Biomedical subjects

J St-Louis

Publications and source records attributed to J St-Louis.

At least 19 recordsLinked to original sources

PubMed2006

Placental oxidative stress in a rat model of preeclampsia.

The onset of preeclampsia is associated with increased maternal insult that could affect placental function. By increasing sodium intake (0.9% or 1.8% NaCl in drinking water) during the last week of gestation in the rat, we developed an animal model that shows many characteristics of preeclampsia such as increased blood pressure, decreased circulatory volume and diminished activity of the renin-angiotensin-aldosterone system. The aim of the present study was to determine in this model whether maternal perturbations in pregnancy lead to placental oxidative stress. Sprague-Dawley pregnant rats receiving salted-water were compared to not-supplemented pregnant rats. Markers of oxidative stress, ensuing cell death, and changes in the production of vasoactive substances (prostanoids: thromboxane, TxB(2); and prostacyclin, PGF(1alpha)) and the pro-inflammatory cytokine tumour necrosis factor-alpha (TNF-alpha) were measured in the placenta. In tissue from pregnant rats on 1.8% NaCl supplement, 8-iso-PGF(2alpha) levels, TxB(2)/6-keto-PGF(1alpha) ratios, total TNF-alpha RNA expression, as well as the apoptotic index (Bax/Bcl-2 ratio) and endothelial nitric oxide synthase protein expression increase while total glutathione content decreases. These findings demonstrate that maternal insult during gestation induced an imbalance in the oxidative environment in the placenta favouring oxidation. This was accompanied by an increased synthesis of vasoconstrictive substances and TNF-alpha by the placenta as well as the increased rate of placental cell apoptosis.

Animals↗

PubMed2005

Can activated recombinant factor VII be used to postpone the exposure of infants to factor VIII until after 2 years of age?

Two retrospective studies have suggested that exposure to factor VIII (FVIII) in early infancy is associated with an increased risk of FVIII inhibitor development. We prospectively studied 11 infants who needed replacement therapy for bleeding episodes before the age of 2 years. They received activated recombinant factor VII (rFVIIa) concentrate on demand, with the intention of postponing their first exposure to FVIII after 2 years of age. Thirty-three bleeding episodes were treated with 154 doses of rFVIIa with no evidence of adverse effect. Bleeding was controlled in 27 of 33 episodes. Mouth bleeds were most difficult to treat. The use of rFVIIa allowed postponement of the use of FVIII for a mean of 5.5 months (median 4, range 0-12) but in only three of 11 children could be the first exposure to factor postponed after the age of 2 years. With this modest effect of rFVIIa in postponing the first exposure to FVIII, more convincing evidence for the benefit of such a postponement will have to be demonstrated before rFVIIa could be recommended for this indication.

Age Factors↗

PubMed2003

Optimization of storage conditions for diluted working solutions of porcine factor VIII and performance of the Bethesda assay for the determination of antiporcine FVIII inhibitor titres.

The use of porcine factor VIII (FVIII) (Hyate:C, Ipsen) has proven to be very successful in treating patients with FVIII inhibitors. The best way to predict the usefulness of porcine FVIII therapy, and/or to estimate the appropriate treatment dose in a given patient, is to measure the patient inhibitor titre against porcine FVIII with the Bethesda assay, using porcine FVIII as the source of FVIII in the assay. The goals of the present study were to (1) find the optimal storage temperature, diluent and concentration for a working solution of porcine FVIII to be used as the source of FVIII for the porcine Bethesda assay, (2) assess the reliability of the labelled FVIII units in the preparation of such working solutions of porcine FVIII and (3) compare the inhibitor titres determined by the Bethesda assay using both porcine and human standard reference curves for measuring residual FVIII. The results of the present study demonstrate that a ready-to-use working solution of 1 U mL(-1) of Hyate:C diluted in human FVIII deficient plasma, either containing or deficient in von Willebrand factor antigen, is stable for up to 12 months, at -20 degrees C. The preparation of the 1 U mL(-1) working solution could be reliably calculated based on the units indicated on the vial label. Finally, using the human standard curve yields similar results to using the porcine standard curve for measuring any titre of allo- or auto-antibody against FVIII in the Bethesda assay, using Hyate:C as the source of FVIII. These findings are of practical value when performing a porcine FVIII-based Bethesda assay.

