Effect of prostaglandin inhibition by indomethacin on plasma active and inactive renin concentration in men

1991 ◽  
Vol 69 (9) ◽  
pp. 1355-1359 ◽  
Author(s):  
P. Lijnen ◽  
J. Staessen ◽  
R. Fagard ◽  
A. Amery

The effect of inhibition of prostaglandin synthesis by indomethacin on active renin and on acid-activable inactive renin was studied in nine healthy, sodium-replete men, both at rest and exercise. These volunteers were investigated after pretreatment with placebo or indomethacin, 150 mg daily for 3 days. Indomethacin induced a decrease in active (p = 0.004), total (p < 0.001), and inactive (p = 0.02) renin at rest recumbent on average by 42, 19, and 8%, respectively, and at rest sitting on average by 45, 15, and 3%, respectively. Inhibition of prostaglandins with indomethacin reduced (p < 0.001) active and total renin at each level of work load but not (p = 0.32) inactive renin. However, the exercise-induced stimulation (p < 0.05) of active and total renin still occur during indomethacin. Indomethacin reduced (p < 0.001) at rest sitting and at maximal exercise the plasma concentrations of immunoreactive prostaglandins E2 by 50 and 54%, respectively, prostaglandin F2α by 36 and 39%, respectively, and 13,14-dihydro-15-keto-prostaglandin Fα by 38 and 60%, respectively. The urinary excretion of immunoreactive prostaglandin E2 and F2α was also reduced.Key words: indomethacin, prorenin, active renin, prostaglandins.

1978 ◽  
Vol 55 (s4) ◽  
pp. 155s-157s ◽  
Author(s):  
K. W. Rumpf ◽  
B. Schächterle ◽  
S. Schmidt ◽  
K. Becker ◽  
F. Scheler

1. The response of active and inactive plasma renin to orthostasis and frusemide and to inhibition of prostaglandin synthesis by indomethacin was tested in normal human volunteers. 2. Active renin increased by orthostasis and frusemide and decreased by indomethacin. The latter also blunted the increase of active renin after stimuli. 3. Inactive renin was slightly increased by orthostasis, but was not significantly influenced by acute administration of frusemide or inhibition of prostaglandin synthesis by indomethacin. 4. The results show differences in the response of active and inactive renin to stimuli and suppression. Opposite changes of active and inactive renin were not observed in the experimental conditions studied.


1993 ◽  
Vol 84 (1) ◽  
pp. 21-29 ◽  
Author(s):  
Kazuo Takaori ◽  
Shokei Kim ◽  
Akiyoshi Fukamizu ◽  
Masashi Sagara ◽  
Masayuki Hosoi ◽  
...  

1. Biochemical properties of human renin expressed in transgenic mice (hRN8-12 mice) carrying the human renin gene (Fukamizu et al. Biochem Biophys Res Commun 1989; 165: 826–32) were examined. The optimum pH of the enzymic activity against human angiotensinogen was 5.5 for both plasma and renal human renin in the hRN8-12 mice. Plasma concentrations of human active and inactive renin in the plasma of hRN8-12 mice were 16.7 ± 2.8 and 79.9 ± 14.0 pmol of angiotensin 1 h−1 ml−1, respectively, thereby indicating that the predominant form of plasma human renin is the inactive form, as is the case in humans. 2. The molecular masses of plasma human active and inactive renin and renal human active renin in the hRN8-12 mice were estimated to be 46kDa, 48kDa and 44kDa, respectively, as determined by h.p.l.c. on G3,000SW. 3. Human renin in the hRN8-12 mouse kidney was bound to a concanavalin A-Sepharose column, and was eluted with α-methyl-d-mannoside, showing that this renin is glycosylated, as is native human renin. 4. Low sodium treatment of the hRN8-12 mice for 2 weeks increased plasma human active renin, renal human renin and renal human renin mRNA levels by 2.6-, 3.8- and 2.8-fold, respectively. Thus, the biosynthesis and secretion of renal human renin in these transgenic mice are obviously stimulated by sodium depletion.


1989 ◽  
Vol 257 (4) ◽  
pp. R765-R770 ◽  
Author(s):  
K. T. Nakamura ◽  
J. M. Klinkefus ◽  
F. G. Smith ◽  
T. Sato ◽  
J. E. Robillard

The role of renal nerves and norepinephrine release on renin secretion during fetal and postnatal maturation has not been studied. Experiments were performed to determine the effect of veratridine, a substance known to promote norepinephrine release from nerve terminals, on active and inactive renin secretion from renal cortical slices of fetal (134-138 days gestation; term is 145 days), newborn (4-9 days of age), and adult nonpregnant sheep. Veratridine (10-300 microM) significantly increased active renin secretion and produced a small but nonsignificant rise in inactive renin secretion in all three groups of animals (P less than 0.05). The percent rise in active renin secretion during veratridine stimulation was similar among all groups. Veratridine-stimulated (300 microM) active renin secretion was antagonized by tetrodotoxin (0.5 and 5.0 microM) and DL-propranolol (1 microM) in fetal renal cortical slices. However, neither tetrodotoxin nor propranolol completely inhibited the stimulatory effect of veratridine on active renin secretion. These results suggest that 1) norepinephrine released from nerve terminals may regulate active renin secretion early during development; 2) the effect of veratridine on active renin secretion was similar in fetal, newborn, and adult sheep; 3) veratridine had no significant effect on inactive renin secretion; and 4) active renin secretion due to depolarization of nerve terminals in fetal sheep is dependent on activation of beta-adrenoceptors as it is in adults.


