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J St-Louis

Publications and source records attributed to J St-Louis.

At least 55 records · Page 3Linked to original sources
PubMed1988

Vasorelaxation and vascular binding sites for atrial natriuretic peptide in pregnant rats.

To investigate the role of atrial natriuretic peptide (ANP) in pregnancy, we measured, in cyclic and pregnant female rats (9- and 21-days pregnant), the vascular responsiveness to ANP using helical strips of the thoracic aorta, the binding characteristics of 125I-labeled ANP in a membrane preparation of the mesenteric vascular bed, and the plasma level and the atrial content of immunoreactive ANP (IR-ANP). On aorta strips, concentration-response (C-R) curves to phenylephrine (PE) were measured and were slightly displaced to the right in the aorta of both groups of pregnant rats in comparison with the cyclic rats. There was a potentiation of the relaxant response of ANP on the PE-precontracted aortic strips of 9-day pregnant rats but it was not statistically modified in tissues of 21-day pregnant rats in comparison with strips from cyclic rats. The number of binding sites (Bmax) for ANP in the mesenteric vascular bed was similar in cyclic rats and the two groups of pregnant rats. The dissociation constant (KD) of ANP was lower in 9-day pregnant rats than in cyclic and 21-day pregnant ones. Plasma IR-ANP was not different in 9-day pregnant rats and cyclic rats but was markedly decreased at the end of gestation. Atrial content of IR-ANP increased at the end of gestation, but not in midpregnancy in comparison with cyclic rats. These results indicate that despite the reported important increase in blood volume during gestation the secretion of ANP is not increased and suggest that the ANP-volume relationship is reset during pregnancy in the rat.

Animals↗
PubMed1988

Vascular vasopressin receptors in renal hypertensive rats.

We investigated the plasma concentration of [Arg8]-vasopressin (AVP), the density of AVP-binding sites on membranes from the mesenteric vascular bed, and the pressor response to AVP of the perfused mesenteric vasculature in vitro from one-kidney, one-clip (1K, 1C) and two-kidney, one-clip (2K, 1C) Goldblatt hypertensive rats. The plasma concentration of AVP was increased in 1K, 1C hypertensive rats. The density of AVP-binding sites was similar in sham-operated normotensive, in 2K, 1C hypertensive, and in uninephrectomized rats but was significantly decreased in 1K, 1C hypertensive rats (P less than 0.05). The binding affinity of AVP was similar in all experimental groups. Vasoconstrictor response to AVP was increased in 2K, 1C hypertensive rats (27% higher than sham-operated normotensive rats, P less than 0.05). Responses in 1K, 1C hypertensive rats were similar to those of uninephrectomized rats. Our results indicate that together with an increased concentration of AVP in plasma the number of vascular AVP-binding sites is decreased in 1K, 1C hypertensive rats, whereas both are unaltered in 2K, 1C hypertensive rats. Vascular AVP receptors appear to be regulated inversely to plasma AVP concentrations. Pressor responsiveness to AVP is normal in 1K, 1C hypertensive rats and exaggerated in 2K, 1C hypertensive rats. Increased vascular responsiveness to AVP may occur independently of the regulation of AVP receptors and may contribute to elevation of blood pressure in renal hypertension in the rat.

Animals↗
PubMed1987

Decreased in vitro responses to vasoconstrictors during gestation in normotensive and spontaneously hypertensive rats.

We have investigated the in vitro vascular responses to vasoconstrictor agents in pregnant normotensive (Sprague-Dawley (SDR) and Wistar-Kyoto (WKR] and spontaneously hypertensive rats (SHR) to measure the sensitivity and contractility of blood vessels of pregnant rats. In the perfused mesenteric vascular bed from rats on the 21st day of gestation, the concentration-response curves for the increase in perfusion pressure by arginine8-vasopressin and norepinephrine were displaced to the right by comparison to nonpregnant female rats when all strains of rats were considered together. The increase in EC50 to both agents in pregnant rats was from 1.3- to 2.7-fold in the mesenteric bed; SDR showed the highest increase in EC50, followed by SHR and WKR. No consistent effect was observed on the maximum response. Similar results were obtained in isolated portal veins for angiotensin II and norepinephrine, except that the increase in EC50 in pregnant rats was smaller in magnitude (from 1.0 to 1.7) and followed the same interstrain pattern. These data show that the decreased responsiveness to vasoconstrictor agents in pregnant rats observed in vitro is similar in normotensive and hypertensive rats and suggest that the factor(s) responsible for this effect is a phenomenon affecting vascular smooth muscle in both arteries and veins.