Animals↗

PubMed2003

Vascular responses to alpha-adrenergic stimulation and depolarization are enhanced in insulin-resistant and diabetic Psammomys obesus.

Since vascular complications often accompany diabetes, we examined the influence of the endothelial lining on vascular reactivity in Psammomys obesus, a desert gerbil that acquires insulin resistance and diabetes when exposed to a laboratory diet. Vasoconstriction to phenylephrine and depolarizing KCl, as well as carbachol endothelium-dependent relaxation, were assessed in rings of thoracic aortae obtained from three groups: (i) group A, normoglycemic-normoinsulinemic; (ii) group B, normoglycemic-hyperinsulinemic, and (iii) group C, hyperglycemic-hyperinsulinemic animals. As expected, marked hypertriglyceridemia and hypercholesterolemia characterized groups B and C, which developed enhanced contractile responsiveness to phenylephrine and KCl compared with controls (group A). Furthermore, both experimental groups displayed a significant decrease in endothelium-dependent relaxation to carbachol. Altered lipid profiles are considered to play some role in the observed modification of aortic reactivity. Overall, our data indicate that vascular contractile responsiveness is enhanced early in the development of insulin resistance and diabetes in the female P. obesus.

Adrenergic alpha-Agonists↗

PubMed2001

Blockade of angiotensin receptor subtypes in arcuate uterine artery of pregnant and postpartum rats.

During pregnancy, uterine circulation undergoes hypertrophy and hyperplasia. We investigated the effects of angiotensin (Ang) II receptor subtype (AT(1)/AT(2)) blockade on increased responses to the peptide during reversible remodeling of the uterine vasculature in pregnant and postpartum rats. Uterine arcuate arteries were set up in wire myographs for microvessel and submitted to a tension equivalent to 50 mm Hg transmural pressure. Cumulative concentration-response curves to Ang II were measured in the absence and presence of losartan on the same vascular segment. A similar protocol was repeated in the presence of PD 123,319, an AT(2) receptor blocker, again in the absence and presence of losartan. Responses to Ang II on the arcuate artery increased markedly during pregnancy and returned to the prepregnant level within 12 days postpartum. Losartan (10(-7) mol/L) produced a parallel right shift of the concentration-response curve to Ang II in all groups of tissues, but potency of the AT(1) receptor blocker was reduced at the end of pregnancy and in the early postpartum period. PD 123,319 (10(-7) mol/L) significantly increased maximum response to Ang II in arterial segments of the nonpregnant, term-pregnant, and 5 days postpartum rats. AT(1) receptor expression was decreased in arcuate arteries of term-pregnant rats. These results show that contractile responses to Ang II on the uterine arcuate artery of the rat are mediated by the AT(1) receptor and that blockade of AT(2) receptors potentiated responses to the peptide. They also indicate that, in uterine vessels, AT(2) receptor stimulation interferes with Ang II responses, but this effect is decreased in uterine arcuate arteries in the peripartum period.

Angiotensin II↗

PubMed2000

Functional alteration of dihydropyridine-sensitive Ca(2+) channels in the adrenal glomerulosa of pregnant rats.