1984 ◽  
Vol 4 (1) ◽  
pp. 107-109 ◽  
Author(s):  
E. Shohami ◽  
A. Sidi

The effect of haemorrhagic hypotension on the levels of prostaglandin E2 (PGE2), thromboxane B2 (TXB2), and 6-keto prostaglandin F1α (6-keto-PGF1α) in cortical tissue of rats was studied. Lightly anesthetized rats were subjected to steady-state hypotension for 15 min, with a mean arterial blood pressure of 80, 60, and 40 mm Hg, and compared to a control group of normotensive rats. No significant change was found in the levels of PGE2 and TXB2. The level of 6-keto-PGF1α increased from 7.8 ± 0.9 to 14.1 ± 1.9 pg/mg protein (p < 0.02) at 80 mm Hg. Our findings suggest that prostacyclin, which is a potent vasodilator, might play a role in setting the lower limit of the autoregulation range.


Cephalalgia ◽  
2011 ◽  
Vol 31 (15) ◽  
pp. 1532-1541 ◽  
Author(s):  
Maria Antonova ◽  
Troels Wienecke ◽  
Jes Olesen ◽  
Messoud Ashina

Background: During two decades of migraine provocation studies with naturally occurring signalling molecules, vasodilators such as prostaglandin E2, prostaglandin I2 (prostacyclin) and prostaglandin D2 were shown to be able to induce headache in man. To elucidate the role of inflammation and vasodilatation in the generation of headache, we investigated whether the pro-inflammatory and vasoconstricting prostanoid prostaglandin F2α (PGF2α) would cause headache in a human model of headache. Methods: Twelve healthy volunteers were randomly allocated to receive 3.5 µg/kg/min PGF2α or placebo over 20 min in a two-way crossover study. We recorded headache intensity on a verbal rating scale, middle cerebral artery blood flow velocity (VMCA) and the diameters of the superficial temporal artery (STA) and radial artery (RA). Results: We found no difference in the area under the curve (AUC) for immediate headache (0–90 min) between PGF2α and placebo ( p = 0.144). The McNemar's test showed no difference in the incidence of immediate and delayed headache between verum and placebo ( p = 0.500 and p = 1.000, respectively). There was no difference in VMCA ( p = 0.776) and in the diameter of the STA ( p = 0.460) or RA ( p = 0.780) between PGF2α and placebo. Conclusion: The present study shows that PGF2α, unlike vasodilating prostaglandins, does not provoke headache. We suggest that the vasodilating abilities of prostaglandins are important for the induction of experimental headache in healthy volunteers.


1986 ◽  
Vol 66 (3) ◽  
pp. 643-651 ◽  
Author(s):  
J. A. FITZGERALD ◽  
G. A. EVERETT ◽  
J. APGAR

The effect of low dietary Zn intake upon several plasma endocrine and metabolic profiles was examined during late gestation in the ewe. Thirty adult, primiparous Finncross ewes were fed a low Zn diet with (+Zn, n = 14) or without (0Zn, n = 16) supplemental Zn in the drinking water starting day 1 of pregnancy. Although the mean prepartum progesterone and prolactin concentrations were lower (P < 0.05 and P < 0.01, respectively) in 0Zn than in +Zn ewes, the peak prolactin concentrations in 0Zn ewes at lambing were similar to +Zn ewes. Both basal and thyrotropin-releasing-hormone (TRH)-induced prolactin release were less (P < 0.01) in 0Zn ewes 2 d postpartum. Plasma concentrations of 13, 14-dihydro-15-keto prostaglandin F2α (PGFM) of ewes sampled within 45 min post-lambing were lower (P < 0.05) in 0Zn ewes. There was no difference in cortisol concentrations within 45 min after lambing between 0Zn and + Zn ewes. Plasma protein concentrations in 0Zn ewes were higher (P < 0.01) than those in +Zn ewes during pregnancy. In summary, these data show that low Zn intake in the pregnant ewe affected several endocrine and metabolic plasma parameters associated with normal pregnancy and parturition. Key words: Zinc, parturition, dystocia, feed intake, ovine


1980 ◽  
Vol 48 (6) ◽  
pp. 999-1007 ◽  
Author(s):  
K. Kabayashi ◽  
S. M. Horvath ◽  
F. J. Diaz ◽  
D. R. Bransford ◽  
B. L. Drinkwater

The time course of whole-body sweating and thermal regulation during rest and exercise in a hot humid environment was investigated in three body postures. After 45 min rest in the upright, low-sit, or supine posture, five unacclimatized men exercised for 45 min on a bicycle ergometer in the same posture in an environment of 49.5 degrees C, 28.9 Torr. Exercise was performed at two different work loads, corresponding to about 30 and 45% of VO2max. During exercise auditory canal temperature, rectal temperature, and mean skin temperature increased linearly being highest in the supine and lowest in the upright posture. Percentage of evaporated sweat from the skin to secreted sweat was 65% in upright, 52% in the low-sit, and only 46% in the supine posture during the last 20 min of exercise regardless of work load. The time course of the rate of body heat storage was different from predictions based on the thermal balance equation. Evaporative heat loss was not 100% effective in cooling the skin surface.


