The effect of hypothalamo-pituitary disconnection on the renin-angiotensin system in the late-gestation fetal sheep

2005 ◽  
Vol 288 (5) ◽  
pp. R1279-R1287 ◽  
Author(s):  
Kai Chen ◽  
Luke C. Carey ◽  
Jingfang Liu ◽  
Nancy K. Valego ◽  
Stephen B. Tatter ◽  
...  
Keyword(s):  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Fetal Tissue ◽  
Late Gestation ◽  
Receptor Subtype ◽  
Postnatal Life ◽  
Ang Ii ◽  
Fetal Sheep ◽  
Angiotensin System ◽  
Renin Angiotensin

The activity of the renin-angiotensin system (RAS) increases significantly in the late-gestation fetal sheep. Fetal cortisol is also increased during this time, and it is thought that the increase in cortisol may modulate the RAS changes. Previous studies have examined the effects of cortisol infusion on RAS activity, but the effects of blocking the peripartum increase in cortisol concentrations on the developmental changes in the RAS are not known. Therefore, we utilized the technique of hypothalamic-pituitary disconnection (HPD), which prevents the cortisol surge from occurring, to investigate the importance of the late-gestation increase in cortisol on the ontogenic changes in RAS activity. HPD of fetal sheep was performed at 120 days of gestational age (dGA), and fetuses were delivered between 135 and 139 dGA. Control fetuses were sham operated. HPD blocked the late-gestation cortisol increase but did not alter renal renin mRNA, renal renin or prorenin protein content, nor plasma renin levels compared with sham operated. However, HPD fetuses had increased ANG II receptor subtype 1 (AT1) mRNA and protein expression in the kidney and lungs. ANG II receptor subtype 2 (AT2) expression was not altered in these tissues at either mRNA or protein level. HPD did not change AT1 or AT2 mRNA in the left ventricle but did result in decreased protein levels for both receptors. These studies demonstrate that blockade of the naturally occurring increase in fetal cortisol concentration in late gestation is associated with tissue-specific alterations in expression of AT1 and AT2 receptors. These changes may impact on fetal tissue maturation and hence have consequences in postnatal life.

The kidney is resistant to chronic hypoglycaemia in late-gestation fetal sheep

2007 ◽  
Vol 85 (6) ◽  
pp. 597-605 ◽  
Author(s):  
Amanda C. Boyce ◽  
Karen J. Gibson ◽  
E. Marelyn Wintour ◽  
Irene Koukoulas ◽  
Kathryn L. Gatford ◽  
...  
Keyword(s):  
Renal Function ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Late Gestation ◽  
Mrna Levels ◽  
Fetal Sheep ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Insulin Levels ◽  
Igf I

We imposed a sustained reduction in glucose supply to late-gestation fetal sheep to see whether the reduction in glucose and insulin levels affected renal growth, renin expression and synthesis, and renal function. Maternal glucose concentrations were lowered to 1.7–1.9 mmol/L for 12–13 days by i.v. insulin infusion (n = 9, 121 days gestation, term = 150 days). Control ewes (n = 7) received vehicle. Maternal and fetal glucose concentrations were 40% and 31% lower than in controls (p < 0.001), respectively. Fetal plasma insulin levels fell 36% ± 7% by day 7 (p < 0.05); IGF-I levels were unchanged. Arterial PO2 and pH increased and PCO2 fell (p < 0.05). Renal function was largely unaffected. Longitudinal growth was 28% slower and spleen weights were 36% smaller (p < 0.05); body and kidney weights were not affected. Renal renin levels and renin, angiotensinogen, and angiotensin receptor mRNA levels were similar to those of controls. Plasma renin levels increased from 2.1 ± 0.6 to 7.6 ± 2.8 ng angiotensin I·mL–1·h–1 (p = 0.01). Thus reductions in fetal glucose and insulin levels in late gestation that were sufficient to retard skeletal growth had no effect on kidney growth or function or the renal renin–angiotensin system, possibly because IGF-I levels were not reduced. There was, however, increased activity of the circulating renin–angiotensin system similar to that seen during insulin-induced hypoglycaemia.

