Investigation of human and rat inactive renin in plasma and kidney

1991 ◽  
Vol 69 (9) ◽  
pp. 1341-1349 ◽  
Author(s):  
A. Jindra Jr. ◽  
J. Bultas ◽  
J. Ort ◽  
R. Kvetnansky
Keyword(s):  
Immobilization Stress ◽  
Rat Kidney ◽  
Total Activity ◽  
Renin Secretion ◽  
Renal Veins ◽  
Bicycle Exercise ◽  
Initial Interval ◽  
Active Renin ◽  
Inactive Renin

Under an initial interval of immobilization stress in rats, reciprocal changes of plasma active and inactive renin were observed, suggesting activation of circulating inactive renin. Molecular weight (MW) studies revealed that this activation might proceed via a MW shift from inactive renin with MW of 50 000 to active renin of MW 43 000. In a later interval of stress, under stimulated renin secretion, a lower MW form (38 000) of active renin was released into the circulation. This MW is close to that of active renin (39 000) found in rat kidney renin granules. In renin granules, equilibrated in fractions of 1.6 and 1.7 mol/L sucrose in discontinuous density gradient, trypsin-activatable renin activity formed 36 and 16% of total activity, respectively. In humans, under acute bicycle exercise, a lower MW form (39 000) of active renin was released into the circulation, while the content of inactive renin with MW in the range of 51 000–58 000 and at 47 000 did not substantially change. There was a slight decrease in circulating inactive renin passing through the kidney. The data suggest that, at least in rats, in vivo pathways for activation of inactive renin might exist, other than that proceeding before secretion from renin granules. Under the conditions of increased renin secretion, a lower MW form of active renin is mainly released into the circulation in both rats and humans.Key words: active renin, inactive renin, renal veins, renin granules, stress.

Ontogeny of neuronally released norepinephrine on renin secretion in sheep

1989 ◽  
Vol 257 (4) ◽  
pp. R765-R770 ◽  
Author(s):  
K. T. Nakamura ◽  
J. M. Klinkefus ◽  
F. G. Smith ◽  
T. Sato ◽  
J. E. Robillard
Keyword(s):  
Renin Secretion ◽  
Renal Nerves ◽  
Nerve Terminals ◽  
Norepinephrine Release ◽  
Fetal Sheep ◽  
Postnatal Maturation ◽  
Active Renin ◽  
Inactive Renin ◽  
Cortical Slices

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.

Regulation of glycogenolysis in human muscle at rest and during exercise

1982 ◽  
Vol 53 (3) ◽  
pp. 708-715 ◽  
Author(s):  
D. Chasiotis ◽  
K. Sahlin ◽  
E. Hultman
Keyword(s):  
Glycogen Phosphorylase ◽  
Total Activity ◽  
Human Muscle ◽  
Phosphorylase Activity ◽  
Michaelis Constant ◽  
Bicycle Exercise ◽  
Muscle Phosphorylase ◽  
Glycogen Utilization ◽  
Main Factors

The regulation of glycogenolysis in human muscle during isometric and dynamic exercise has been investigated. Total glycogen phosphorylase and synthase activities were unchanged during exercise. The fraction of phosphorylase in the alpha form at rest was estimated to be 20%, but the data indicate that the in vivo activity was low and critically dependent on the concentration of inorganic phosphate (Pi) in the muscle. Phosphorylase alpha increased initially 2.4-fold during isometric contraction and 1.6-fold during maximal bicycle exercise but reverted to or below the resting value at fatigue/exhaustion. At rest synthase I was 1713;48% of the total activity but decreased during exercise to about half of this value. The reciprocal changes in phosphorylase and synthase correlate with the enhanced rate of glycogenolysis during exercise. Michaelis constant (Km) for Pi was 27 mmol . l-1 for phosphorylase alpha and 7 mmol . l-1 for alpha + b. From consideration of the changes in Pi during exercise (to 20–30 mmol . l–1) it was concluded that Pi is one of the main factors determining phosphorylase activity and provides a link between phosphocreatine breakdown and glycogen utilization in muscle.

