Autonomic control of the heart is altered in Sprague-Dawley rats with spontaneous hydronephrosis

The renal medulla plays an important role in cardiovascular regulation, through interactions with the autonomic nervous system. Hydronephrosis is characterized by substantial loss of renal medullary tissue. However, whether alterations in autonomic control of the heart are observed in this condition is unknown. Thus we assessed resting hemodynamics and baroreflex sensitivity (BRS) for control of heart rate in urethane/chloralose-anesthetized Sprague-Dawley rats with normal or hydronephrotic kidneys. While resting arterial pressure was similar, heart rate was higher in rats with hydronephrosis (290 ± 12 normal vs. 344 ± 11 mild/moderate vs. 355 ± 13 beats/min severe; P < 0.05). The evoked BRS to increases, but not decreases, in pressure was lower in hydronephrotic rats (1.06 ± 0.06 normal vs. 0.72 ± 0.10 mild/moderate vs. 0.63 ± 0.07 ms/mmHg severe; P < 0.05). Spectral analysis methods confirmed reduced parasympathetic function in hydronephrosis, with no differences in measures of indirect sympathetic activity among conditions. As a secondary aim, we investigated whether autonomic dysfunction in hydronephrosis is associated with activation of the renin-angiotensin system (RAS). There were no differences in circulating angiotensin peptides among conditions, suggesting that the impaired autonomic function in hydronephrosis is independent of peripheral RAS activation. A possible site for angiotensin II-mediated BRS impairment is the solitary tract nucleus (NTS). In normal and mild/moderate hydronephrotic rats, NTS administration of the angiotensin II type 1 receptor antagonist candesartan significantly improved the BRS, suggesting that angiotensin II provides tonic suppression to the baroreflex. In contrast, angiotensin II blockade produced no significant effect in severe hydronephrosis, indicating that at least within the NTS baroreflex suppression in these animals is independent of angiotensin II.

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Effects of dietary salt on angiotensin peptides in kidney.

Journal of the American Society of Nephrology ◽

10.1681/asn.v641209 ◽

1995 ◽

Vol 6 (4) ◽

pp. 1209-1215

Author(s):

Q C Meng ◽

J Durand ◽

Y F Chen ◽

S Oparil

Keyword(s):

Angiotensin Ii ◽

Spontaneously Hypertensive Rats ◽

Spontaneously Hypertensive Rat ◽

Sprague Dawley ◽

Dietary Salt ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Angiotensin Peptides ◽

Sprague Dawley Rats ◽

Wistar Kyoto

This study used a novel simple method for the extraction, separation, identification, and quantitation of angiotensin-like immunoactivity from tissue to examine the effects of altering dietary NaCl intake on intrarenal angiotensin I, II, and III levels in salt-sensitive, spontaneously hypertensive rats, salt-resistant Wistar-Kyoto rats, and Sprague-Dawley rats. Seven-week-old male spontaneously hypertensive rats, Wistar-Kyoto rats, and Sprague-Dawley rats were assigned randomly to a diet containing either 8% (high) or 1% (basal) salt and were maintained on these diets for 3 wk. Rats were then decapitated without prior anesthesia, and kidneys were rapidly (< 30 s) removed, snap frozen in liquid nitrogen, and stored at -80 degrees C. Frozen tissue was extracted in 2 M acetic acid and then subjected to solid-phase extraction with the cation exchange resin AG 50W X4. Angiotensin peptides were separated by reversed-phase high-performance liquid chromatography on a phenyl silica gel column with an eluent consisting of 20% acetonitrile in 0.1 M ammonium phosphate buffer, pH 4.9, and quantitated by radioimmunoassay. The elution of standard peptides under isocratic conditions revealed clear resolution of angiotensin I, II, and III and the (1-7) and (3-8) peptides. Recoveries of both labeled and unlabeled angiotensin peptide standards from the extraction step were > 90%. Renal angiotensin II stores were significantly higher in spontaneously hypertensive rats than in Wistar-Kyoto or Sprague-Dawley rats, independent of diet. Renal angiotensin II and III were further suppressed during dietary salt supplementation in both salt-resistant strains but not in the spontaneously hypertensive rat. These findings are consistent with an enhanced (compared with Wistar-Kyoto and Sprague-Dawley rats) role for angiotensin II in the kidney of the salt-sensitive, spontaneously hypertensive rat, particularly under conditions of dietary salt supplementation.