Our previous work on aldosterone secretion suggested that dihydropyridine-sensitive calcium channels, one type of voltage-dependent calcium channels (VDCC), are functionally impaired in adrenal capsule preparations from the pregnant rat. The aim of this study was to determine whether, during pregnancy, the density and/or activity of these channels is altered in the adrenal zona glomerulosa. These VDCC measured with [(3)H]nitrendipine binding were not different between membrane preparations of nonpregnant and pregnant rats. Western blots were performed using two different antibodies, a polyclonal (PcAb) directed against the alpha(1)-subunit of VDCC and a monoclonal (McAb) that recognizes an intracellular domain of that protein. McAb immunoreactivity showed a significant decrease in preparations from pregnant rats, whereas no difference was observed with PcAb. VDCC activity was estimated by (45)Ca(2+) uptake in isolated adrenal cortex and by intracellular calcium concentration ([Ca(2+)](i)) in adrenal glomerulosa cells with the Ca(2+) probe fura PE3. These measurements revealed that KCl stimulation produced greater Ca(2+) influx in nonpregnant than in pregnant rats. Nifedipine (a blocker of VDCC) inhibited this stimulation only in nonpregnant rats, whereas BAY K 8644 (an activator of VDCC) increased Ca(2+) influx in pregnant rats only. These data suggest that, during pregnancy, the altered regulation of calcium homeostasis in adrenal glomerulosa is linked to a conformational alteration of VDCC.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed2000

Effects of potassium channel modulators on myotropic responses of aortic rings of pregnant rats.

The contribution of potassium channels [ATP-sensitive potassium (K(ATP)) and high-conductance calcium-activated potassium (BK(Ca)) channels] in the resistance of aortic rings of term pregnant rats to phenylephrine (Phe), arginine vasopressin (AVP), and KCl was investigated. Concentration-response curves to tetraethylammonium (TEA), a nonselective K(+) channel inhibitor, were obtained in the absence or presence of KCl. TEA induced by itself concentration-dependent responses only in aortic rings of nonpregnant rats. These responses to TEA could be modulated in both groups of rings by preincubation with different concentrations of KCl. Concentration-response curves to Phe, AVP, and KCl were obtained in the absence or presence of cromakalim or NS-1619 (K(ATP) and BK(Ca) openers, respectively) and glibenclamide or iberiotoxin (K(ATP) and BK(Ca) inhibitors, respectively). Cromakalim significantly inhibited the responses to the three agonists in a concentration-dependent manner in both groups of rats. Alternatively, in the pregnant group of rats, glibenclamide increased the sensitivity to all three agonists. NS-1619 also inhibited the response to all agonists. With AVP and KCl, its effect was greater in aortic rings of pregnant than nonpregnant rats. Finally, iberiotoxin increased the sensitivity to all three agents. This effect was more important in aortic rings of nonpregnant rats and was accompanied by an increase of the maximal response to Phe and AVP. These results suggest that potassium channels are implicated in the control of basal membrane potential and in the blunted responses to these agents during pregnancy.

Animals↗

PubMed1999

Induction of intrauterine growth restriction with a low-sodium diet fed to pregnant rats.

OBJECTIVE: A low-sodium diet fed to female rats before mating through parturition leads to pups of lower weight. We characterized the effect of low dietary sodium during the last week of gestation (after fetal organogenesis) on fetal and maternal homeostasis. STUDY DESIGN: Pregnant Sprague-Dawley rats were randomly assigned to a control group or to a group fed a low-sodium diet from gestational days 15 through 22. Systolic blood pressures were measured throughout pregnancy. On day 22 plasma volume was measured and blood samples were taken for electrolyte and hormonal measurements. Fetal and placental weights were also determined. RESULTS: Plasma renin activity and aldosterone level were significantly higher in the experimental group than in the control group. Plasma volume was significantly lower in pregnant rats receiving a low-sodium than in those receiving a control diet. Rats receiving a low-sodium diet had pups of lower weight and length (4.45 +/- 0.22 g, 3.90 +/- 0.06 cm) than pups of the control group (5.21 +/- 0.12 g, 4.10 +/- 0.02 cm). Pups born to mothers with low-sodium diets recuperated from intrauterine growth restriction by 14 days after birth. CONCLUSION: These data indicate that a low-sodium diet given to pregnant rats for the last 7 days of gestation leads to reduced plasma volume expansion and fetal growth restriction. This could prove to be a simple animal model for studying the relationship between maternal plasma volume and fetal growth.

Aldosterone↗

PubMed1999

Reactivities to serotonin and histamine in umbilical and placental vessels during the third trimester after normotensive pregnancies and pregnancies complicated by preeclampsia.

