Abstract P616: Evidence That The Extracellular Domain Of Na + /K + Atpase Is The Receptor For Cyclic Gmp-Induced Natriuresis

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Brandon A Kemp ◽  
John J Gildea ◽  
Nancy L Howell ◽  
Susanna R Keller ◽  
Robert M Carey
Keyword(s):  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Control Period ◽  
Extracellular Domain ◽  
Sprague Dawley ◽  
Binding Studies ◽  
Urine Sodium ◽  
Sprague Dawley Rats ◽  
Normal Rat ◽  
Change In Mean

Previous studies from our laboratory have shown that extracellular renal interstitial (RI) cyclic guanosine 3’5’-monophosphate (cGMP) increases urine sodium (Na + ) excretion (U Na V) at the renal proximal tubule (RPT) in rats via activation of Src family kinase. Extracellular cGMP engenders this response through an unknown receptor. We hypothesized that cGMP binds to the extracellular domain of Na + /K + -ATPase (NKA) on basolateral membranes of RPT cells inhibiting Na + transport. In the present study, we evaluated the effect of RI infusion of rostafuroxin (RF), a digitoxigenin derivative that specifically displaces oubain (OUA) binding from NKA, on U Na V in the presence of RI cGMP infusion. Volume expanded, uninephrectomized, 12-week-old female Sprague-Dawley rats received RI infusions of vehicle (D 5 W) (N=8), RI cGMP (18, 36, and 72 μg/kg/min; each dose for 30 min; N=10), or RI cGMP + RF (0.012 μg/kg/min; N=5) for 90 min following a 30 min control period with RI infusion of vehicle D 5 W. RI cGMP infusion induced a significant natriuresis from 0.39 ± 0.06 μmol/min to 1.03 ± 0.21 (P<0.05), 1.17 ± 0.19 (P<0.01), and 1.94 ± 0.16 (P<0.001) μmol/min at 18, 36, and 72 μg/kg/min cGMP, respectively. RI co-infusion of cGMP + RF abolished the cGMP-induced natriuresis at all doses (F=16.05, P<0.001). There was no change in mean arterial pressure during any infusion. To further demonstrate that cGMP binds to NKA, we performed a series of competitive binding studies in isolated RPTs from normal rat kidneys (N=4 for each) with bodipy-OUA (2 μM) + cGMP (10 μM) and 8-[Biotin]-AET-cGMP (2 μM) + OUA (10 μM). In the presence of cGMP, bodipy-OUA fluorescence intensity was reduced from 1422.1 ± 63 to 1072.5 ± 64 relative fluorescent units (RFU, P<0.01). In the presence of OUA, 8-[Biotin]-AET-cGMP staining was reduced from 1916.3 ± 144 to 1492.2 ± 84 RFU (P<0.05). Serving as control, biotinylated cAMP (N=2) did not demonstrate any fluorescence above background. Together, these data suggest that cGMP may compete with RF for binding on NKA and that the extracellular domain of NKA may serve as the receptor for cGMP-induced natriuresis.

Arginine vasopressin-induced natriuresis in the anaesthetized rat: involvement of V1 and V2 receptors

1993 ◽  
Vol 136 (2) ◽  
pp. 283-288 ◽  
Author(s):  
C. P. Smith ◽  
R. J. Balment
Keyword(s):  
Angiotensin Ii ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Arginine Vasopressin ◽  
Plasma Concentrations ◽  
Receptor Subtypes ◽  
Vasopressin Receptor ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Anaesthetized Rat

ABSTRACT The present study was undertaken to determine the involvement of the two established vasopressin receptor subtypes (V1 and V2) in arginine vasopressin (AVP)-induced natriuresis and also to determine whether changes in mean arterial pressure (MAP) and/or the renally active hormones atrial natriuretic peptide (ANP), angiotensin II (AII) and aldosterone are a prerequisite for the expression of AVP-induced natriuresis. In Sprague–Dawley rats which were anaesthetized with Inactin (5-ethyl-5-(1′-methylpropyl)-2-thiobarbiturate) and infused with 0·077 mol NaCl/l, infusion of 63 fmol AVP/min was found to be natriuretic whereas an approximately equipotent dose of the specific V2 agonist [deamino-cis1, d-Arg8]-vasopressin (dDAVP) did not induce natriuresis. The specific V1 antagonist [β-mercapto-β,β-cyclopenta-methylene-propionyl1, O-Me-Tyr2, Arg8]-vasopressin when administered prior to infusion of 63 fmol AVP/min did not inhibit AVP-induced natriuresis. AVP-induced natriuresis was not accompanied by changes in MAP or in the plasma concentrations of the renally active hormones ANP, AII or aldosterone. These results suggest that neither the V1 nor the V2 receptor subtypes are involved in AVP-induced natriuresis. In addition, it was found that changes in MAP, plasma ANP, All or aldosterone concentrations were not a prerequisite for AVP-induced natriuresis. Journal of Endocrinology (1993) 136, 283–288

