Effect of tolbutamide on plasma renin activity.

1979 ◽  
Vol 236 (1) ◽  
pp. E1
Author(s):  
N K Sherma ◽  
V V Gossain ◽  
A M Michelakis ◽  
D R Rovner
Keyword(s):  
Cyclic Amp ◽  
Plasma Renin Activity ◽  
Biological Significance ◽  
Plasma Renin ◽  
Renin Activity ◽  
Control Group ◽  
Cortical Slices ◽  
Intact Rats

The effect of tolbutamide on renin secretion in rats was studied in vivo, and in vitro. Administration of tolbutamide in doses of 12.5 and 25 mg/kg body wt ip to two groups of rats produced no significant change in plasma renin activity compared to the control group. In the in vitro experiments renal cortical slices were incubated with increasing concentrations of tolbutamide (0--4 mg/ml). No significant increase in the net renin production was observed, whereas the concentration of cyclic AMP increased significantly in the incubation medium. These findings suggest that in the intact rats tolbutamide does not increase plasma renin activity. In the renal cortical experiments although tolbutamide increased cyclic AMP production, the increase may not have been sufficient to stimulate the net renin production. These results are of biological significance because of the possible effects of tolbutamide and increased plasma renin activity on the cardiovascular system.

Effects of Stimulation and Inhibition of the Renal Prostaglandin Synthetase System on Renin Release in vivo and in vitro

1976 ◽  
Vol 51 (s3) ◽  
pp. 271s-274s
Author(s):  
P. C. Weber ◽  
C. Larsson ◽  
M. Hamberg ◽  
E. Änggård ◽  
E. J. Corey ◽  
...  
Keyword(s):  
Plasma Renin Activity ◽  
Plasma Renin ◽  
Renin Activity ◽  
Renin Release ◽  
Rabbit Kidney ◽  
Kidney Cortex ◽  
Acid Pretreatment ◽  
Prostaglandin Endoperoxide

1. The prostaglandin precursor arachidonic acid (C20:4) increases plasma renin activity in the rabbit and rat when it is infused into the renal arteries. 2. The increase in plasma renin activity after C20:4 in rats is not changed by volume expansion. 3. The inhibitor of prostaglandin synthesis indomethacin decreases plasma renin activity in the rabbit. 4. The increase in plasma renin activity after total renal ischaemia is abolished by pretreatment with indomethacin. 5. C20:4 increases dose- and time-dependent renin release from slices of rabbit kidney cortex. 6. Indomethacin or 5,8,11,14-eicosatetraynoic acid pretreatment in vivo, and addition to the incubation medium, reduces basal as well as C20:4-stimulated renin release in vitro. 7. The stimulating effect of C20:4 on renin release is assumed to be caused directly by formation of prostaglandin endoperoxides in the kidney cortex and not by prostaglandins since in vitro a natural prostaglandin endoperoxide (PGG2) and two stable synthetic prostaglandin endoperoxide analogues (EPA I and EPA II) do increase the release of renin, but PGE2 has no effect and PGF2α inhibits renin release.

Effects of Angiotensinase Inhibitors on Plasma Protein Binding and IC50 Determinations of Renin Inhibitors

1992 ◽  
Vol 38 (11) ◽  
pp. 2239-2243 ◽  
Author(s):  
B D Dayton ◽  
H H Stein ◽  
J Cohen ◽  
W R Baker ◽  
S A Boyd ◽  
...  
Keyword(s):  
Plasma Renin Activity ◽  
Plasma Proteins ◽  
Proteinase Inhibitors ◽  
Plasma Renin ◽  
Renin Activity ◽  
Phenylmethylsulfonyl Fluoride ◽  
Renin Inhibitors ◽  
Ic50 Values