Angiotensin II↗
PubMed1987

Decreased density of vascular receptors for atrial natriuretic peptide in DOCA-salt hypertensive rats.

We have previously found that vascular receptors for atrial natriuretic peptide (ANP) in the rat are down-regulated by volume expansion. For this reason vascular ANP receptor density and affinity were examined in a model of volume-expanded hypertension, the deoxycorticosterone acetate (DOCA)-salt hypertensive rat. The density of mesenteric vascular ANP binding sites was decreased in DOCA-salt hypertensive rats from a control value in uninephrectomized rats of 203 +/- 25 fmol/mg protein to 60 +/- 13 fmol/mg protein (p less than 0.01). The sensitivity of norepinephrine-precontracted aorta to ANP was significantly reduced in DOCA-salt hypertensive rats (p less than 0.001). DOCA-salt hypertensive rats infused intravenously for 4 days with ANP, 100 to 300 ng/hr, did not experience a lowering of blood pressure, in contrast to the significant reduction in blood pressure seen in two-kidney, one clip Goldblatt hypertensive rats similarly infused. In the latter there was no natriuretic response to ANP, while in the DOCA-salt hypertensive rats natriuresis occurred without lowering of blood pressure. In the DOCA-salt hypertensive rats plasma ANP concentration was increased to 68 +/- 8 fmol/ml from 10 +/- 1 fmol/ml in uninephrectomized rats. In conclusion, raised ANP concentration in plasma of volume-expanded hypertensive rats (DOCA-salt hypertension) may result in decreased density of ANP vascular receptors. These results suggest that a decrement in the number of ANP receptors may be a cause of decreased sensitivity of vascular responses to ANP in vitro and resistance to the blood pressure-lowering action of ANP in vivo.

Animals↗
PubMed1987

Heart rate reflex responses during gestation in normotensive and spontaneously hypertensive rats following angiotensin II and vasopressin.

Gestation in the human and in rats is accompanied by a decrease in blood pressure and a reduction of the pressor response to vasoconstrictor agents. In humans, the decreased vascular reactivity to angiotensin II (AII) may occur simultaneously with a state of increased baroreceptor sensitivity. We have consequently evaluated the heart rate response to elevation of blood pressure following administration of either AII or arginine8-vasopressin (AVP) in conscious unrestrained, nonpregnant, or term-pregnant normotensive rats (Sprague-Dawley, SDR; Wistar-Kyoto, WKR) and in spontaneously hypertensive rats (SHR). The decrease in heart rate in response to increase in blood pressure by AII in nonpregnant animals was similar in SDR and SHR, but much greater in WKR. The heart rate response to increase in blood pressure by AVP was similar in all three strains of cycling rats. Gestation (20th day) did not change the heart rate response to increase in blood pressure by AII in normotensive animals, but increased slightly the reflex responses in SHR, as shown by a significant increase of the slope of the relationship of the decrement in heart rate versus the increment of blood pressure. The heart rate response to increase in blood pressure by AVP was greater during gestation in normotensive SDR and WKR, but not in SHR. These results show that the heart rate responses to an increase in blood pressure by vasoconstrictor peptides is dependent on the strain of animals used and suggest that the baroreceptor reflexes play a minor role in the blunted effect of vasconstrictor agens at the end of gestation in normotensive and spontaneously hypertensive rats.

Angiotensin II↗
PubMed1986

Vasopressin responses and receptors in the mesenteric vasculature of estrogen-treated rats.