Area postrema: essential for support of arterial pressure after hemorrhage in rats

1990 ◽  
Vol 258 (6) ◽  
pp. R1472-R1478 ◽  
Author(s):  
K. M. Skoog ◽  
M. L. Blair ◽  
C. D. Sladek ◽  
W. M. Williams ◽  
M. L. Mangiapane
Keyword(s):  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Data Acquisition ◽  
Area Postrema ◽  
Plasma Renin ◽  
Base Line ◽  
Sprague Dawley ◽  
Time Period ◽  
Sprague Dawley Rats

Previous studies have indicated that the area postrema (AP) of the rat is necessary for the development of chronic angiotensin-dependent hypertension. The present study assesses the role of the AP in the maintenance of arterial pressure during hemorrhage. Sprague-Dawley rats were given sham or AP lesions 1 wk before the experiment. They were instrumented with femoral arterial and venous catheters 2 days before the experiment. On the day of the experiment, base-line mean arterial pressure (MAP) was measured for 1 h before hemorrhage. During the following 45 min, each rat was subjected to one 7-ml/kg hemorrhage every 15 min for a total of three hemorrhages. MAP was monitored by computerized data acquisition. As shown previously, MAP was slightly but significantly lower in AP-lesion rats compared with sham-lesion rats before the hemorrhage procedure. In AP-lesion rats, hemorrhage resulted in a significantly greater fall in arterial pressure than in sham-lesion rats. In spite of larger drops in pressure in AP-lesion rats, hemorrhage caused equivalent increases in plasma renin and vasopressin in both groups. In AP-lesion rats compared with sham-lesion rats, significant bradycardia was present before hemorrhage. Hemorrhage caused bradycardia in both sham- and AP-lesion rats relative to the prehemorrhage heart rates, but AP-lesion rats showed greater bradycardia than did sham-lesion rats during every time period. We conclude that the AP may play an important role in the defense of arterial pressure against hemorrhage.

Effects of arterial hypotension on microvascular oxygen exchange in contracting skeletal muscle

2006 ◽  
Vol 100 (3) ◽  
pp. 1019-1026 ◽  
Author(s):  
Brad J. Behnke ◽  
Danielle J. Padilla ◽  
Leonardo F. Ferreira ◽  
Michael D. Delp ◽  
Timothy I. Musch ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Contractile Function ◽  
Muscle Blood Flow ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Exercise Onset ◽  
Muscle Contractile ◽  
Hypovolemic Hypotension

In healthy animals under normotensive conditions (N), contracting skeletal muscle perfusion is regulated to maintain microvascular O2 pressures (Pmv[Formula: see text]) at levels commensurate with O2 demands. Hypovolemic hypotension (H) impairs muscle contractile function; we tested whether this condition would alter the matching of O2 delivery (Q̇o2) to O2 utilization (V̇o2), as determined by Pmv[Formula: see text] at the onset ofmuscle contractions. Pmv[Formula: see text] in the spinotrapezius muscles of seven female Sprague-Dawley rats (280 ± 6 g) was measured every 2 s across the transition from rest to 1-Hz twitch contractions. Measurements were made under N (mean arterial pressure, 97 ± 4 mmHg) and H (induced by arterial section; mean arterial pressure, 58 ± 3 mmHg, P < 0.05) conditions; Pmv[Formula: see text] profiles were modeled using a multicomponent exponential fitted with independent time delays. Hypotension reduced muscle blood flow at rest (24 ± 8 vs. 6 ± 1 ml−1·min−1·100 g−1 for N and H, respectively; P < 0.05) and during contractions (74 ± 20 vs. 22 ± 4 ml−1·min−1·100 g−1 for N and H, respectively; P < 0.05). H significantly decreased resting Pmv[Formula: see text] and steady-state contracting Pmv[Formula: see text](19.4 ± 2.4 vs. 8.7 ± 1.6 Torr for N and H, respectively, P < 0.05). At the onset of contractions, H reduced the time delay (11.8 ± 1.7 vs. 5.9 ± 0.9 s for N andH, respectively, P < 0.05) before the fall in Pmv[Formula: see text] and accelerated therate of Pmv[Formula: see text] decrease (time constant, 12.6 ± 1.4 vs. 7.3 ± 0.9 s for N and H, respectively, P < 0.05). Muscle V̇o2 was reduced by 71% at rest and 64% with contractions in H vs. N, and O2 extraction during H averaged 78% at rest and 94% during contractions vs. 51 and 78% in N. These results demonstrate that H constrains the increase of skeletal muscle Q̇o2 relative to that of V̇o2 at the onset of contractions,leading to a decreased Pmv[Formula: see text]. According to Fick's law, this scenario will decrease blood-myocyte O2 flux, thereby slowing V̇o2 kinetics and exacerbating the O2 deficit generated at exercise onset.