Abstract To establish whether the use of proteinase inhibitors in the routine determination of in vitro plasma renin activity overestimates the potency of renin inhibitors in vivo, we examined the effects of phenylmethylsulfonyl fluoride and 8-hydroxyquinoline sulfate on the binding to plasma proteins and the respective IC50 values (50% inhibiting concentrations) of three renin inhibitors. All three renin inhibitors, A-64662, A-65317, and A-74273, bound (> 60%) to plasma proteins at both pH 6.0 and 7.4, with slightly greater binding at pH 7.4. Phenylmethylsulfonyl fluoride (1.45 mmol/L) had no significant effect on the protein binding at either pH 6.0 or 7.4; 8-hydroxyquinoline sulfate (3.4 mmol/L) caused a modest dissociation (10-30%) of the renin inhibitors from plasma proteins at both pH values; and the effects of both proteinase inhibitors together were similar to those of 8-hydroxyquinoline alone. At pH 7.4, phenylmethylsulfonyl fluoride increased the potencies of the three renin inhibitors slightly (< or = 43%), whereas IC50 values determined in the presence of 8-hydroxyquinoline decreased by 1.5- to 3.7-fold. The greatest increase in potency occurred with the most hydrophilic compound, and with both angiotensinase inhibitors the effect was no greater than that of 8-hydroxyquinoline alone. The results show that any dissociation of the hypotensive activity measured in vivo from the plasma renin activity measured in vitro is not simply an artifact in the plasma renin activity assay stemming from the use of these angiotensinase inhibitors, especially if only phenylmethylsulfonyl fluoride is used.

Control of Renin Secretion in Vivo and in Vitro in Rats: Arguments in Favour of a Precursor Form of Renin and of a Role of a Microtubular System

1976 ◽  
Vol 51 (s3) ◽  
pp. 93s-95s ◽  
Author(s):  
F. Banichahi ◽  
A. Capponi ◽  
C. Pricam ◽  
C. De Senarclens ◽  
M. B. Vallotton
Keyword(s):  
Endoplasmic Reticulum ◽  
Plasma Renin Activity ◽  
Plasma Renin ◽  
Juxtaglomerular Apparatus ◽  
Granular Endoplasmic Reticulum ◽  
Renin Activity ◽  
Renin Substrate ◽  
Salt Depletion

1. The morphology of the juxtaglomerular apparatus, plasma renin activity, plasma renin substrate and renal renin have been studied in rats after maximal stimulation by bilateral adrenalectomy and salt depletion, and also after blocking this stimulation by deoxycorticosterone and salt load. 2. After stimulation the juxtaglomerular apparatus showed a well-developed granular endoplasmic reticulum and a low secretory granule content. Plasma renin activity was markedly elevated and plasma renin substrate was low. After blockade numerous specific granules with crystalline structures were seen and the granular endoplasmic reticulum was less developed. Plasma renin activity was now low and plasma renin substrate elevated. 3. After prior acidification of the kidney extract a significant increase of renal renin was observed in both conditions but was greater in the second group at the time when large numbers of young granules containing crystalline material were seen. 4. Kidney slices from the adrenalectomized salt-depleted rats released more renin than control slices. Vincristine did not affect this release, but inhibited release from slices stimulated by isoprenaline.

scholarly journals A fluorogenic near-infrared imaging agent for quantifying plasma and local tissue renin activity in vivo and ex vivo

2012 ◽  
Vol 303 (4) ◽  
pp. F593-F603 ◽  
Author(s):  
Jun Zhang ◽  
Dorin V. Preda ◽  
Kristine O. Vasquez ◽  
Jeff Morin ◽  
Jeannine Delaney ◽  
...  
Keyword(s):  
Plasma Renin Activity ◽  
Near Infrared ◽  
Ex Vivo ◽  
Kidney Tissue ◽  
Plasma Renin ◽  
Renin Activity ◽  
Imaging Agent ◽  
Ang Ii

The renin-angiotensin system (RAS) is well studied for its regulation of blood pressure and fluid homeostasis, as well as for increased activity associated with a variety of diseases and conditions, including cardiovascular disease, diabetes, and kidney disease. The enzyme renin cleaves angiotensinogen to form angiotensin I (ANG I), which is further cleaved by angiotensin-converting enzyme to produce ANG II. Although ANG II is the main effector molecule of the RAS, renin is the rate-limiting enzyme, thus playing a pivotal role in regulating RAS activity in hypertension and organ injury processes. Our objective was to develop a near-infrared fluorescent (NIRF) renin-imaging agent for noninvasive in vivo detection of renin activity as a measure of tissue RAS and in vitro plasma renin activity. We synthesized a renin-activatable agent, ReninSense 680 FAST (ReninSense), using a NIRF-quenched substrate derived from angiotensinogen that is cleaved specifically by purified mouse and rat renin enzymes to generate a fluorescent signal. This agent was assessed in vitro, in vivo, and ex vivo to detect and quantify increases in plasma and kidney renin activity in sodium-sensitive inbred C57BL/6 mice maintained on a low dietary sodium and diuretic regimen. Noninvasive in vivo fluorescence molecular tomographic imaging of the ReninSense signal in the kidney detected increased renin activity in the kidneys of hyperreninemic C57BL/6 mice. The agent also effectively detected renin activity in ex vivo kidneys, kidney tissue sections, and plasma samples. This approach could provide a new tool for assessing disorders linked to altered tissue and plasma renin activity and to monitor the efficacy of therapeutic treatments.