OBJECTIVE: The aim of the study was to evaluate responses of umbilical and placental arteries and veins to serotonin and histamine after normotensive pregnancies and pregnancies complicated by preeclampsia. STUDY DESIGN: Each pair of placentas from a normotensive woman and a woman with preeclampsia was matched for gestational age. Rings of these vessels were prepared and mounted in tissue baths under their respective optimal passive tension. Cumulative concentration-response curves to serotonin and histamine were measured. RESULTS: Responses to serotonin were decreased in umbilical vessels from the preeclampsia group with respect to the normotensive group. This is reflected by reduced maximum responses and sensitivity (negative logarithm of the 50% effective concentration) to serotonin. Maximum response to serotonin was significantly decreased in placental vein rings from the preeclampsia group. We recorded a decreased maximal response to histamine in placental vein rings from pregnancies complicated by preeclampsia with respect to those from normal pregnancies. Among normotensive women there was a significant positive linear relationship between neonatal weight and sensitivity to serotonin in umbilical and placental veins. This relationship was totally absent in preeclampsia. Sensitivity to histamine was linearly related to neonatal weight in umbilical vessels of the pooled results of both experimental groups. CONCLUSION: The vasoconstrictive effects of serotonin, but not those of histamine, are decreased in umbilical and placental vessels after preeclampsia. Sensitivities to serotonin and histamine change in umbilicoplacental vessels during the third trimester. Altered reactivity to serotonin may play a significant role in the reduction of umbilicoplacental blood flow in preeclampsia.

Dose-Response Relationship, Drug↗

PubMed1999

Modulation of calcium mobilization in aortic rings of pregnant rats: Contribution of extracellular calcium and of voltage-operated calcium channels.

Pregnancy is associated with decreased vascular responsiveness to vasopressor stimuli. We have tested the involvement of Ca2+ mobilization in myotropic responses of aortic rings obtained from pregnant and virgin rats. Contractions of the rings to phenylephrine, in the absence of calcium in the bathing medium, were lower in tissues from virgin than from pregnant rats. Concentration-response curves to CaCl2 that were measured after stimulation by phenylephrine in the absence of Ca2+ were shifted to higher levels of contraction. This was not observed when KCl was used to prestimulate the aorta. D-600, a phenylalkylamine calcium channel blocker, similarly inhibited these responses to CaCl2 in tissues from both pregnant and virgin animals. D-600 exerted a concentration-dependent inhibition of responses to phenylephrine and KCl. However, the calcium antagonist was less effective in aortic rings of pregnant than of virgin rats. Basal 45Ca2+ uptake was lower in aortic rings from pregnant than from virgin rats, and Bay K 8644 was unable to reverse this difference. The time course of basal and stimulated (KCl) 45Ca2+ influx was lower in aorta of pregnant rats at all times studied. Moreover, when the intracellular calcium pools were emptied with phenylephrine, the refilling of these pools was delayed in aortic rings of pregnant rats. These results indicate an altered extracellular calcium mobilization of aortic rings from pregnant rats. These changes may be due to a functional alteration of the voltage-operated calcium channels during pregnancy.

Animals↗

PubMed1998

Tyrosine kinase and MAPK inhibition of TNF-alpha- and EGF-stimulated IEC-6 cell growth.

The role of TNF-alpha in modulating intestinal crypt cell growth was examined, in comparison with EGF. Both significantly increased IEC-6 cell proliferation. Neither EGF nor TNF-alpha overcame the inhibitory effect on growth exerted by the tyrosine kinase inhibitor genistein. Immunoblots with phosphotyrosine antibodies showed increased tyrosine phosphorylation of IEC-6 cell proteins in response to EGF and TNF-alpha stimulation. TNF-alpha increased ERK1 and ERK2 MAPK phosphorylation. A MAPK assay confirmed the increased activity upon TNF-alpha stimulation. Selective inhibition of MAPK activation by PD98059 resulted in a dose dependent inhibition of TNF-alpha or EGF-induced IEC-6 cell growth. These findings suggest a role for TNF-alpha in the regulation of intestinal epithelial cell growth and that the mitogenic effect of TNF-alpha requires protein tyrosine phosphorylation and MAPK activation.