scholarly journals Chronic renal artery insulin infusion increases mean arterial pressure in male Sprague-Dawley rats

2018 ◽  
Vol 314 (1) ◽  
pp. F81-F88 ◽  
Author(s):  
Debra L. Irsik ◽  
Jian-Kang Chen ◽  
Michael W. Brands
Keyword(s):  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Renal Artery ◽  
Insulin Infusion ◽  
Plasma Renin ◽  
Urinary Sodium Excretion ◽  
Experimental Models ◽  
Sprague Dawley ◽  
Novel Approach ◽  
Sprague Dawley Rats

Hyperinsulinemia has been hypothesized to cause hypertension in obesity, type 2 diabetes, and metabolic syndrome through a renal mechanism. However, it has been challenging to isolate renal mechanisms in chronic experimental models due, in part, to technical difficulties. In this study, we tested the hypothesis that a renal mechanism underlies insulin hypertension. We developed a novel technique to permit continuous insulin infusion through the renal artery in conscious rats for 7 days. Mean arterial pressure increased by ~10 mmHg in rats that were infused intravenously (IV) with insulin and glucose. Renal artery doses were 20% of the intravenous doses and did not raise systemic insulin levels or cause differences in blood glucose. The increase in blood pressure was not different from the IV group. Mean arterial pressure did not change in vehicle-infused rats, and there were no differences in renal injury scoring due to the renal artery catheter. Glomerular filtration rate, plasma renin activity, and urinary sodium excretion did not differ between groups at baseline and did not change significantly with insulin infusion. Thus, by developing a novel approach for chronic, continuous renal artery insulin infusion, we provided new evidence that insulin causes hypertension in rats through actions initiated within the kidney.

Chronic Lability of Arterial Pressure in the Rat Does Not Evolve into Hypertension

1980 ◽  
Vol 59 (s6) ◽  
pp. 405s-407s ◽  
Author(s):  
W. T. Talman ◽  
D. R. Alonso ◽  
D. J. Reis
Keyword(s):  
Heart Rate ◽  
Standard Deviation ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Histopathological Changes ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Electrolytic Lesions ◽  
The Mean ◽  
Catecholamine Neurons

1. In rats, electrolytic lesions of the A2 group of catecholamine neurons result in lability of arterial pressure without hypertension. 2. To establish whether labile arterial pressure, when chronic, will lead to fixed hypertension, we placed lesions in the A2 area of adult male Sprague-Dawley rats and measured mean arterial pressure, heart rate and their variability (expressed as the standard deviation) 11 months later. Controls were age-matched, unoperated or sham-operated rats. 3. In rats with A2 lesions: (a) the mean arterial pressure was lower (103 ± 7.5 mmHg; n = 6; P&lt;0.05) than in sham-operated (123 ± 4.7 mmHg; n = 4) or unoperated (120 ± 3.1 mmHg; n = 9) controls; (b) the standard deviation of mean arterial pressure was higher (16 ± 1.8 mmHg; P&lt;0.001) than in sham-operated (5 ± 0.7 mmHg) or unoperated controls (7 ± 0.6 mmHg); (c) the mean and standard deviation of heart rate did not differ between groups. No histopathological changes were detected in the A2 group. 4. Chronic lability of arterial pressure does not evolve into sustained hypertension nor does it induce systemic lesions.