Measurement of Plasma Renin Activity as a Valid Estimation of Plasma Angiotensin Status

1978 ◽  
Vol 15 (1-6) ◽  
pp. 250-252 ◽  
Author(s):  
J. E. Roulston ◽  
G. A. Macgregor ◽  
Theresa Adam ◽  
Nirmala D. Markandu
Keyword(s):  
Angiotensin Ii ◽  
Plasma Renin Activity ◽  
Plasma Renin ◽  
Renin Activity ◽  
Activity Measurement ◽  
Plasma Samples ◽  
Angiotensin I ◽  
Plasma Angiotensin ◽  
Rate Limiting

Measurement of plasma renin activity is widely used as an indirect assessment of plasma angiotensin II concentration. There has been some controversy over the validity of this assay as an estimate of circulating angiotensin II levels because, during the in vitro generation of angiotensin I by renin, over a period of time, substrate concentration may diminish to such an extent that it becomes rate-limiting, giving an artificially low reflection of angiotensin II levels. In this paper the initial angiotensin I concentration, that is the concentration before in vitro angiotensin I generation, has been compared with the corresponding plasma renin activity for 2752 individual plasma samples. A linear relationship was found between the initial angiotensin I concentration and the plasma renin activity below 60 ng ml−1 h−1. This indicates that, under the conditions of this assay, substrate does not appear to become rate-limiting except at exceedingly high levels of plasma renin activity. These results appear to provide further validation for the use of plasma renin activity measurement as a reflection of the concentration of circulating angiotensin II levels.

Glyburide attenuates calmodulin antagonist-stimulated renin release from isolated mouse juxtaglomerular cells

1995 ◽  
Vol 269 (2) ◽  
pp. F242-F247 ◽  
Author(s):  
D. A. Linseman ◽  
J. A. Lawson ◽  
D. A. Jones ◽  
J. H. Ludens
Keyword(s):  
Calcium Release ◽  
Plasma Renin ◽  
Renin Activity ◽  
Renin Release ◽  
K Channel ◽  
Inhibitory Effects ◽  
Calmodulin Antagonist ◽  
Voltage Gated Calcium Channels

Previous reports have shown that K+ channel openers elevate plasma renin activity in vivo and stimulate renin release (RR) from juxtaglomerular (JG) cells in vitro. Therefore, we examined whether the K+ channel blocker, glyburide, inhibits basal RR or RR stimulated by elevating cAMP or by inhibiting Ca2+/calmodulin activity in cultures of isolated mouse JG cells. Glyburide treatment (10-300 microM) had no effect on basal RR, which measured approximately 10% or 30% of the total cellular renin activity after 4 or 24 h, respectively. RR stimulated by elevating cAMP with isoproterenol, forskolin, or 3-isobutyl-1-methylxanthine was also unaffected by glyburide. In contrast, glyburide significantly attenuated RR stimulated by the calmodulin antagonists, calmidazolium, trifluoperazine, and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7). Calmidazolium-stimulated RR returned to basal levels with 100 microM glyburide cotreatment. Blockade of voltage-gated calcium channels with verapamil or inhibition of calcium release from intracellular stores with 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester (TMB-8) had no effect on the ability of glyburide to attenuate calmidazolium-stimulated RR. However, lowering of the extracellular calcium concentration by the addition of EGTA abolished the inhibitory effects of glyburide. We conclude that modulation of K+ channels may influence RR by affecting Ca2+/calmodulin-regulated secretion, but not cAMP-mediated secretion, from JG cells.(ABSTRACT TRUNCATED AT 250 WORDS)