The effect of treatment with estrogens on the biological activity of arginine8 vasopressin (AVP) in the in vitro perfused mesenteric vascular bed and on the binding characteristics of [3H]AVP on membranes prepared from the same vascular bed was studied. Female rats treated with estradiol (400 micrograms/24 h sc), compared with ovariectomized rats, had an increase in the maximum response to AVP (from 128 +/- 3 to 153 +/- 3 mmHg) in the perfused preparation and an increase in the density of AVP binding sites (from 402 to 732 fmol/mg protein) in the membrane preparation. In male rats, the injection of estradiol increased the maximum response to AVP (from 109 +/- 4 to 137 +/- 3 mmHg) and the density of AVP binding sites (from 289 to 519 fmol/mg protein). The effective concentration producing 50% of maximum response of AVP in the perfused preparation was higher in male than in female rats, while the Kd in the binding experiments was similar in the four experimental groups. Our results show that estrogens upregulate the number of AVP binding sites, leading to an increase in the pressor response to AVP in the rat mesenteric vascular bed.

Animals↗
PubMed1985

Chronic decrease of blood pressure by rat relaxin in spontaneously hypertensive rats.

Relaxin is an ovarian polypeptide hormone which is present in large amounts in the rat during the second half of gestation. During this period, blood pressure declines markedly, especially in spontaneously-hypertensive rats (SHR). To test the hypothesis that relaxin might be implicated in this decrease in blood pressure, we infused the hormone in female non-pregnant rats by means of an osmotic mini pump. Our results show that intravenous infusion of purified rat relaxin (1.8 micrograms/day) markedly reduced systolic blood pressure for at least 5 or 6 days in SHR. This decrease was highly significant from 24 hours after the beginning of the infusion and remained significant after 5 days. Rat relaxin was ineffective in control Wistar-Kyoto rats (WKY). Infusion of purified porcine relaxin (3.0 micrograms/day) also diminished blood pressure in SHR, but the effect was less pronounced and developed more slowly, reaching statistical significance on the fourth day of infusion. SHR not receiving relaxin maintained their original systolic blood pressure throughout the experiment. These results indicate that relaxin is involved in the regulation of blood pressure during gestation.

Animals↗
PubMed1985

Vascular and adrenal receptors for atrial natriuretic factor in the rat.

Previous studies have shown that atrial natriuretic factor, a powerful vasorelaxant of precontracted vessels, inhibits the secretion of aldosterone stimulated by angiotensin II, adrenocorticotropic hormone, and potassium. We now report the presence of specific binding sites for atrial natriuretic factor in rat blood vessels (mesenteric and renal arteries) and adrenal capsules. Radioiodinated synthetic atrial natriuretic factor bound to a single class of high-affinity (KD = 0.1 nM) low-capacity receptors in a particulate fraction from blood vessels and adrenals. Unrelated peptides did not displace atrial natriuretic factor. Fragments of atrial natriuretic factor displaced the labeled ligand with decreasing potency after cleavage at the N-terminal. The cleavage of the C-terminal tyrosine did not decrease the potency of atrial natriuretic factor, but further cleavage at the C-terminal dramatically reduced the affinity of the resulting peptides. The potency of the atrial natriuretic factor fragments in the radioligand assay was in proportion to their potency to inhibit aldosterone secretion by isolated rat glomerulosa cells. Our results suggest that these binding sites mediate the biological actions of atrial natriuretic factor in blood vessels and the adrenal, and that both receptors have similar specificities.

Adrenal Glands↗
PubMed1985

Solid-phase radioimmunoassay for relaxin.

A specific radioimmunoassay (RIA) for porcine relaxin is described in the present report, which also discusses its characterization in terms of its specificity and cross-reactivity to human and rat relaxin. The antibodies used in this assay were developed in rabbits immunized against highly-purified porcine relaxin. They were adsorbed on polystyrene tubes via incubation of a 1:40,000 antibody dilution for 24 hours. NIH relaxin was utilized for iodination by the Bolton-Hunter method and for the standard curve. The RIA was sensitive from 31.3 to 8,000 pg/tube of the porcine hormone. Rat relaxin cross-reacts with the anti-body, but the displacement curve produced by purified rat relaxin was shifted to the right by two orders of magnitude when compared to porcine relaxin. Displacement of 125I-porcine relaxin was also observed with the plasma of pregnant rat or woman, but about 100 times more plasma of these two species was required to produce the same displacement. No cross-reactivity was observed with human, bovine and porcine insulins. This RIA for relaxin will permit clinical evaluation of plasma relaxin concentrations during gestation and in different associated diseases. The concentrations of relaxin in human plasma obtained by this method might represent only a fraction of the actual concentration of the hormone due to low cross-reactivity of the anti-porcine relaxin with human hormone. It is also possible that relaxin is present in lower concentration in the plasma of pregnant woman in comparison to pregnant sow plasma.