Role of renin-angiotensin system in response to hemorrhage in fetal sheep

1981 ◽  
Vol 240 (6) ◽  
pp. H848-H854 ◽  
Author(s):  
H. S. Iwamoto ◽  
A. M. Rudolph
Keyword(s):  
Venous Blood ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Fetal Life ◽  
Fetal Sheep ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Plasma Angiotensin ◽  
Blood Pressures ◽  
Placental Blood

During fetal life, the autonomic nervous system is not fully mature, and it is likely that hormonal mechanisms play an important role in controlling cardiovascular function. In chronically instrumented fetal sheep, hemorrhage increased plasma renin activity and plasma angiotensin concentration significantly from 6.7 +/- 2.5 to 15.2 +/- 3.1 ng.ml-1.h-1 and from 74 +/- 19 to 182 +/- 43 pg/ml, respectively. Both mean arterial and venous blood pressures decreased initially from 45 to 35 Torr and from 3.5 to 2.5 Torr, respectively; then both returned to control values. Fetal heart rate decreased initially from 174 beats/min and then increased to 186 beats/min. To determine whether angiotensin had a role in mediating these responses to hemorrhage, we hemorrhaged a second group of fetuses before and during infusion of saralasin, a competitive antagonist of angiotensin. Hemorrhage during infusion of saralasin decreased heart rat from 170 to 145 beats/min and further decreased mean arterial pressure to 30 Torr. Cardiac output decreased from 436 +/- 25 to 368 +/- 30 ml.min-1.kg-1, and umbilical-placental blood flow decreased from 205 +/- 20 to 145 +/- 10 ml.min-1.kg-1. We conclude that the renin-angiotensin system plays a major role in the response to hemorrhage in fetal sheep.

Postnatal development of the renin-angiotensin system in rats

1980 ◽  
Vol 238 (5) ◽  
pp. R432-R437 ◽  
Author(s):  
K. B. Wallace ◽  
J. B. Hook ◽  
M. D. Bailie
Keyword(s):  
Steady State ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Rat Plasma ◽  
Neonatal Rat ◽  
Postnatal Life ◽  
Renin Substrate ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Age Related

The purpose of this investigation was to correlate the development of the various enzyme activities associated with the renin-angiotensin system with age-related differences in the steady-state concentrations of angiotensin I (AI) and II (AII). Angiotensin was quantified by radioimmunoassay. Plasma renin activity and concentration increased between birth and 3 wk of age, and declined thereafter to adult values. Renal renin content, on the other hand, increased throughout the first 6 wk of postnatal life. The concentration of AII in plasma also increased following birth; however, maximum concentrations were not attained until 5 wk of age. In contrast, plasma AI did not increase between 3 and 6 wk of age. These data suggest that the steady-state concentration of AII in neonatal rat plasma may be partially limited by the low plasma renin substrate concentration. The increase in AII between 3 and 6 wk of age may reflect the increasing converting enzyme activity.

Characterization of the renin-angiotensin system in the turtle Pseudemys scripta

1984 ◽  
Vol 247 (1) ◽  
pp. R15-R23 ◽  
Author(s):  
M. D. Cipolle ◽  
J. E. Zehr
Keyword(s):  
Pressor Response ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Ang Ii ◽  
Freshwater Turtles ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Fourfold Increase ◽  
Inactive Form ◽  
Pseudemys Scripta

Studies were conducted in freshwater turtles Pseudemys scripta to define some characteristics of the renin-angiotensin system in this reptile. Dialyzed acid-treated kidney extract (1 g tissue per ml water) produced a prolonged pressor response in unanesthetized turtles, which was eliminated by boiling the extract or by pretreating the turtle with [Sar1, Ile8]angiotensin II. A rat pressor assay was employed because turtle angiotensin (ANG) was bound poorly by the anti-[Asp1, Ile5, His9]ANG I used in our radioimmunoassay. Kidney extract incubated with homologous plasma (pH 5.5 and 25 degrees C) produced a time-dependent pressor response in rats. The pressor activity of the product was eliminated by dialysis or by pretreating the rats with [Sar1, Ile8]ANG II. The pressor response in anesthetized turtles to ANG I was significantly reduced by captopril, whereas the ANG II response remained unchanged, thus demonstrating the presence of ANG-converting enzyme activity in these animals. We determined the velocity of turtle ANG formation at various dilutions of enzyme (kidney extract) or substrate (plasma). Turtle kidney extract incubated with homologous plasma displayed typical Michaelis-Menten kinetics. Finally we conducted experiments to determine whether a portion of turtle plasma renin exists in an inactive form. Trypsinization caused a slight increase in plasma renin activity (PRA), whereas acidification to pH 3.3 yielded a fourfold increase in PRA.