BIOLOGICAL SIGNIFICANCE OF ACTIVE AND INACTIVE RENIN IN MAN

1980 ◽  
Vol 85 (1) ◽  
pp. 137-143 ◽  
Author(s):  
P. LIJNEN ◽  
A. AMERY ◽  
R. FAGARD ◽  
L. VERSCHUEREN
Keyword(s):  
Plasma Concentrations ◽  
Biological Significance ◽  
Plasma Renin ◽  
Angiotensin I ◽  
Vitro Assay ◽  
Arterial Blood ◽  
Inactive Renin ◽  
Change In Mean

SUMMARY The biological significance of active and inactive renin was investigated by comparison of an in-vitro assay of active, total and inactive plasma renin concentration (PRC), plasma renin activity (PRA) and plasma concentrations of angiotensin I and II with an in-vivo change in mean arterial blood pressure (MAP) produced by antagonism of angiotensin with treatment with saralasin and by blockade of angiotensin-converting enzyme by treatment with captopril. A significant relationship between the changes in MAP during treatment with saralasin and captopril with the pretreatment levels of PRA, active and total PRC and angiotensin II were found; while the pre-existing level of inactive renin was not a predictor for the hypotensive effect of saralasin and captopril. During treatment with saralasin and captopril significant increases in PRA, plasma angiotensin I concentration and total and active PRC were found and no change in inactive PRC was observed.

Photodynamic effects of Radachlorin® on cervical cancer model

2005 ◽  
Vol 09 (12) ◽  
pp. 835-840 ◽  
Author(s):  
Sun-Young Kwak ◽  
Dae-Seog Lim ◽  
Su-Mi Bae ◽  
Yong-Wook Kim ◽  
Joon-Mo Lee ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Golgi Apparatus ◽  
Biological Significance ◽  
Annexin V ◽  
Light Irradiation ◽  
Control Group ◽  
Cancer Model ◽  
In Vivo Experiments

Photodynamic therapy (PDT) has been reported to be effective for treating various tumors and induce apoptosis in many tumor cells. In this study, we examined a biological significance of PDT with a chlorin-based photosensitizer, Radachlorin®, in a cervical cancer model, TC-1 cells. When TC-1 cells were exposed to varied doses of Radachlorin® with light irradiation (6.25 J/cm2), PDT induced a dose-dependent growth inhibition of TC-1 cells. All of these cells were significantly damaged after light irradiation and categorized to be early and late apoptosis, as determined by annexin V staining. Radachlorin® localized primarily into the Golgi apparatus of cells in 12 h of the treatment, and weak fluorescence intensity was also detected in mitochondria. On the other hand, in the in vivo experiments, following light irradiation (100 J/cm2), retarded tumor growth was significant in mice treated with Radachlorin®, as compared to the control group. Taken together, we propose that PDT after the application of Radachlorin® may induce the Golgi apparatus-mediated apoptosis of cervical cancer cells in vitro, and also be effective in the mice system.

Modification of renin isoelectric heterogeneity in Goldblatt hypertensive rat

1985 ◽  
Vol 248 (6) ◽  
pp. E694-E698 ◽  
Author(s):  
F. M. Sessler ◽  
R. L. Malvin
Keyword(s):  
Isoelectric Focusing ◽  
Rat Kidney ◽  
Venous Blood ◽  
Renin Activity ◽  
Hypertensive Rat ◽  
Isoelectric Points ◽  
The Difference ◽  
Cortical Slices

Six forms of renin have been described in rat kidney. Different stimuli resulted in secretion of unique profiles of those forms. We studied their storage and secretion in the two-kidney, one-clip Goldblatt hypertensive rat (GHR). Renal venous blood, kidney homogenates, and incubation media from cortical slices were subjected to isoelectric focusing. In all samples tested, six peaks of renin activity were found with isoelectric points at pH 5.90, 5.70, 5.40, 5.20, 5.00, and 4.80. The quantity of renin activity for each form was expressed as a percentage of the total recovered from the gel. In control kidneys the profile of renin stored and that released by in vitro slices were similar. However, in plasma, the percentage of renin focusing at the more basic pH was decreased. This is in agreement with other work showing that the liver removes the more basic forms more rapidly than the acidic forms. The clipped kidney of GHR secreted, both in vivo and in vitro, a profile of renin forms that was significantly different from the control kidney. The difference was expressed by an increase in the secretion of the more acidic forms by the clipped kidney. It is hypothesized that changes in the secretory profile of renin may reflect changes in storage and synthesis of those forms.

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