Animals↗

PubMed1997

Effects of dihydropyridines on aldosterone secretion in adrenal capsule preparations from pregnant rats.

The primary aim of this study was to determine when sensitivity in the aldosterone response to extracellular potassium (K+) decreases during pregnancy. Second, it tested the hypothesis that calcium channel alterations occur in the adrenal cortex during pregnancy. The decreased sensitivity to K+, observed at 22 days of gestation, was not evident at 15 days and between 18 and 36 h postpartum. Increases in extracellular calcium concentration heightened sensitivity to K+ in adrenal capsule preparations derived from nonpregnant rats but had no effect in pregnant animals. The influence of nifedipine and BAY K 8644 (blocker and activator, respectively, of voltage-operated calcium channels) on the aldosterone response to K+ and to adrenocorticotropic hormone (ACTH) was studied. Sensitivity to K+ in nonpregnant rats decreased in the presence of nifedipine and became similar to that in pregnant rats. Responses to ACTH were not affected by nifedipine. BAY K 8644 produced a larger increase in sensitivity in adrenal capsule preparations from pregnant than from nonpregnant rats, leading to superposition of the two dose-response curves to K+. These results indicate that voltage-operated calcium channels involved in aldosterone secretion are functionally impaired during pregnancy.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1997

Increased reactivity of rat uterine arcuate artery throughout gestation and postpartum.

Significant modifications of the uterine circulation are observed during pregnancy, with uterine circulation accounting for up to 11% of cardiac output at the end of pregnancy. We studied the reactivity of the uterine microcirculation to determine the time course of uterine mechanical and pharmacological alterations during pregnancy and postpartum. Arcuate artery segments, obtained from virgin, pregnant (7, 14, and 22-23 days), and postpartum (5 days) rats, were set up in wire myographs for microvessels under a passive tension equivalent to a transmural pressure of 50 mmHg (L50). Cumulative concentration-response curves to angiotensin II (ANG II), phenylephrine (PE), and potassium chloride (KCl) were measured. Diameter of the arcuate artery at L50 increased progressively until term from 108 +/- 4 microns in virgins to 188 +/- 9 microns at day 22 of pregnancy. This increase in diameter was partially reversed at day 5 postpartum (151 +/- 9 microns). Surprisingly, the passive length-tension relationship on arcuate arteries showed greater stiffness from day 14 of pregnancy through day 5 postpartum. The maximum response of the arteries to ANG II was markedly increased during pregnancy (from 0.78 +/- 0.02 to 1.43 +/- 0.09 mN/mm at day 22) and was already evident at day 14 (1.20 +/- 0.07 mN/mm) but was reversed in postpartum rats (0.81 +/- 0.04 mN/mm, nonsignificant). Similar results were obtained for maximum responses to PE and KCl, but the reversal at day 5 postpartum was only partial. Sensitivity (measured as the negative log of the concentration of stimulant required to produce 50% of the maximum response) of the uterine arcuate artery to the three vasopressors increased during the postpartum period and also at day 21 of pregnancy with PE and day 14 with KCl. The present results show that the uterine arcuate artery doubles in diameter during pregnancy. This increase in diameter is accompanied by increased stiffness of the vessel and heightened responsiveness to ANG II, PE, and KCl. These data demonstrate that pregnancy induces changes in reactivity of the rat uterine arcuate artery that appear to be linked to modifications in the mechanical properties of the vessel, at least for ANG II and PE.

Analysis of Variance↗

PubMed1997

Smooth muscle contractility and protein tyrosine phosphorylation.