Upregulation of renin-angiotensin system and downregulation of kallikrein in obstructive nephropathy

1993 ◽  
Vol 264 (5) ◽  
pp. F874-F881 ◽  
Author(s):  
S. S. el-Dahr ◽  
J. Gee ◽  
S. Dipp ◽  
B. G. Hanss ◽  
R. C. Vari ◽  
...  
Keyword(s):  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Obstructive Nephropathy ◽  
Mrna Levels ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Kininase Ii ◽  
Plasma Angiotensin ◽  
Renin Mrna

The purpose of this study was to delineate the effects of prolonged (1 and 5 wk) unilateral ureteral obstruction (UUO) on the intrarenal renin-angiotensin and kallikrein-kinin systems in the rat. Systolic blood pressure (SBP) and plasma angiotensin (ANG) II levels were significantly higher at 1 and 5 wk of obstruction than in sham-operated groups. Also, plasma renin activity and ANG I levels were elevated at 1 wk (P < 0.05), and plasma angiotensin-converting enzyme (ACE)-kininase II activity was elevated at 5 wk (P < 0.05). Blockade of ANG II receptors with losartan (Dup 753) prevented the rise in SBP after UUO and normalized SBP in chronically hypertensive UUO rats. Renin mRNA levels and ANG II content were elevated in the obstructed kidneys at 1 and 5 wk compared with sham-operated kidneys (P < 0.05). ACE-kininase II activity was elevated in both the obstructed and contralateral kidneys at 5 wk compared with sham-operated kidneys (P < 0.05). In marked contrast to renin, total immunoreactive kallikrein contents and tissue kallikrein mRNA levels in the obstructed kidneys were reduced to 25% of sham-operated kidneys both at 1 and 5 wk (P < 0.001). The results indicate that urinary obstruction activates renin and suppresses kallikrein gene expression. Activation of ACE-kininase II by UUO also serves to enhance intrarenal ANG II generation and kinin degradation. The results implicate ANG II overproduction and kinin deficiency in the pathogenesis of UUO-induced hypertension and intrarenal vasoconstriction.

Nonimmune hydrops fetalis and activation of the renin-angiotensin system after asphyxia in preterm fetal sheep

2001 ◽  
Vol 280 (4) ◽  
pp. R1045-R1051 ◽  
Author(s):  
Eugenie R. Lumbers ◽  
Alistair J. Gunn ◽  
David Y. Zhang ◽  
June J. Wu ◽  
Linda Maxwell ◽  
...  
Keyword(s):  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Hydrops Fetalis ◽  
Mrna Levels ◽  
Fetal Sheep ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Tissue Edema ◽  
Nonimmune Hydrops ◽  
Sheep Fetus

This study examined the hypothesis that the development of hydrops fetalis after asphyxia in the 0.6 gestation sheep fetus would be associated with activation of the fetal renin-angiotensin system (RAS). Fetuses were randomly assigned to either sham occlusion ( n = 7) or to 30 min of asphyxia induced by complete umbilical cord occlusion for 30 min ( n = 8). Asphyxia led to severe bradycardia and hypotension that resolved after release of occlusion. After occlusion, plasma renin concentration was significantly increased in the asphyxia group compared with controls ( P < 0.005) after 3 min (16.3 ± 5.3 vs. 4.1 ± 1.3 ng · ml−1 · h−1), and 72 h (30.6 ± 6.3 vs. 3.7 ± 1.2 ng · ml−1 · h−1). Renal renin concentrations and mRNA levels were significantly greater in the asphyxia group after 72 h of recovery. All fetuses in the asphyxia group showed generalized tissue edema, ascites, and pleural effusions after 72 h of recovery. In conclusion, asphyxia in the preterm fetus caused sustained activation of the RAS, which was associated with hydrops fetalis.