1989 ◽  
Vol 17 (6) ◽  
pp. 506-513 ◽  
Author(s):  
A.T. Dinh Xuan ◽  
C. Lebeau ◽  
R. Roche ◽  
A. Ferriere ◽  
M. Chaussain

The effects of inhaled terbutaline, a β2-adrenergic agonist, administered via a 750-ml spacer device were studied in young asthmatic subjects with exercise-induced asthma. A double-blind, randomized, placebo-controlled study of the effects of inhaled 0.5 mg terbutaline and placebo was conducted in 10 asthmatic children (age range 6–16 years) with documented exercise-induced asthma. Forced expiratory volume in 1 s (FEV1) was measured at baseline, 15 min after inhaling terbutaline or placebo, and at intervals up to 60 min after exercising. Subjects exercised using a cycle ergometer for 5 min at a submaximal, constant work-load while breathing dry air at room temperature. Terbutaline induced bronchodilation at rest in all subject and fully prevented exercise-induced asthma in nine out of the 10 subjects; the exercise-induced fall in FEV1 was markedly reduced in the remaining subject. It is concluded that exercise-induced asthma can be inhibited by pretreatment with inhaled terbutaline, administered via a spacer, in a majority of young asthmatics.


Pharmacology ◽  
2021 ◽  
pp. 1-8
Author(s):  
Alex Guazzi Rodrigues ◽  
Helton Oliveira Campos ◽  
Lucas Rios Drummond ◽  
Umeko Marubayashi ◽  
Cândido Celso Coimbra

<b><i>Aim:</i></b> The aim of this study was to assess the influence of adrenomedullary secretion on the plasma glucose, lactate, and free fatty acids (FFAs) during running exercise in rats submitted to intracerebroventricular (i.c.v.) injection of physostigmine (PHY). PHY i.c.v. was used to activate the central cholinergic system. <b><i>Methods:</i></b> Wistar rats were divided into sham-saline (sham-SAL), sham-PHY, adrenal medullectomy-SAL, and ADM-PHY groups. The plasma concentrations of glucose, lactate, and FFAs were determined immediately before and after i.c.v. injection of 20 μL of SAL or PHY at rest and during running exercise on a treadmill. <b><i>Results:</i></b> The i.c.v. injection of PHY at rest increased plasma glucose in the sham group, but not in the ADM group. An increase in plasma glucose, lactate, and FFAs mobilization from adipose tissue was observed during physical exercise in the sham-SAL group; however, the increase in plasma glucose was greater with i.c.v. PHY. Moreover, the hyperglycemia induced by exercise and PHY in the ADM group were blunted by ADM, whereas FFA mobilization was unaffected. <b><i>Conclusion:</i></b> These results indicate that there is a dual metabolic control by which activation of the central cholinergic pathway increases plasma glucose but not FFA during rest and exercise, and that this hyperglycemic response is dependent on adrenomedullary secretion.


2012 ◽  
Vol 8 (3-4) ◽  
pp. 213-218 ◽  
Author(s):  
D. Serteyn ◽  
I. Caudron ◽  
J.-P. Lejeune ◽  
D. Votion ◽  
J. Ceusters ◽  
...  

Endurance race induces a rise of serum creatine kinase (CK) activity and a systemic inflammatory like response characterised by an increase of neutrophil counts, plasma and muscle myeloperoxidase (MPO) and elastase (ELT) concentrations in horses. Horses performing the same standardised exercise test do not respond with the same magnitude of inflammatory reaction. The aim of the present study was to measure the total neutrophil count, the ratio neutrophil:lymphocyte, the MPO and ELT plasma concentrations and concomitant increases of serum CK activities in competing endurance horse and to relate these results to their race performance. Twenty one horses participating in a 120 km 4 star endurance race recruited on a voluntary basis finished the race with a mean speed ranging from 13.1 to 19.8 km/h. Blood was taken the day before the race and two hours after the race. Mean values of neutrophil counts, ratio neutrophil:lymphocyte, plasma MPO and ELT concentrations and serum CK activities after the race were significantly higher than the pre-race values. There was no correlation between neutrophil counts, MPO, ELT or CK and the mean speed of the horses during the race except for the ratio neutrophil:lymphocyte where a significant negative correlation was observed. These results showed that systemic responses induced by strenuous exercise such as an endurance race is not clearly related to performance but also to horse-related factors, such as intrinsic capacity or training.


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