Animals↗
PubMed1984

Biological action and binding sites for vasopressin on the mesenteric artery from normal and sodium-depleted rats.

We have recently demonstrated specific binding for 3H-arginine8-vasopressin (3H-AVP) to high affinity sites on membranes of rat mesenteric arteries. We have now measured the biological activity of this peptide (AVP) and analogues on the perfused rat mesenteric artery. There was a close relationship between the ED50 of agonists or the pA2 of antagonists on the perfused tissue and the relative potency (IC50) of analogues for displacing 3H-AVP from the membrane preparation. The ED50 measured was 67 +/- 7 ng for AVP and 7.2 +/- 1.1 microgram for oxytocin. In sodium-depleted rats we have observed an increase (27%) of the maximal response to AVP with no significant change in ED50 (from 2.8 +/- 1.0 X 10(-8) M to 1.3 +/- 0.2 X 10(-8) M). On the membrane preparation, the number of binding sites for 3H-AVP was increased from 71 +/- 17 fmole/mg protein (Kd 3.5 +/- 0.5 nM) to 115 +/- 10 fmole/mg protein (Kd 4.8 +/- 0.3 nM) in the sodium-depleted rat by comparison to control animals. These results suggest that AVP and its analogues interact in a similar manner in the in vitro perfused rat mesenteric artery and with the membrane receptors isolated from the same tissue. Receptors for AVP are increased in the mesenteric vascular bed by sodium depletion.

Animals↗
PubMed1982

Pharmacological studies on the action of relaxin upon KCl-contracted rat uterus.

The present experiments were designed to elucidate the pharmacological mechanism of the relaxing action of the ovarian hormone, relaxin, upon KCl-contracted rat uteri in vitro. Rat uterine segments were made to contract by superfusion with a physiological solution, in which 15% of the normal NaCl content had been replaced by an equimolar amount of KCl. The effect of relaxin, in reversing this contraction, was achieved in part by a direct action upon the tissue and in part (about 45% at the concentration of relaxin used) by the liberation of endogenous catecholamines which relax the uterus via beta-adrenergic activity. The effect of relaxin was reduced by propranolol, and it was not blocked by indomethacin, cimetidine or diphenhydramine. The effect of the ovarian peptide on uterine segments was potentiated in the presence of theophylline and indomethacin in the superfusing fluid. This effect of theophylline was shown to be insensitive to beta-adrenergic blockade. The results suggest that relaxin relaxes the KCl-contracted rat uterus in part by a direct inhibitory action upon the uterine muscle and in part by facilitating the release of intramural catecholamines. It is also suggested that relaxin may act via the production of cyclic AMP.

Animals↗
PubMed1982

Radioimmunoassay of corticotropin from plasma.

We describe a specific and highly sensitive radioimmunoassay for corticotropin (ACTH) in human plasma. As little as 1.9 pg of circulating ACTH can be detected per milliliter (0.44 pmol/L). ACTH is first extracted from plasma samples by adsorption onto pretreated Vycor glass powder, eluted from the adsorbent by acetone, and then lyophilized. For purification of 125I-labeled ACTH, a small octadecasilyl silica column is used. The mean (and SD) concentration of ACTH in plasma from 18 ostensibly normal subjects was 10.3 (4.3) pmol/L. After overnight suppression with dexamethasone in seven of these normal subjects, their ACTH values fell to 2.62 (1.3) pmol/L (p less than 0.0005). This assay will permit clinical evaluation of ACTH plasma concentrations in clinical investigation and of the effects of drug administration on circulating ACTH.

Adrenocorticotropic Hormone↗
PubMed1981

Relaxin inhibition of KCl-induced uterine contractions in vitro: an alternative bioassay.