Renal renin-angiotensin system in diabetes: functional, immunohistochemical, and molecular biological correlations

1993 ◽  
Vol 265 (4) ◽  
pp. F477-F486 ◽  
Author(s):  
S. Anderson ◽  
F. F. Jung ◽  
J. R. Ingelfinger
Keyword(s):  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Hydraulic Pressure ◽  
Ang Ii ◽  
Glomerular Injury ◽  
Renal Vasculature ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Ace Activity ◽  
Immunohistochemical Studies

Recent evidence indicates a role for the renin-angiotensin system (RAS) in the pathogenesis of glomerular injury in diabetes. To further explore the RAS in diabetes, studies were conducted in nondiabetic control rats and in moderately hyperglycemic diabetic (DM) rats. In DM rats, both acute and chronic therapy with the specific angiotensin II (ANG II) receptor antagonist losartan did not affect glomerular hyperfiltration or hyperperfusion but selectively normalized the glomerular capillary hydraulic pressure and ultrafiltration coefficient. To determine the basis of intrarenal hemodynamic responsiveness to RAS inhibition, we conducted biochemical, molecular biological, and immunohistochemical studies to assess endogenous RAS activity. Values for plasma renin concentration and serum angiotensin-converting enzyme (ACE) activity in DM rats were normal. In contrast, intrarenal renin protein content, and renin and angiotensinogen mRNAs, were increased in DM rats, suggesting disproportionate activation of the intrarenal RAS. Total renal ACE activity was significantly reduced in DM rats, but immunohistochemical studies indicated redistribution of ACE in the diabetic kidney. Proximal tubule ACE activity was reduced, but ACE immunostaining intensity was enhanced in glomeruli and renal vasculature. Together, these observations indicate increased RAS activity in those sites (glomeruli and vasculature) most likely to regulate hemodynamic function, potentially explaining the prominent responses to pharmacological blockade of ANG II formation and/or action.

Low LBNP tolerance in men is associated with attenuated activation of the renin-angiotensin system

2000 ◽  
Vol 279 (3) ◽  
pp. R822-R829 ◽  
Author(s):  
John E. Greenleaf ◽  
Trine Welløw Petersen ◽  
Anders Gabrielsen ◽  
Bettina Pump ◽  
Peter Bie ◽  
...  
Keyword(s):  
Lower Body Negative Pressure ◽  
Venous Pressure ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
The Body ◽  
Ang Ii ◽  
Lower Body ◽  
Central Venous ◽  
Angiotensin System ◽  
Renin Angiotensin

Plasma vasoactive hormone concentrations [epinephrine (pEpi), norepinephrine (pNE), ANG II (pANG II), vasopressin (pVP), endothelin-1 (pET-1)] and plasma renin activity (pRA) were measured periodically and compared during lower body negative pressure (LBNP) to test the hypothesis that responsiveness of the renin-angiotensin system, the latter being one of the most powerful vasoconstrictors in the body, is of major importance for LBNP tolerance. Healthy men on a controlled diet (2,822 cal/day, 2 mmol · kg−1· day−1 Na+) were exposed to 30 min of LBNP from −15 to −50 mmHg. LBNP was uneventful for seven men [25 ± 2 yr, high-tolerance (HiTol) group], but eight men (26 ± 3 yr) reached presyncope after 11 ± 1 min [ P < 0.001, low-tolerance (LoTol) group]. Mean arterial pressure (MAP) did not change measurably, but central venous pressure and left atrial diameter decreased similarly in both groups (5–6 mmHg, by ≈30%, P < 0.05). Control (0 mmHg LBNP) hormone concentrations were similar between groups, however, pRAdiffered between them (LoTol 0.6 ± 0.1, HiTol 1.2 ± 0.1 ng ANG I · ml−1 · h−1, P < 0.05). LBNP increased ( P < 0.05) pRA and pANG II, respectively, more in the HiTol group (9.9 ± 2.2 ng ANG I · ml−1· h−1 and 58 ± 12 pg/ml) than in LoTol subjects (4.3 ± 0.9 ng ANG I · ml−1 · h−1 and 28 ± 6 pg/ml). In contrast, the increase in pVP was higher ( P < 0.05) in the LoTol than in the HiTol group. The increases ( P < 0.05) for pNE were nonsignificant between groups, and pET-1 remained unchanged. Thus there may be a causal relationship between attenuated activation of pRA and pANG II and presyncope, with pVP being a possible cofactor. Measurement of resting pRA may be of predictive value for those with lower hypotensive tolerance.

