rat. However, extensive cDNA and genomic sequencing of KO tissues confirmed an 11 bp deletion in exon 1 and 4 bp deletion in exon 2. The exon 1 deletion resulted in a frameshifted mRNA sequence coding for a nonfunctional protein. While the Htr1B locus was a potential off-target for the guide RNAs designed for exon 2 of Htr7, there were no off-target sequence changes at this locus in the originating founder. When the F2 generation of KO was compared with wild-type (WT) counterparts, neither the male nor female KO rats were different in body size, fat weights, or mass of organs (kidney, heart, and brain) important to blood pressure. Females were smaller in mass than their counterpart males. Clinical measures of plasma from nonfasted rats revealed largely similar values, comparing WT and KO, of glucose, blood urea nitrogen, creatinine, phosphate, calcium, and albumin to name a few. Loss of a functional 5-HT7 receptor was validated by the complete loss of relaxation to the 5-HT1/7 receptor agonist 5-carboxamidotryptamine in the isolated abdominal vena cava. This newly created 5-HT7 receptor KO rat will be of use to investigate the importance of the 5-HT7 receptor in blood pressure regulation.

scholarly journals The sympathetic role of glutamatergic paraventricular nucleus neurons in blood pressure regulation

2019 ◽  
Vol 597 (6) ◽  
pp. 1433-1434
Author(s):  
J. E. Soriano ◽  
B. A. Scott ◽  
R. E. Rosentreter ◽  
B. Vaseghi
Keyword(s):  
Blood Pressure ◽  
Paraventricular Nucleus ◽  
Blood Pressure Regulation ◽  
Pressure Regulation

Evidence for endothelin involvement in the response to high salt

2001 ◽  
Vol 281 (1) ◽  
pp. F144-F150 ◽  
Author(s):  
David M. Pollock ◽  
Jennifer S. Pollock
Keyword(s):  
Blood Pressure ◽  
Receptor Activation ◽  
Blood Pressure Regulation ◽  
High Salt ◽  
Pressure Regulation ◽  
Sprague Dawley ◽  
High Salt Diet ◽  
Salt Loading ◽  
Salt Diet ◽  
Low Salt

Recent evidence suggests that endothelin-1 (ET-1), perhaps through the ETB receptor, may participate in blood pressure regulation through the control of sodium excretion. Mean arterial pressure (MAP) was continuously measured via telemetry implants in male Sprague-Dawley rats. After 1 wk of baseline measurements, rats were given either high (10%) or low (0.08%) NaCl in chow for the remainder of the experiment ( n = 5 in each group). MAP was significantly increased in rats on a high-salt diet (115 ± 2 mmHg) compared with rats on the low-salt diet (103 ± 2 mmHg; P < 0.05). All rats were then treated with the ETB receptor antagonist A-192621 mixed with the food and adjusted daily to ensure a dose of 30 mg · kg−1 · day−1. ETB blockade produced an increase in MAP within a few hours of treatment and was significantly higher in rats on the high-salt diet over a 1-wk period (170 ± 3 vs. 115 ± 3 mmHg, P < 0.01). To determine whether the increase in MAP during A-192621 treatment was due to increased ETA receptor activation, all rats were then given the ETA-selective antagonist ABT-627 in the drinking water while a low-salt/high-salt diet and ETB blockade were continued. ABT-627 decreased MAP within a few hours in rats on either the high-salt (113 ± 3 mmHg) or low-salt (101 ± 3 mmHg) diet. These results support the hypothesis that endothelin, through the ETB receptor, participates in blood pressure regulation in the response to salt loading.

scholarly journals ACE2 and ADAM17 Interaction Regulates the Activity of Presympathetic Neurons

Hypertension ◽  
2019 ◽  
Vol 74 (5) ◽  
pp. 1181-1191 ◽  
Author(s):  
Snigdha Mukerjee ◽  
Hong Gao ◽  
Jiaxi Xu ◽  
Ryosuke Sato ◽  
Andrea Zsombok ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Paraventricular Nucleus ◽  
Renin Angiotensin System ◽  
Blood Pressure Regulation ◽  
Pressure Regulation ◽  
Neurogenic Hypertension ◽  
Blood Pressure Elevation ◽  
Angiotensin System ◽  
Renin Angiotensin