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Angiotensin-(1-12) is an alternate substrate for angiotensin peptide production in the heart

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00175.2008 ◽

2008 ◽

Vol 294 (5) ◽

pp. H2242-H2247 ◽

Cited By ~ 61

Author(s):

Aaron J. Trask ◽

Jewell A. Jessup ◽

Mark C. Chappell ◽

Carlos M. Ferrario

Keyword(s):

Angiotensin Ii ◽

Cardiac Tissue ◽

Renin Angiotensin System ◽

Biologically Active ◽

Sprague Dawley ◽

Angiotensin I ◽

Spontaneously Hypertensive ◽

Angiotensin Peptides ◽

Wistar Kyoto ◽

Alternate Substrate

Identification of angiotensin-(1-12) as an intermediate precursor derived directly from angiotensinogen led us to explore whether the heart has the capacity to process angiotensin-(1-12) into biologically active angiotensin peptides. The generation of angiotensin I, angiotensin II, and angiotensin-(1-7) from exogenous angiotensin-(1-12) was evaluated in the effluent of isolated perfused hearts mounted on a Langendorff apparatus in three normotensive and two hypertensive strains: Sprague-Dawley, Lewis, congenic mRen2.Lewis, Wistar-Kyoto, and spontaneously hypertensive rats. Hearts were perfused with Krebs solution for 60 min before and after the addition of angiotensin-(1-12) (10 nmol/l). Angiotensin-(1-12) caused the rapid appearance of both angiotensin I and angiotensin II in the perfusate that peaked between 30 and 60 min of recirculation. Production of angiotensin-(1-7) from exogenous angiotensin-(1-12) rose steadily over the course of the 60-min experiment. These data directly demonstrate that angiotensin-(1-12) is a substrate for the formation of angiotensin peptides in cardiac tissue. This finding further suggests that this angiotensinogen-derived product is a previously unrecognized important precursor peptide to the renin-angiotensin system cascade.

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A novel mechanism for angiotensin II formation in streptozotocin-diabetic rat glomeruli

AJP Renal Physiology ◽

10.1152/ajprenal.00159.2003 ◽

2005 ◽

Vol 288 (6) ◽

pp. F1183-F1190 ◽

Cited By ~ 64

Author(s):

Rekha Singh ◽

Ashok K. Singh ◽

David J. Leehey

Keyword(s):

Angiotensin Ii ◽

Renin Angiotensin System ◽

Diabetic Rats ◽

Diabetic Rat ◽

Ang Ii ◽

Sprague Dawley ◽

New Information ◽

Sprague Dawley Rats ◽

And Control

Recent evidence suggests that the intrarenal renin-angiotensin system (RAS) may play an important role in the development of glomerular changes associated with diabetic nephropathy. In this study, the glomerular RAS was examined in male Sprague-Dawley rats made diabetic with streptozotocin (STZ), and the findings compared with those obtained in control nondiabetic rats. In diabetic rat glomerular extracts, angiotensinogen and angiotensin II (ANG II) levels were increased significantly by 2.2- and 1.9-fold, respectively, compared with nondiabetic controls. No significant differences in ANG I and angiotensin-converting enzyme (ACE) levels were observed between these groups. The HPLC analysis of the glomerular extracts demonstrated that exogenous ANG I was converted into various ANG peptides including ANG II, ANG(1–9), and ANG(1–7). A significant increase in formation of ANG II from exogenous ANG I was observed in STZ rats compared with control rats. Preincubation of glomerular extracts with captopril resulted in a 20–30% decrease in ANG II conversion from exogenous ANG I in diabetic and control rats. The possible role of ANG(1–9) in formation of ANG II was examined by HPLC. Exogenous ANG(1–9) in glomerular extracts was converted into ANG II, this conversion being significantly higher in STZ rats than in control rats. These findings provide new information that ANG(1–9) is produced in rat glomerular extracts, can be converted to ANG II, and that this conversion is also stimulated in diabetic rat glomeruli. Thus this study demonstrates that in diabetic rats, glomerular ANG II levels are increased due to an increase in angiotensinogen and an increase in the formation of ANG II.

