Angiotensin II regulates the metabolism but not the secretion of vasoactive intestinal peptide in the rabbit

1992 ◽  
Vol 83 (5) ◽  
pp. 557-560 ◽  
Author(s):  
R. E. Davis ◽  
G. J. MacDonald ◽  
K. A. Duggan

1. We have previously demonstrated that the metabolism and secretion of vasoactive intestinal peptide are affected by both acute and chronic dietary sodium. Sodium concentrations in portal and systemic plasma were unaffected by differing levels of sodium intake or administration of an acute gastric sodium load. We sought, therefore, to determine whether other hormones involved in sodium homoeostasis (such as angiotensin II) might be involved in regulating the metabolism and secretion of vasoactive intestinal peptide. We determined the metabolic clearance rate and theoretical secretion rate of vasoactive intestinal peptide in rabbits on low sodium (high circulating angiotensin II) and high sodium (low circulating angiotensin II) diets with and without simultaneous angiotensin II infusion. 2. The metabolic clearance rate of vasoactive intestinal peptide was significantly higher in rabbits on the high sodium diet during both vehicle control (P<0.01) and angiotensin II (P<0.05) infusion. Angiotensin II infusion decreased the metabolism of vasoactive intestinal peptide in rabbits on both low (P<0.01) and high (P<0.01) sodium diets. 3. Although there was a significant difference in secretion rates between the two dietary groups (P<0.025) under basal conditions, infusion of angiotensin II did not alter the secretion rate significantly in either group. 4. We conclude that angiotensin II regulates the metabolism of vasoactive intestinal peptide in the rabbit, but does not regulate its secretion.

1995 ◽  
Vol 89 (3) ◽  
pp. 267-271 ◽  
Author(s):  
K. A. Duggan ◽  
D. M. Jones ◽  
V. Z. C. Ye ◽  
R. E. Davis ◽  
G. J. MacDonald

1. In this study, we sought to determine the effect of endopeptidase 24.11 inhibition on the rate of metabolism of vasoactive intestinal peptide. The effect of such inhibition on the concentration of vasoactive intestinal peptide in two tissues was also investigated. 2. Male Sprague—Dawley rats were given the endopeptidase 24.11 blocker UK77,568 (10 mg/kg) or vehicle as a single intravenous injection or as a daily injection for 4 days. Two hours after the final or single injection, the rats were anaesthetized and blood was sampled to determine plasma concentrations of vasoactive intestinal peptide and angiotensin II. The hearts and kidneys were harvested and snap-frozen in liquid nitrogen. The plasma and tissue concentrations of vasoactive intestinal peptide and the plasma concentration of angiotensin II were determined by radioimmunoassay. In a separate group of experiments, male Sprague—Dawley rats were anaesthetized and carotid and jugular catheters were inserted. One hour after intravenous administration of UK77,568 or vehicle, an infusion of vasoactive intestinal peptide (10 pmol min−1 kg−1) was commenced via the jugular catheter. Blood was sampled to determine the vasoactive intestinal peptide concentration 1 h after commencing the vasoactive intestinal peptide infusion to calculate the metabolic clearance rate. 3. Plasma vasoactive intestinal peptide increased after acute (P < 0.05) but not chronic administration of UK77,568, while the concentration of vasoactive intestinal peptide in the heart increased after chronic administration (P < 0.0005). The concentration of vasoactive intestinal peptide in the kidney was unchanged after both acute and chronic endopeptidase 24.11 blockade. Plasma angiotensin II decreased significantly in the chronic group (P < 0.05). The metabolic clearance rate of vasoactive intestinal peptide decreased significantly after UK77,568 administration (P < 0.05). 4. These studies add to the existing indirect evidence that endopeptidase 24.11 may metabolize vasoactive intestinal peptide in addition to a number of other hormones.


1968 ◽  
Vol 42 (3) ◽  
pp. 425-432 ◽  
Author(s):  
V. JENSEN ◽  
N. DESHPANDE ◽  
R. D. BULBROOK ◽  
T. W. DOOUSS

SUMMARY The production rate of cortisol in patients with early or advanced breast cancer was compared with that of controls of comparable age. The miscible pool of this hormone was raised in advanced breast-cancer patients due to a higher production rate. The plasma clearance of cortisol remained unaffected, resulting in a higher titre of cortisol (both total and unbound) in advanced breast-cancer patients. There was no significant difference in the production rate between the early breast-cancer cases and controls. The binding of cortisol to transcortin was studied in all cases. The amount of unbound cortisol was raised in advanced breast-cancer cases. There was a significant correlation between both total and unbound cortisol and the production rate of this hormone. The latter correlation suggests that there is no abnormality in the hepatic extraction of cortisol in these patients. The metabolic clearance rate was found to be of the order of the blood flow through the liver when unbound cortisol was used for its estimation, showing that it is the unbound cortisol which is removed by the liver.


