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.

Plasma renin activity and forearm blood flow in paraplegic humans

1985 ◽  
Vol 59 (3) ◽  
pp. 924-927 ◽  
Author(s):  
P. R. Freund ◽  
G. L. Brengelmann
Keyword(s):  
Blood Flow ◽  
Plasma Renin Activity ◽  
Forearm Blood Flow ◽  
Control Period ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
The Body ◽  
Renin Activity ◽  
Angiotensin System ◽  
Renin Angiotensin

We recently found that paraplegic humans respond to hyperthermia with subnormal increase in skin blood flow (SkBF), based on measurements of forearm blood flow (FBF). Is this inhibition of SkBF a defect in thermoregulation or a cardiovascular adjustment necessary for blood pressure control? Since high resting plasma renin activity (PRA) is found in unstressed individuals with spinal cord lesions and since PRA increases during hyperthermia in normal humans, we inquired whether the renin-angiotensin system is responsible for the attenuated FBF in hyperthermic resting paraplegics. Five subjects, 28–47 yr, with spinal transections (T1-T10), were heated in water-perfused suits. Blood samples for PRA determinations were collected during a control period and after internal temperature reached approximately 38 degrees C. Some subjects with markedly attenuated FBF had little or no elevation of PRA; those with the best-developed FBF response exhibited the highest PRA. Clearly, circulating angiotensin is not the agent that attenuates SkBF. Rather, increased activity of the renin-angiotensin system may be a favorable adaptation that counters the locally mediated SkBF increase in the lower body and thus allows controlled active vasodilation in the part of the body subject to centrally integrated sympathetic effector outflow.

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.

scholarly journals The ACE2/Angiotensin-(1–7)/MAS Axis of the Renin-Angiotensin System: Focus on Angiotensin-(1–7)

2018 ◽  
Vol 98 (1) ◽  
pp. 505-553 ◽  
Author(s):  
Robson Augusto Souza Santos ◽  
Walkyria Oliveira Sampaio ◽  
Andreia C. Alzamora ◽  
Daisy Motta-Santos ◽  
Natalia Alenina ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Renin Angiotensin System ◽  
The Body ◽  
Biologically Active ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
The Past ◽  
The Brain ◽  
System Focus

The renin-angiotensin system (RAS) is a key player in the control of the cardiovascular system and hydroelectrolyte balance, with an influence on organs and functions throughout the body. The classical view of this system saw it as a sequence of many enzymatic steps that culminate in the production of a single biologically active metabolite, the octapeptide angiotensin (ANG) II, by the angiotensin converting enzyme (ACE). The past two decades have revealed new functions for some of the intermediate products, beyond their roles as substrates along the classical route. They may be processed in alternative ways by enzymes such as the ACE homolog ACE2. One effect is to establish a second axis through ACE2/ANG-(1–7)/MAS, whose end point is the metabolite ANG-(1–7). ACE2 and other enzymes can form ANG-(1–7) directly or indirectly from either the decapeptide ANG I or from ANG II. In many cases, this second axis appears to counteract or modulate the effects of the classical axis. ANG-(1–7) itself acts on the receptor MAS to influence a range of mechanisms in the heart, kidney, brain, and other tissues. This review highlights the current knowledge about the roles of ANG-(1–7) in physiology and disease, with particular emphasis on the brain.

The Effects of the Antagonists of the Renin—Angiotensin System on Cardiovascular Response to Lower-Body Subatmospheric Pressure in the Anaesthetized Cat

1980 ◽  
Vol 58 (6) ◽  
pp. 549-552 ◽  
Author(s):  
S. A. Adigun ◽  
D. P. Clough ◽  
J. Conway ◽  
R. Hatton
Keyword(s):  
Blood Pressure ◽  
Arterial Blood Pressure ◽  
Negative Pressure ◽  
Cardiovascular Response ◽  
Venous Pressure ◽  
Renin Angiotensin System ◽  
Lower Body ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Arterial Blood

1. Lower-body subatmospheric (negative) pressure led to a prompt reduction in central venous pressure and arterial blood pressure. Arterial blood pressure was then restored within 30 s and there was a tachycardia. These reflex responses have been used to investigate the role angiotensin plays in blood pressure control. 2. The initial plasma renin activity (2.9 ng of angiotensin I h−1 ml−1) did not change during the brief lowering of pressure. Before pressure was lowered neither the angiotensin-converting enzyme inhibitor nor a competitive antagonist, [Sar1,Ala8]-angiotensin II, lowered arterial pressure. 3. Nevertheless, after inhibition of the renin-angiotensin system by these agents, the reduction in blood pressure induced by lower-body negative pressure became greater and the blood pressure recovery was impaired. 4. The findings suggest that angiotensin, at a blood concentration which has no direct effect on blood pressure, interacts with the sympathetic nervous system to maintain arterial blood pressure.

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.

Effect of oral contraceptives on the renin angiotensin system and renal function

2001 ◽  
Vol 280 (3) ◽  
pp. R807-R813 ◽  
Author(s):  
Amrit K. Kang ◽  
John A. Duncan ◽  
Daniel C. Cattran ◽  
John S. Floras ◽  
Vesta Lai ◽  
...  
Keyword(s):  
Lower Body Negative Pressure ◽  
Renal Plasma Flow ◽  
Premenopausal Women ◽  
Renin Angiotensin System ◽  
Renin Secretion ◽  
Control Group ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Active Renin

We examined the effect of oral contraceptive (OC) usage on the renin angiotensin system (RAS) in two related experiments. In the first experiment, subjects were 34 healthy, normotensive, premenopausal women, 15 OC users and 19 OC nonusers, mean age 25 ± 1 yr, ingesting a controlled sodium diet. We assessed arterial pressure, glomerular filtration rate, effective renal plasma flow, renal vascular resistance (RVR), and filtration fraction (FF) using inulin and p-aminohippurate clearance techniques, both at baseline and in response to the ANG II receptor blocker losartan. In the second experiment, in similar subjects, 10 OC users and 10 nonusers, we examined circulating RAS components [angiotensinogen, ANG II, aldosterone, plasma renin activity (PRA), and active renin] in response to incremental lower body negative pressure (LBNP), to determine whether renin secretion is suppressed by OC usage. OC users exhibited elevations in systolic blood pressure, RVR, and FF compared with nonusers, which were partially corrected by losartan. In the LBNP phase of the study, baseline measures of PRA, angiotensinogen, ANG II, and aldosterone were all increased in the OC group compared with the control group. Active renin levels did not differ between groups. Incremental LBNP resulted in increased circulating levels of RAS components in both groups. We conclude that the RAS is activated in women using OCs. There was no evidence that decreases in renin secretion result in normalization of the RAS as a whole.

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.

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.

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