Isoproterenol-induced cardiac hypertrophy: role of circulatory versus cardiac renin-angiotensin system

2001 ◽  
Vol 281 (6) ◽  
pp. H2410-H2416 ◽  
Author(s):  
Frans H. H. Leenen ◽  
Roselyn White ◽  
Baoxue Yuan
Keyword(s):  
Cardiac Hypertrophy ◽  
Enzyme Inhibitor ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Left Ventricular ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Male Wistar Rats ◽  
Β Receptor

To assess the possible contribution of the circulatory and cardiac renin-angiotensin system (RAS) to the cardiac hypertrophy induced by a β-agonist, the present study evaluated the effects of isoproterenol, alone or combined with an angiotensin I-converting enzyme inhibitor or AT1 receptor blocker, on plasma and LV renin activity, ANG I, and ANG II, as well as left ventricular (LV) and right ventricular (RV) weight. Male Wistar rats received isoproterenol by osmotic minipump subcutaneously and quinapril or losartan once daily by gavage. Plasma and LV ANGs were measured by radioimmunoassay after separation by HPLC. Isoproterenol alone decreased blood pressure, more markedly when combined with losartan or quinapril. Isoproterenol significantly increased LV and RV weight and total collagen. Neither losartan nor quinapril inhibited the increases in LV or RV weight. Losartan prevented the increase in RV collagen but enhanced the increase in LV collagen. Isoproterenol increased plasma renin, ANG I, and ANG II three- to fourfold. Isoproterenol combined with losartan or quinapril, caused marked further increases except for a significant decrease in plasma ANG II with quinapril. Isoproterenol alone did not increase LV ANG II and, combined with losartan or quinapril, actually decreased LV ANG II. These results indicate that isoproterenol-induced cardiac hypertrophy is associated with clear increases in plasma ANG II, but not in LV ANG II. Both losartan and quinapril lower LV ANG II below control levels, but do not prevent the isoproterenol-induced cardiac hypertrophy. These findings do not support a role for the circulatory or cardiac RAS in the cardiac trophic responses to β-receptor stimulation.

scholarly journals Renin knockout rat: control of adrenal aldosterone and corticosterone synthesis in vitro and adrenal gene expression

2015 ◽  
Vol 308 (1) ◽  
pp. R73-R77 ◽  
Author(s):  
Hershel Raff ◽  
Ashley Gehrand ◽  
Eric D. Bruder ◽  
Matthew J. Hoffman ◽  
William C. Engeland ◽  
...  
Keyword(s):  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Immunohistochemical Analysis ◽  
Zona Glomerulosa ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Aldosterone Production ◽  
Renin Mrna

The classic renin-angiotensin system is partly responsible for controlling aldosterone secretion from the adrenal cortex via the peptide angiotensin II (ANG II). In addition, there is a local adrenocortical renin-angiotensin system that may be involved in the control of aldosterone synthesis in the zona glomerulosa (ZG). To characterize the long-term control of adrenal steroidogenesis, we utilized adrenal glands from renin knockout (KO) rats and compared steroidogenesis in vitro and steroidogenic enzyme expression to wild-type (WT) controls (Dahl S rat). Adrenal capsules (ZG; aldosterone production) and subcapsules [zona reticularis/fasciculata (ZFR); corticosterone production] were separately dispersed and studied in vitro. Plasma renin activity and ANG II concentrations were extremely low in the KO rats. Basal and cAMP-stimulated aldosterone production was significantly reduced in renin KO ZG cells, whereas corticosterone production was not different between WT and KO ZFR cells. As expected, adrenal renin mRNA expression was lower in the renin KO compared with the WT rat. Real-time PCR and immunohistochemical analysis showed a significant decrease in P450aldo ( Cyp11b2) mRNA and protein expression in the ZG from the renin KO rat. The reduction in aldosterone synthesis in the ZG of the renin KO adrenal seems to be accounted for by a specific decrease in P450aldo and may be due to the absence of chronic stimulation of the ZG by circulating ANG II or to a reduction in locally released ANG II within the adrenal gland.

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