1969 ◽  
Vol 26 (7) ◽  
pp. 1789-1799 ◽  
Author(s):  
Edward M. Donaldson ◽  
Ulf H. M. Fagerlund

Gonadectomized female sockeye salmon (Oncorhynchus nerka) were injected intramuscularly with cortisol, estradiol, estradiol cypionate, or peanut oil for 8 weeks. The metabolic clearance rate of cortisol was determined by the single injection technique and calculated from the formula for a two pool system. The cortisol secretion rate was determined from the metabolic clearance rate and the plasma cortisol concentration.The volume of distribution of cortisol in the inner compartment (V1) and the outer compartment (V2), the metabolic clearance rate (MCR), the resting secretion rate (S), and the resting plasma cortisol concentration were all significantly higher in the estradiol-injected group than in the peanut oil-injected control group, and the plasma cortisol concentration at the end of the experiment was lower. V1, MCR, and S were also significantly higher in the estradiol cypionate-injected group. There were no significant differences between the cortisol-injected group and the peanut oil-injected control group or in the biological half life of cortisol between any groups.There were no significant changes in the red colour of the flesh or in body weight during the experiment. However, the cortisol-injected group did show the largest weight loss.


1994 ◽  
Vol 171 (3) ◽  
pp. 668-679 ◽  
Author(s):  
Ronald R. Magness ◽  
Kay Cox ◽  
Charles R. Rosenfeld ◽  
Norman F. Gant

1982 ◽  
Vol 100 (4) ◽  
pp. 606-612 ◽  
Author(s):  
F. Elsaesser ◽  
K. Stickney ◽  
G. Foxcroft

Abstract. A continuous infusion technique of either [3H]oestradiol-17β (E2) or unlabelled E2 was used to investigate suggested differences in the metabolic clearance rate of oestradiol-17β (MCR-E2) in immature and peripubertal female pigs. Using the isotope infusion technique, the following values were obtained: 60 day old gilts; MCR-E2 = 2133 ± 274 ([unk] ± sem) ml/min, MCR-E2/kg BW = 116 ± 14.5 ml/min kg, and conversion ratio (CR) of E2 to oestrone (E1) = 31.6 ± 3.7%. The respective values for 160 day old gilts were: MCR-E2 = 3027 ± 340, MCR-E2/kg BW = 48.5 ± 4.82, and CR = 15.9 ± 2.12. Except for a significant difference in the weight related MCR-E2 data for the 60 day old group, similar values were found following infusion of unlabelled E2. The percentage of radioactivity extractable with ether from plasma was 22.6 ± 3.0% and 27.2 ± 2.0%. Fifty-seven and 66% of total radioactivity infused was recovered in the urine within 12 h in 60 and 160 day old gilts, respectively. There was no difference in the percentage binding of E2 to plasma proteins as determined by equilibrium dialysis (80%). It is concluded that in addition to an activation of ovarian steroidogenesis during puberty, a gradual maturational decrease in the MCR-E2/kg BW might play a role in raising plasma E2 concentrations and thus in constituting an effective oestrogen feedback signal, which results in the first pre-ovulatory LH-surge.


1978 ◽  
Vol 235 (1) ◽  
pp. E74
Author(s):  
H A Schut ◽  
G J Pepe ◽  
J D Townsley

Serum concentrations of dehydroepiandrosterone (D) are greater and those of D sulfate (DS) are lower in female baboons than in women, suggesting interspecies differences in relative production and catabolism of these steroids. To examine this possibility, the metabolic clearance rate (MCR), interconversion (rho), and production of D and DS were determined in five adult female baboons by constant intravenous infusion of [3H]DS and [14C]D. MCR-D (mean +/- SE) was greater (407 +/- 72.8 1/day; 23.1 +/- 3.4 1/day.kg, P less than 0.01) than MCR-DS (44 +/- 5.7 1/day; 2.5 +/- 0.3 1/day.kg). rho-D leads to DS (mean % +/- SE) was greater (45.4 +/- 3.0, P less than 0.001) than rhoDS leads to D (3.8 +/- 0.6), indicating that the equilibrium favors DS formation. Calculated D production and secretion rates were similar (4.5 and 4.4 microgram/min, respectively), whereas DS production (4.1 microgram/min) was twice its secretion rate (2.1 microgram/min). The large difference between MCR-D and MCR-DS resembles that in human beings. However, when clearance is expressed per kilogram body weight, MCR-D is similar to that in man, but MCR-DS is approximately 15-fold greater in the baboon. It is concluded that compared to values in human beings, the greater MCR-DS in baboons maintains the lower serum DS concentration, whereas the higher serum D levels probably result from the relatively greater secretion rate of D baboons.


