scholarly journals PVN Gαi 2 protein‐gated signal transduction ‐ a renal nerve dependent mechanism required for sodium homeostasis and blood pressure regulation in Sprague‐Dawley rats

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Richard David Wainford ◽  
Jill Toshiko Kuwabara
Keyword(s):  
Blood Pressure ◽  
Signal Transduction ◽  
Blood Pressure Regulation ◽  
Pressure Regulation ◽  
Sprague Dawley ◽  
Renal Nerve ◽  
Sodium Homeostasis ◽  
Sprague Dawley Rats ◽  
Dependent Mechanism

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.

scholarly journals Role of the afferent renal nerves in sodium homeostasis and blood pressure regulation in rats

2019 ◽  
Vol 104 (8) ◽  
pp. 1306-1323 ◽  
Author(s):  
Alissa A. Frame ◽  
Casey Y. Carmichael ◽  
Jill T. Kuwabara ◽  
J. Thomas Cunningham ◽  
Richard D. Wainford
Keyword(s):  
Blood Pressure ◽  
Blood Pressure Regulation ◽  
Renal Nerves ◽  
Pressure Regulation ◽  
Sodium Homeostasis

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.

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.

Abstract 121: Afferent Renal Nerve Chemo- and Mechanosensitive Responses and the Modulation of Sodium Homeostasis and Blood Pressure

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Alissa A Frame ◽  
Casey Y Carmichael ◽  
Kathryn R Walsh ◽  
Richard D Wainford
Keyword(s):  
Blood Pressure ◽  
Constant Infusion ◽  
Renal Nerves ◽  
Neuronal Activation ◽  
Sprague Dawley ◽  
Nerve Activity ◽  
Renal Nerve ◽  
Sodium Homeostasis ◽  
Sd Rats ◽  
Renal Nerve Activity

Aim: We hypothesize that challenges to sodium homeostasis differentially activate chemo- vs. mechanosensitive afferent renal nerves to evoke sympathoinhibition, sodium homeostasis and normotension in the Sprague-Dawley (SD) rat. Methods: Conscious SD rats, post sham (S) or afferent renal nerve ablation (Renal-CAP; capsaicin 33 mM) underwent IV volume expansion (VE; 5% BW) or IV sodium loading (1M NaCl Infusion – constant infusion volume) and HR, MAP, natriuresis and PVN neuronal activation (c-Fos expression) were assessed (N=4/gp). Naïve SD rats were fed a 0.6% (NS) or 4% NaCl (HS) diet for 21 days and afferent renal nerve activity was assessed as norepinephrine (NE) (1250 pmol) and NaCl-evoked (450mM) substance P (SP) release in a renal pelvic assay (N=4/gp). Radiotelemetered SD rats post S or Renal-CAP immediately prior a 0.6% (NS) or 4% NaCl (HS) diet underwent continuous MAP monitoring. On day-21 plasma and renal NE content was assessed (N=5/group). Results: Renal-CAP attenuated the natriuretic and PVN parvocellular responses to IV VE (peak UNaV [μeq/min]; S 43±4 vs Renal-CAP 26±6, P<0.05, PVN Medial Parvocellular neuronal activation [c-fos positive cells]; S 49±6 vs Renal-CAP 22±5 P<0.05) and evoked increased MAP (MAP 90min post-VE [mmHg] S 118±3 vs Renal-CAP 132±4, P<0.05). In contrast Renal-CAP did not alter the natriuresis to IV 1M NaCl (UNaV [μeq/min]; S 21±4 vs Renal-CAP 21±3) or increase MAP. In naïve SD rats HS-intake did not alter MAP and suppressed plasma and renal NE (P<0.05). HS intake increased NE, but not NaCl, mediated afferent renal nerve activity (NE-evoked peak ΔSP [ng/ml); NS 14±2, HS 22±3, P<0.05, NaCl-evoked peak ΔSP [ng/ml]; NS 17±3, HS 16±2). Renal-CAP immediately prior to a HS-intake persistently increased MAP (Day 21 MAP [mmHg] S HS 106±4, Renal-CAP HS 123±5, P<0.05) and attenuated HS-evoked global and renal sympathoinhibition (P<0.05). Conclusion: The mechanosensitive afferent renal nerves mediate acute natriuresis and blood pressure regulation via activation of PVN sympathoinhibitory neurons. During HS intake the afferent renal nerves counter the development of salt-sensitive hypertension via a mechanism involving increased mechano but not chemosensitive afferent nerve responsiveness to potentiate sympathoinhibition.

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.

Sign in / Sign up

Export Citation Format

Share Document