Regulation of in vitro renin secretion by ANG II feedback manipulation in vivo in the ovine fetus

1999 ◽  
Vol 277 (4) ◽  
pp. R1230-R1238 ◽  
Author(s):  
Carlos E. Giammattei ◽  
Jack W. Strandhoy ◽  
James C. Rose
Keyword(s):  
Feedback Regulation ◽  
Late Gestation ◽  
Renin Secretion ◽  
Juxtaglomerular Cells ◽  
Fetal Life ◽  
Ang Ii ◽  
Active Renin ◽  
Age Related

The renin-angiotensin system is critically important to fetal cardiovascular function and organ development. The feedback regulation of renin secretion by ANG II develops early in gestation yet does not linearly progress from fetal life to adulthood. Renin secretion is elevated in late gestation compared with earlier or postnatal time periods, which suggests that some component of the negative feedback regulation of renin secretion is less sensitive in late gestation. We examined in fetal sheep the age-related consequence of chronic in vivo manipulation of ANG II on renal renin secretion measured in vitro. Immature (101–103 days of gestation) and mature (130–133 days of gestation) fetuses were treated for 72 h with enalaprilat, ANG II or vehicle. Content and basal and isoproterenol-stimulated secretion of prorenin (PR) and active renin (AR) from fetal kidney cortical slices were determined. Enalaprilat pretreatment in vivo increased renal renin content and basal and stimulated secretion of PR and AR in vitro even in immature animals. Immunohistochemical localization showed that enalaprilat treatment caused an age-related recruitment of renin-containing juxtaglomerular cells. Conversely, ANG II pretreatment decreased basal and stimulated PR and AR secretion from immature fetal kidneys, but only inhibited PR secretion from mature kidneys. It also caused an age-related decrease in the percentage of renin-containing juxtaglomerular cells. These results suggest that ANG II feedback modulates not only the synthesis and content of renin, but the sensitivity of the coupling between stimulus and secretion. A critical observation of our study is that the higher renal tissue concentrations of prorenin and active renin in late gestation may be a consequence of reduced sensitivity to ANG II feedback; this is consistent with the increased plasma concentrations of renin found in near-term mammals.

Active and inactive renin in human forearm of hypertensive patients

1991 ◽  
Vol 69 (9) ◽  
pp. 1390-1393 ◽  
Author(s):  
Stefano Taddei ◽  
Stefania Favilla ◽  
Antonio Salvetti
Keyword(s):  
Brachial Artery ◽  
Vascular Tissue ◽  
Physiological Role ◽  
Renin Angiotensin System ◽  
Hypertensive Patients ◽  
Active Renin ◽  
Inactive Renin ◽  
Dose Dependent

Although many in vitro and animal studies indicate the existence of a local renin–angiotensin system, data regarding its physiological role are quite controversial, and moreover, evidence suggesting inactive and active renin release from vascular tissue in vivo is lacking both in animal and humans. The aim of our study was to evaluate whether β-adrenoceptor stimulation, a well-known stimulus to renin production, through isoproterenol might cause local renin production from vessels of the forearm of hypertensive patients. Drugs were infused into the brachial artery at systemically ineffective rates, while forearm blood flow (FBF, venous plethysmography), mean intra-arterial pressure, and heart rate were monitored throughout. Active and inactive vessel renin production was measured by calculating venous-arterial (V-A) differences by simultaneous sampling from brachial artery and an ipsilateral deep vein. Active renin (PRA) and total renin (Sepharose bound trypsin activation) were measured by radioimmunoassay while inactive renin was calculated as the difference between total and active renin. V-A differences were corrected for FBF to calculate renin extraction or production. In a group of 10 patients, isoproterenol, which was infused at increasing cumulative rates (0.03, 0.1, 0.3 μg∙100 mL−1 forearm tissue∙min−1 for 5 min each), caused a dose-dependent increment in FBF that was blunted by intra-arterial propranolol (n = 5) pretreatment (10 μg∙100 mL−1 forearm tissue∙min−1 for 10 min). β-Adrenoceptor stimulation caused a dose-dependent outflow of both active and inactive renin, an effect antagonized by propranolol. In conclusion, our data represent the first evidence in humans of tissue active and inactive renin production in the forearm vascular bed.Key words: tissue renin, active renin, inactive renin, isoproterenol.