1979 ◽  
Vol 82 (3) ◽  
pp. 409-415 ◽  
Author(s):  
C. E. GROSVENOR ◽  
N. S. WHITWORTH

The prolactin concentration in the plasma of lactating rats rose less rapidly and attained a significantly lower plateau level in response to suckling on day 20–21 of lactation than it did on day 13–14 of lactation. Neither differences in suckling stimulation of the older pups nor a higher metabolic clearance rate (MCR) of prolactin were implicated in the reduced prolactin concentration seen in the late-lactating rats. The MCR was, in fact, slightly reduced in both conscious and late-lactating rats anaesthetized with urethane when compared with those in mid-lactation. The MCR of prolactin was not significantly altered by urethane anaesthesia in rats on either day of lactation. However, the secretion rate of prolactin, computed from the MCR multiplied by the equilibrum concentration of prolactin during suckling, was considerably reduced (665 to 392 ng/min) from mid- to late lactation. We conclude from these data that the reduced plasma concentration of prolactin in response to suckling in late lactation is the result of an impairment within the prolactin secretory mechanism.


2011 ◽  
Vol 211 (1) ◽  
pp. 47-54 ◽  
Author(s):  
Vincent Ricchiuti ◽  
Nathalie Lapointe ◽  
Luminita Pojoga ◽  
Tham Yao ◽  
Loc Tran ◽  
...  

Liberal or high-sodium (HS) intake, in conjunction with an activated renin–angiotensin–aldosterone system, increases cardiovascular (CV) damage. We tested the hypothesis that sodium intake regulates the type 1 angiotensin II receptor (AT1R), mineralocorticoid receptor (MR), and associated signaling pathways in heart tissue from healthy rodents. HS (1.6% Na+) and low-sodium (LS; 0.02% Na+) rat chow was fed to male healthy Wistar rats (n=7 animals per group). Protein levels were assessed by western blot and immunoprecipitation analysis. Fractionation studies showed that MR, AT1R, caveolin-3 (CAV-3), and CAV-1 were located in both cytoplasmic and membrane fractions. In healthy rats, consumption of an LS versus a HS diet led to decreased cardiac levels of AT1R and MR. Decreased sodium intake was also associated with decreased cardiac levels of CAV-1 and CAV-3, decreased immunoprecipitation of AT1R–CAV-3 and MR–CAV-3 complexes, but increased immunoprecipitation of AT1R/MR complexes. Furthermore, decreased sodium intake was associated with decreased cardiac extracellular signal-regulated kinase (ERK), phosphorylated ERK (pERK), and pERK/ERK ratio; increased cardiac striatin; decreased endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS (peNOS), but increased peNOS/eNOS ratio; and decreased cardiac plasminogen activator inhibitor-1. Dietary sodium restriction has beneficial effects on the cardiac expression of factors associated with CV injury. These changes may play a role in the cardioprotective effects of dietary sodium restriction.


1990 ◽  
Vol 124 (2) ◽  
pp. 215-223 ◽  
Author(s):  
S. Harvey ◽  
H. Klandorf ◽  
C. G. Scanes

ABSTRACT Surgical thyroidectomy increases basal and TRH-induced GH concentrations in the peripheral plasma of immature domestic fowl. Replacement therapy with thyroxine (T4; 100 μg/kg per day for 7 days, i.m.) suppressed the GH responses to thyroidectomy. Bolus administration of T4 (10 μg/kg, i.m.) to thyroidectomized birds promptly lowered the circulating GH concentrations, which remained suppressed for at least 4 h. Chronic (daily injections for 7 days) or acute (one injection) pretreatment of thyroidectomized birds with iopanoic acid (IOP; 40 mg/bird, i.m.) before the bolus administration of T4 attenuated, but did not prevent, inhibition of circulating GH levels by T4. Administration of IOP (40 mg/bird i.m.) 24 h and immediately before the administration of tri-iodothyronine (T3; 3 μg/kg, i.m.) or T4 (10 μg/kg, i.m.) also failed to suppress thyroidal inhibition of circulating GH concentrations in thyroidectomized birds. Administration of IOP alone had no effect on GH concentrations. Circulating T3 concentrations were not enhanced following the administration of T4 to IOP-treated birds, indicating its inhibition of hepatic monodeiodinase activity. The metabolic clearance rate (MCR) of 125I-labelled chicken GH in the plasma of thyroidectomized fowl was less than that in sham-thyroidectomized birds. Following pretreatment with T4 (100 μg/kg per day for 7 days) sham-thyroidectomized and thyroidectomized birds did not differ significantly in their MCR. The GH secretion rate in thyroidectomized birds was similar to that in sham-thyroidectomized birds and in both groups was markedly reduced following pretreatment with T4. These results demonstrate thyroidal inhibition of circulating GH concentrations in fowl. Both T3 and T4 inhibited GH concentrations and the effect of T4 was not simply due to its role as a T3 prohormone. In the absence of thyroid hormones, the MCR of GH was reduced but its secretion rate was not enhanced. A significant reduction of GH secretion rate occurs in response to exogenous T4, in the absence of any change in GH metabolism. Journal of Endocrinology (1990) 124, 215–223


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