During the last 5 years several studies have documented an involvement of protein tyrosine kinases (PTKs) in smooth muscle contraction and Ca2+ mobilization. Most of these studies have utilized highly selective inhibitors of PTKs, genistein and tyrphostin and have shown that these inhibitors attenuated smooth muscle contraction induced by growth factors-epidermal growth factor (EGF) and platelet derived growth factor (PDGF) and several vasoactive peptides. It has also been demonstrated that inhibitors of protein tyrosine phosphatases (PTPases) such as vanadate and pervanadate mimic growth factors and vasoactive peptides in causing the contraction of smooth muscle. In this brief review, we have summarized some of the recent observations suggesting a possible link between protein tyrosine phosphorylation pathway and smooth muscle contraction.

Animals↗

PubMed1996

Characteristics of ANP-binding sites in the adrenal capsules of term-pregnant rats.

Significant increases of circulatory volume and plasma aldosterone levels are observed in pregnancy. We investigated whether a decrease of atrial natriuretic peptide (ANP) receptors in the adrenal zona glomerulosa (ZG) could explain the marked elevation of plasma aldosterone occurring during pregnancy. 125I-ANP binding was measured in competition experiments using rANP(1-28), ANP(4-23), a truncated analog which has high specificity for the ANP-C receptor, or a combination of both. Western blot experiments were also performed with an investigation into the effect of ANP on aldosterone secretion in adrenal capsule suspensions. 125I-ANP binding on adrenal ZG membranes was displaced by ANP(1-28) with an affinity (Kd) of 313 +/- 39 and 323 +/- 60 pM (NS) for pregnant and non-pregnant rats, respectively. The density of sites (Bmax) decreased slightly but not significantly during pregnancy. Displacement experiments with ANP(4-23) demonstrated a Bmax of 137 and 134 fmol/mg of proteins (NS) for pregnant and non pregnant rats, respectively. Studies were performed to block the ANP-C site. Displacing the remaining 125I-ANP binding with ANP(1-28) led to an affinity constant and receptor density which were not significantly different between the two groups of rats. The results obtained with Western blots showed a single band of 123 kDa with no significant variations in ANP-R1 receptors in the ZG during gestation. The sensitivity of potassium-, ACTH- or angiotensin II-stimulated aldosterone secretion to ANP was not altered by gestation. These data show that the apparent hyperaldosteronism found in normal term-pregnant rats is not the consequence of modifications in the affinity, number and properties of ANP receptor types or in the sensitivity of the aldosterone response to ANP.

Adrenocorticotropic Hormone↗

PubMed1996

Nitric oxide in retinal and choroidal blood flow autoregulation in newborn pigs: interactions with prostaglandins.

The role of nitric oxide (NO) as well as its interaction with prostaglandins (PG) in setting the limits of autoregulation of retinal blood flow (RBF) and choroidal blood flow (ChBF) were studied in newborn pigs (1-5 d old). Blood flows were measured by the microsphere technique. Low and high ocular perfusion pressures (OPP) were induced by inflating balloon-tipped catheters placed at the aortic root and isthmus, respectively. Animals were treated with the NO synthase inhibitors, NG-nitro-L-arginine methyl ester (L-NAME, 1 mg/kg followed by 50 mu g/kg/min; n = 12) or NG-monomethyl-L-arginine (L-NMMA, same dose as L-NAME; n = 3), or with saline (n = 12). In separate animals (n = 42), guanosine 3',5'-cyclic monophosphate (cGMP), the second messenger for NO, and PG were measured at an average OPP of 90 mm Hg and 125 +/- 6 mm Hg; cGMP levels served as an index of NO release. The effect of the NO donor sodium nitroprusside on choroidal vessel diameter was determined using video imaging of isolated eyecup preparations. In control animals RBF was constant only within a range of 30 to 80 mm Hg OPP (r = 0.03, p > 0.9). There was no autoregulation of ChBF which increased as a function of OPP (tau = 0.58-0.72, p < 0.01). L-NAME and L-NMMA prevented a change in RBF and ChBF from 30 to 146 mm Hg [the highest OPP studied (r < 0.3, p > 0.15)] and caused an increase in retinal as well as choroidal vascular resistance as OPP was raised; these agents did not affect ocular blood flow at OPP < 30 mm Hg. Elevated OPP caused increases in cGMP, 6-keto-PGF1alpha, and PGE2 in the choroid (a vascular tissue), which were prevented by L-NAME and L-NMMA. Sodium nitroprusside caused a dilatation of choroidal vessels in isolated eyecup preparations, which was significantly attenuated by indomethacin. Data suggest a role for NO in the autoregulation of RBF and ChBF in the newborn such that a release of NO during a rise in OPP prevents adequate constriction necessary for maintaining RBF and ChBF constant; data also suggest that the vasodilator effect of NO might in part be mediated through a release of PG.