Generation of Inactive Renin in Vitro and in Vivo: Reversible Inactivation of the Active Plasma Enzyme in Rats

1982 ◽  
Vol 63 (s8) ◽  
pp. 171s-174s ◽  
Author(s):  
Jack D. Barrett ◽  
Peter Eggena ◽  
Mohinder P. Sambhi
Keyword(s):  
Active Form ◽  
Renin Angiotensin System ◽  
Active Plasma ◽  
Reversible Inactivation ◽  
Active Renin ◽  
Plasma Enzyme ◽  
Inactive Renin ◽  
Rate Of Decline

1. Active and total (trypsin treatment) plasma renins were measured in normal Wistar rats and in rats in which the renin-angiotensin system was stimulated by ether anaesthesia. 2. After incubation of normal plasma in vitro in the absence of angiotensinase inhibitors, active renin declined. This decline was shown to be due to the conversion of active renin into an inactive form, which could be re-activated by trypsin. 3. In plasma from renin-stimulated rats, the rate of decline of active renin in vitro was accelerated; however, the relative amount of inactive renin generated was decreased. 4. Ligation of the kidneys of the ether-anaesthetized animal resulted in a build-up in vivo of inactive renin concomitant with the decline of active renin. 5. These data demonstrate the conversion of active into inactive renin in vitro and indicate that inactive renin can also be generated in vivo from the active form of the enzyme. 6. Multiple forms of inactive renin may exist; some may be true ‘prorenins’ (renin zymogens) produced in the kidney, and others may result from post-biosynthetic modifications of the active plasma enzyme.

Ontogeny of isoproterenol-stimulated renin secretion from sheep renal cortical slices

1989 ◽  
Vol 256 (6) ◽  
pp. R1258-R1263
Author(s):  
K. T. Nakamura ◽  
W. V. Page ◽  
T. Sato ◽  
J. M. Klinkefus ◽  
J. E. Robillard
Keyword(s):  
Active Form ◽  
Age Groups ◽  
The Other ◽  
Renin Secretion ◽  
Base Line ◽  
Active Renin ◽  
Kidney Slices ◽  
Inactive Renin ◽  
Synthase Inhibitor ◽  
Cortical Slices

The ontogeny of renin secretion from renal cortical slices was studied in two groups of fetal (107-109 days of gestation and 131-136 days of gestation; term is 145 days), newborn (3-9 days old), and adult nonpregnant sheep. Isoproterenol (ISO; 10(-8)-10(-5) M) significantly increased active renin secretion in all age groups (P less than 0.05), with newborns having the highest values at all concentrations. However, the percent changes in active renin secretion were similar among all ages. Inactive renin secretion also increased with ISO stimulation, with newborns having the highest rate of inactive renin secretion. The percent of total renin in the active form differed among ages, ranging at base line from 60 +/- 10% in fetuses at greater than 130 days of gestation to 88 +/- 6% in fetuses at less than 110 days of gestation (P less than 0.05). Propranolol (1 microM) inhibited ISO (10(-6) M)-stimulated active renin secretion at all ages. On the other hand, the prostaglandin (PG) synthase inhibitor aspirin (1.6 x 10(-5) M) did not inhibit ISO (10(-6) M)-mediated increases in active renin secretion in fetal (greater than 130 days of gestation) kidney slices and produced values intermediate between base line and ISO alone in newborns and adults.(ABSTRACT TRUNCATED AT 250 WORDS)