C5-blocking antibody reduces fluid requirements and improves responsiveness to fluid infusion in hemorrhagic shock managed with hypotensive resuscitation

2007 ◽  
Vol 102 (2) ◽  
pp. 673-680 ◽  
Author(s):  
Russell M. Peckham ◽  
Michael T. Handrigan ◽  
Timothy B. Bentley ◽  
Michael J Falabella ◽  
Andrew D. Chrovian ◽  
...  
Keyword(s):  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Hemorrhagic Shock ◽  
Fold Increase ◽  
Sprague Dawley ◽  
Blocking Antibody ◽  
Fluid Infusion ◽  
Hypotensive Resuscitation ◽  
Sprague Dawley Rats ◽  
Prolonged Hypotension

Hypotensive resuscitation strategies and inhibition of complement may both be of benefit in hemorrhagic shock. We asked if C5-blocking antibody (anti-C5) could diminish the amount of fluid required and improve responsiveness to resuscitation from hemorrhage. Awake, male Sprague-Dawley rats underwent controlled hemorrhage followed by prolonged (3 h) hypotensive resuscitation with lactated Ringer’s or Hextend, with or without anti-C5. Anti-C5 treatment led to an estimated 62.3 and 58.5% reduction in the volume of Hextend and lactated Ringer’s, respectively. In the subgroup of animals with a positive mean arterial pressure (MAP) response to fluid infusion following prolonged hypotension, anti-C5 treatment led to an estimated 4.7- and 4.1-fold increase in mean arterial pressure response per unit Hextend and lactated Ringer’s infused, respectively. We observed no significant postresuscitation metabolic differences between the anti-C5 groups and controls. Whether anti-C5 could serve as a volume-sparing adjunct that improves responsiveness to fluid administration in humans deserves further study.

BIOASSAY OF GROWTH HORMONE

1974 ◽  
Vol 75 (4) ◽  
pp. 669-682 ◽  
Author(s):  
K.-G. Thorngren ◽  
L. I. Hansson
Keyword(s):  
Growth Hormone ◽  
Bone Growth ◽  
Control Period ◽  
Growth Stimulation ◽  
Sprague Dawley ◽  
Hormone Administration ◽  
Sprague Dawley Rats ◽  
Hypophysectomized Rats ◽  
Operative Control ◽  
Sensitivity Specificity

ABSTRACT The growth stimulating effect of growth hormone was determined with tetracycline as intravital marker of the longitudinal bone growth of proximal tibia in female Sprague-Dawley rats hypophysectomized at 60 days of age. After a post-operative control period of 15 days growth hormone (NIH-GH-B16) was given daily for 5 or 10 days followed by a 10 day period after its withdrawal. L-thyroxine was given in association with the growth hormone administration to potentiate the growth stimulation. A linear log dose-response relation was found for the two administration models with a high precision. The thyroxine-treatment increased the sensitivity of the bioassay. An administration period of 5 days was found sufficient for the bioassay of growth hormone in thyroxine-treated hypophysectomized rats. Compared with the earlier bioassay methods for growth hormone, the present bioassay is more favourable when all the factors, such as precision, sensitivity, specificity, and administration period are considered.

scholarly journals Mild DOCA-salt hypertension: sympathetic system and role of renal nerves

2011 ◽  
Vol 300 (5) ◽  
pp. H1781-H1787 ◽  
Author(s):  
Sachin S. Kandlikar ◽  
Gregory D. Fink
Keyword(s):  
Control Period ◽  
Whole Body ◽  
Renal Nerves ◽  
Experimental Hypertension ◽  
Sympathetic Activation ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Salt Hypertension ◽  
Hypertension Development

Excess sympathetic nervous system activity (SNA) is linked to human essential and experimental hypertension. To test whether sympathetic activation is associated with a model of deoxycorticosterone acetate (DOCA)-salt hypertension featuring two kidneys and a moderate elevation of blood pressure, we measured whole body norepinephrine (NE) spillover as an index of global SNA. Studies were conducted in chronically catheterized male Sprague-Dawley rats drinking water containing 1% NaCl and 0.2% KCl. After a 7-day surgical recovery and a 3-day control period, a DOCA pellet (50 mg/kg) was implanted subcutaneously in one group of rats (DOCA), while the other group underwent sham implantation (Sham). NE spillover was measured on control day 2 and days 7 and 14 after DOCA administration or sham implantation. During the control period, mean arterial pressure (MAP) was similar in Sham and DOCA rats. MAP was significantly increased in the DOCA group compared with the Sham group after DOCA administration ( day 14: Sham = 109 ± 5.3, DOCA = 128 ± 3.6 mmHg). However, plasma NE concentration, clearance, and spillover were not different in the two groups at any time. To determine whether selective sympathetic activation to the kidneys contributes to hypertension development, additional studies were performed in renal denervated (RDX) and sham-denervated (Sham-DX) rats. MAP, measured by radiotelemetry, was similar in both groups during the control and DOCA treatment periods. In conclusion, global SNA is not increased during the development of mild DOCA-salt hypertension, and fully intact renal nerves are not essential for hypertension development in this model.

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