Animals↗

PubMed1996

Increase of aldosterone secretion in adrenal cortex suspensions derived from pregnant rats.

Plasma aldosterone levels increase markedly during pregnancy, but not in proportion to the rise in plasma renin activity (PRA). We have developed a reliable in vitro method to investigate aldosterone secretion during pregnancy. With this method, we have assessed the potency and effectiveness of ACTH and potassium to stimulate this secretion during pregnancy. Adrenal capsules from pregnant and nonpregnant rats were incubated in 1 ml of culture medium within wells of tissues culture plates. The cortex was transferred every 20 min to another well containing fresh medium with or without ACTH or potassium. Basal and stimulated aldosterone secretions were not significantly affected by time under our experimental conditions. The glands remained responsive to stimulants throughout the study period (360 min). Plasma aldosterone levels and PRA were increased during pregnancy. Basal aldosterone secretion in adrenal cortex suspensions from pregnant rats showed a 1.6-fold increment (P < 0.001) in comparison with nonpregnant controls. The dose-response curves of ACTH were not significantly different between pregnant and nonpregnant animals. However, sensitivity to potassium was significantly reduced during pregnancy, as demonstrated by an elevated ED50 (4.01 +/- 0.08 vs 4.71 +/- 0.07 mM for nonpregnant versus pregnant rats respectively, P < 0.001). These data indicate that adrenal cortex suspensions are a reliable and reproducible way to study aldosterone secretion during pregnancy. They reveal that, during pregnancy, sensitivity of potassium to stimulate aldosterone secretion is decreased while the response to ACTH is not affected.

Adrenal Cortex↗

PubMed1995

Angiotensin II receptor subtypes in the adrenals of pregnant rats.

During human and rat pregnancy, several hemodynamic and endocrine processes are markedly modified. These include activation of the renin-angiotensin system (RAS) and increase of plasma aldosterone. However, the rise of plasma aldosterone is greater than expected from the elevation of RAS activity. Gestational alterations in angiotensin II receptors (AT receptor) in the adrenal could explain this apparent hyperaldosteronism. This study was conducted to determine differences between AT receptor subtypes in the adrenal glands of non-pregnant and pregnant (22 days) rats. Using plasma membrane preparations from adrenal glomerulosa and medulla, we determined receptor density and affinity with 125I-angiotensin II (ANG II); the AT receptor subtypes were assessed by displacement of 125I-ANG II binding with subtype-specific antagonists (DuP753 and PD123319). In zona glomerulosa of non-pregnant and pregnant rats, AT1 receptors predominated (approximately 80%) with no statistical difference in receptor density (Bmax) and affinity (Kd) and the ratio of receptor subtypes between the two groups of rats. In adrenal medulla of both groups of rats, the major portion of 125I-ANG II binding (60-70%) was displaced by the AT2 receptor antagonist, PD123319. Neither Bmax nor Kd differed in this tissue during gestation. The results for AT1 receptor density were confirmed by Western blot. Northern blot analysis showed that AT1 mRNA level in the adrenal is not modified by gestation. These results indicate that the number, the affinity and the transcription of the AT1 receptor in the adrenal are not altered during pregnancy, indicating that the rise in aldosterone secretion during pregnancy could not be explained by increase of AT1 receptors in the zona glomerulosa, or modification of AT1/AT2 ratio.

Adrenal Glands↗