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Renal haemodynamic and tubular actions of urotensin II in the rat

Journal of Endocrinology ◽

10.1677/joe-08-0260 ◽

2008 ◽

Vol 198 (3) ◽

pp. 617-624 ◽

Cited By ~ 15

Author(s):

Alaa E S Abdel-Razik ◽

Ellen J Forty ◽

Richard J Balment ◽

Nick Ashton

Keyword(s):

Body Weight ◽

Renal Medulla ◽

Fractional Excretion ◽

Haemodynamic Effects ◽

Urotensin Ii ◽

Sprague Dawley ◽

Minimal Impact ◽

Sprague Dawley Rats ◽

Fractional Excretion Of Sodium ◽

Excretion Rates

Urotensin II (UTS) is a potent vasoactive peptide that was originally identified in teleost fish. Mammalian orthologues of UTS and its receptor (UTSR) have been described in several species, including humans and rats. We have shown previously that bolus injections of UTS caused a decrease in urine flow and sodium excretion rates in parallel with marked reductions in renal blood flow (RBF) and glomerular filtration rate (GFR). The aim of this study was to determine the effect of UTS infusion at a dose that has minimal impact upon renal haemodynamics in order to identify a potential direct tubular action of UTS. Infusion of rat UTS (rUTS) at 0.6 pmol/min per 100 g body weight in male Sprague–Dawley rats, which had no effect on RBF and caused a 30% reduction in GFR, resulted in a significant increase in the fractional excretion of sodium (vehicle 2.3±0.6 versus rUTS 0.6 pmol 4.5±0.6%, P<0.05) and potassium. At the higher dose of 6 pmol/min per 100 g body weight, haemodynamic effects dominated the response. rUTS induced a marked reduction in RBF and GFR (vehicle 1.03±0.06 versus rUTS 6 pmol 0.31±0.05 ml/min per 100 g body weight, P<0.05) resulting in an anti-diuresis and anti-natriuresis, but no change in fractional excretion of sodium or potassium. Uts2d and Uts2r mRNA expression were greater in the renal medulla compared with the cortex. Together, these data support an inhibitory action of Uts2d on renal tubule sodium and potassium reabsorption in the rat, in addition to its previously described renal haemodynamic effects.

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Androgens augment proximal tubule transport

AJP Renal Physiology ◽

10.1152/ajprenal.00188.2003 ◽

2004 ◽

Vol 287 (3) ◽

pp. F452-F459 ◽

Cited By ~ 70

Author(s):

Albert Quan ◽

Sumana Chakravarty ◽

Jian-Kang Chen ◽

Jian-Chun Chen ◽

Samer Loleh ◽

...

Keyword(s):

Angiotensin Ii ◽

Proximal Tubule ◽

Specific Binding ◽

Extracellular Volume ◽

Renin Angiotensin System ◽

Angiotensin Receptors ◽

Sprague Dawley ◽

Angiotensin System ◽

Renin Angiotensin

The proximal tubule contains an autonomous renin-angiotensin system that regulates transport independently of circulating angiotensin II. Androgens are known to increase expression of angiotensinogen, but the effect of androgens on proximal tubule transport is unknown. In this in vivo microperfusion study, we examined the effect of androgens on proximal tubule transport. The volume reabsorptive rate in Sprague-Dawley rats given dihydrotestosterone (DHT) injections was significantly higher than in control rats given vehicle injections (4.57 ± 0.31 vs. 3.31 ± 0.23 nl·min−1·mm−1, P < 0.01). Luminally perfusing with either enalaprilat (10−4 M) to inhibit production of angiotensin II or losartan (10−8 M) to block the angiotensin receptor decreased the proximal tubule volume reabsorptive rate in DHT-treated rats to a significantly greater degree than in control vehicle-injected rats. The renal expression of angiotensinogen was shown to be higher in the DHT-treated animals, using Northern blot analysis. The expression of angiotensin receptors, determined by specific binding of angiotensin II, was not different in the two groups of animals. Brush-border membrane protein abundance of the Na/H exchanger, a membrane transport protein under angiotensin II regulation, was also higher in DHT-treated rats vs. control rats. Rats that received DHT had higher blood pressures than the control rats but had no change in their glomerular filtration rate. In addition, serum angiotensin II levels were lower in DHT-treated vs. control rats. These results suggest that androgens may directly upregulate the proximal tubule renin-angiotensin system, increase the volume reabsorptive rate, and thereby increase extracellular volume and blood pressure and secondarily decrease serum angiotensin II levels.

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