Release of Active and Inactive Renin by the Human Kidney

1979 ◽  
Vol 57 (s5) ◽  
pp. 101s-103s ◽  
Author(s):  
W. Aoi ◽  
S. Seto ◽  
Y. Doi ◽  
M. Murayama ◽  
S. Tasaki ◽  
...  
Keyword(s):  
Inferior Vena Cava ◽  
Inferior Vena ◽  
Vena Cava ◽  
Human Kidney ◽  
Upright Position ◽  
Renal Veins ◽  
Active Renin ◽  
Affected Side ◽  
Inactive Renin ◽  
Renal Abnormalities

1. Active and inactive renin were assayed in plasma of the renal veins and the inferior vena cava below the kidney in eight patients with hypertension and unilateral renal abnormalities, 20 min after the patients had resumed the upright position. 2. The concentration of active renin on the affected side was significantly higher than that on the non-affected side. The concentration of inactive renin on the affected side was significantly lower than that on the non-affected side and in the inferior vena cava. 3. These findings suggest either that the affected kidney mainly secretes active renin, which is then converted into inactive renin in the extrarenal circulation, or that the affected kidney activates inactive renin.

The Fine Structure of Rat Renal Microbodies and Cytoplasmic Bodies Following Perfusion Fixation

1973 ◽  
Vol 31 ◽  
pp. 620-621
Author(s):  
J. M. Barrett ◽  
P. M. Heidger
Keyword(s):  
Fine Structure ◽  
Proximal Tubule ◽  
Rat Kidney ◽  
Renal Proximal Tubule ◽  
Convincing Evidence ◽  
Cytoplasmic Bodies ◽  
Rat Renal Proximal Tubule ◽  
Renal Proximal Tubule Cells ◽  
Perfusion Fixation

Microbodies have received extensive morphological and cytochemical investigation since they were first described by Rhodin in 1954. To our knowledge, however, all investigations of microbodies and cytoplasmic bodies of rat renal proximal tubule cells have employed immersion fixation. Tisher, et al. have shown convincing evidence of fine structural alteration of microbodies in rhesus monkey kidney following immersion fixation; these alterations were not encountered when in vivo intravascular perfusion was employed. In view of these studies, and the fact that techniques for perfusion fixation have been established specifically for the rat kidney by Maunsbach, it seemed desirable to employ perfusion fixation to study the fine structure and distribution of microbodies and cytoplasmic bodies within the rat renal proximal tubule.

scholarly journals Development of 18F-Labeled Radiotracers for PET Imaging of the Adenosine A2A Receptor: Synthesis, Radiolabeling and Preliminary Biological Evaluation

2021 ◽  
Vol 22 (5) ◽  
pp. 2285
Author(s):  
Thu Hang Lai ◽  
Susann Schröder ◽  
Magali Toussaint ◽  
Sladjana Dukić-Stefanović ◽  
Mathias Kranz ◽  
...  
Keyword(s):  
Specific Binding ◽  
Brain Slices ◽  
Total Activity ◽  
Biological Evaluation ◽  
Adenosine A2a Receptor ◽  
Positron Emission ◽  
A2a Receptor ◽  
Adenosine A2a

The adenosine A2A receptor (A2AR) represents a potential therapeutic target for neurodegenerative diseases. Aiming at the development of a positron emission tomography (PET) radiotracer to monitor changes of receptor density and/or occupancy during the A2AR-tailored therapy, we designed a library of fluorinated analogs based on a recently published lead compound (PPY). Among those, the highly affine 4-fluorobenzyl derivate (PPY1; Ki(hA2AR) = 5.3 nM) and the 2-fluorobenzyl derivate (PPY2; Ki(hA2AR) = 2.1 nM) were chosen for 18F-labeling via an alcohol-enhanced copper-mediated procedure starting from the corresponding boronic acid pinacol ester precursors. Investigations of the metabolic stability of [18F]PPY1 and [18F]PPY2 in CD-1 mice by radio-HPLC analysis revealed parent fractions of more than 76% of total activity in the brain. Specific binding of [18F]PPY2 on mice brain slices was demonstrated by in vitro autoradiography. In vivo PET/magnetic resonance imaging (MRI) studies in CD-1 mice revealed a reasonable high initial brain uptake for both radiotracers, followed by a fast clearance.

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