Brain renin angiotensin system within the paraventricular nucleus plays a critical role in balancing excitatory and inhibitory inputs to modulate sympathetic output and blood pressure regulation. We previously identified ACE2 and ADAM17 as a compensatory enzyme and a sheddase, respectively, involved in brain renin angiotensin system regulation. Here, we investigated the opposing contribution of ACE2 and ADAM17 to hypothalamic presympathetic activity and ultimately neurogenic hypertension. New mouse models were generated where ACE2 and ADAM17 were selectively knocked down from all neurons (AC-N) or Sim1 neurons (SAT), respectively. Neuronal ACE2 deletion revealed a reduction of inhibitory inputs to AC-N presympathetic neurons relevant to blood pressure regulation. Primary neuron cultures confirmed ACE2 expression on GABAergic neurons synapsing onto excitatory neurons within the hypothalamus but not on glutamatergic neurons. ADAM17 expression was shown to colocalize with angiotensin-II type 1 receptors on Sim1 neurons, and the pressor relevance of this neuronal population was demonstrated by photoactivation. Selective knockdown of ADAM17 was associated with a reduction of FosB gene expression, increased vagal tone, and prevented the acute pressor response to centrally administered angiotensin-II. Chronically, SAT mice exhibited a blunted blood pressure elevation and preserved ACE2 activity during development of salt-sensitive hypertension. Bicuculline injection in those models confirmed the supporting role of ACE2 on GABAergic tone to the paraventricular nucleus. Together, our study demonstrates the contrasting impact of ACE2 and ADAM17 on neuronal excitability of presympathetic neurons within the paraventricular nucleus and the consequences of this mutual regulation in the context of neurogenic hypertension.

Adenoviral inhibition of AT1a receptors in the paraventricular nucleus inhibits acute increases in mean arterial blood pressure in the rat

2010 ◽  
Vol 299 (5) ◽  
pp. R1202-R1211 ◽  
Author(s):  
Carrie A. Northcott ◽  
Stephanie Watts ◽  
Yanfang Chen ◽  
Mariana Morris ◽  
Alex Chen ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Paraventricular Nucleus ◽  
Pressor Response ◽  
Marker Gene ◽  
Acute Administration ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Short Term ◽  
Arterial Blood ◽  
Sprague Dawley Rats

Brain and peripheral renin-angiotensin systems are important in blood pressure maintenance. Circulating ANG II stimulates brain RAS to contribute to the increase mean arterial pressure (MAP). This mechanism has not been fully clarified, so it was hypothesized that reducing angiotensin type 1a (AT1a) receptors (AT1aRs) in the paraventricular nucleus (PVN) would diminish intravenous ANG II-induced increases in MAP. Adenoviruses (Ad) encoding AT1a small hairpin RNA (shRNA) or Ad-LacZ (marker gene) were injected into the PVN [1 × 109 plaque-forming units/ml, bilateral (200 nl/site)] of male Sprague-Dawley rats instrumented with radiotelemetry transmitters for MAP and heart rate measurements and with venous catheters for drug administration. No differences in weight gain or basal MAP were observed. ANG II (30 ng·kg−1·min−1 iv, 15 μl/min for 60 min) was administered 3, 7, 10, and 14 days after PVN Ad injection to increase blood pressure. ANG II-induced elevations in MAP were significantly reduced in PVN Ad-AT1a shRNA rats compared with Ad-LacZ rats (32 ± 6 vs. 8 ± 9 mmHg at 7 days, 35 ± 6 vs. 10 ± 6 mmHg at 10 days, and 32 ± 2 vs. 1 ± 5 mmHg at 14 days; P < 0.05). These observations were confirmed by acute administration of losartan (20 nmol/l, 100 nl/site) in the PVN prior to short-term infusion of ANG II; the ANG II-pressor response was attenuated by 69%. In contrast, PVN Ad-AT1a shRNA treatment did not influence phenylephrine-induced increases in blood pressure (30 μg·kg−1·min−1 iv, 15 μl/min for 30 min). Importantly, PVN Ad-AT1a shRNA did not alter superior mesenteric arterial contractility to ANG II or norepinephrine; ACh-induced arterial relaxation was also unaltered. β-Galactosidase staining revealed PVN Ad transduction, and Western blot analyses revealed significant reductions of PVN AT1 protein. In conclusion, PVN-localized AT1Rs are critical for short-term circulating ANG II-mediated elevations of blood pressure. A sustained suppression of AT1aR expression by single administration of shRNA can interfere with short-term actions of ANG II.

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