The effect on the rat uterus of the ovarian peptide hormone, relaxin, has been studied in vitro. Partial (20%) replacement of the NaCl in physiological saline by KCl resulted in a strong contraction of the uterus which was reversed by relaxin. The preparation contracted by this level of KCl substitution was shown to be very sensitive to the action of extracts of pregnant sow ovaries containing relaxin in comparison with the ones contracted by higher and lower degrees of KCl substitution. The ovarian extracts induced a concentration-dependent reversal of the contraction of the uterus; this activity of relaxin increased with the degree of purification of the hormone. Relaxin induced a slowly developing relaxation whereas epinephrine relaxed the same preparation very rapidly until a plateau relaxation was reached. The concentration-response curves to relaxin at different states of purification were parallel and were also parallel and comparable in potency to the ones measured for similar preparations from other laboratories. These results suggest that rat uterus contracted in vitro by KCl-substituted saline should be a valuable and reproducible bioassay for relaxin.

Animals↗
PubMed1980

The interaction of human haemoglobin with allosteric effectors as a model for drug-receptor interactions.

1 The release of bound oxygen from oxyhaemoglobin by allosteric effectors is considered as a model for those drug-receptor interactions where the primary response to agonist binding is the release of a second messenger species. 2 A theory of haemoglobin oxygenation, based on the two-state model of Monod, Wyman & Changeux (1965) is used to predict the relationship between 'pharmacological' response and dose of agonist. This relationship is the same as that derived from classical pharmacological occupancy theory. 3 The potency of an agonist is a weighted average of its affinities for the two conformational states of the receptor. 4 The efficacy of an agonist depends not only upon its binding to one of the two conformational states, but also on its ability to alter the functional properties of that state by lowering the affinity of the state for the second messenger. 5 2,3-Diphosphoglycerate and adenosine triphosphate are approximately equipotent and of similar efficacy, but inositol hexaphosphate is about 500 times more potent and has a higher efficacy.

Adenosine Triphosphate↗
PubMed1978

A quantitative analysis of the effects of 2,3-diphosphoglycerate, adenosine triphosphate and inositol hexaphosphate on the oxygen dissociation curve of human haemoglobin.

1. Oxygen dissociation curves have been measured for human haemoglobin solutions with different concentrations of the allosteric effectors 2,3-diphosphoglycerate, adenosine triphosphate and inositol hexaphosphate. 2. Each effector produces a concentration dependent right shift of the oxygen dissociation curve, but a point is reached where the shift is maximal and increasing the effector concentration has no further effect. 3. Mathematical models based on the Monod, Wyman & Changeux (1965) treatment of allosteric proteins have been fitted to the data. For each compound the simple two-state model and its extension to take account of subunit inequivalence were shown to be inadequate, and a better fit was obtained by allowing the effector to lower the oxygen affinity of the deoxy conformational state as well as binding preferentially to this conformation.

Adenosine Triphosphate↗
PubMedDate not supplied

Contractile effects of vanadate on aorta rings from virgin and pregnant rats.

The present study was undertaken to characterize the contractile effects of vanadate on thoracic aorta rings from virgin and term-pregnant rats. Vanadate caused concentration-dependent contraction in rat aortic rings with an EC50 (concentration producing 50% maximum response) of 0.10 mM. Contractions in response to vanadate were equivalent to the ones measured with 1 microM phenylephrine. The effects of vanadate were not affected by indomethacin (up to 10 microM), an inhibitor of prostanoid cyclooxygenase, but were blocked in a concentration-dependent manner by staurosporine (0.1-1.0 microM), an inhibitor of protein kinase C. Vanadate exhibited a significant decrease of contractile responses in aorta of pregnant as compared to virgin rats. When aortic rings were bathed in presence of different concentrations of vanadate, the concentration-response curve to phenylephrine was shifted to the left, but maximum response was not affected. The potentiation of the contractions to phenylephrine by vanadate was significantly more prominent in aorta of virgin than of pregnant rats. These results suggest that the contractile effect of vanadate on rat aorta is independent of endogenous prostanoids and may be mediated by protein kinase C-dependent pathway. These results also show that the contractile response to vanadate on the rat aorta is impaired during pregnancy.

Animals↗
PubMedDate not supplied

Decreased response to vasopressin in the mesenteric resistance arteries of pregnant rats: effects of nifedipine and Bay K 8644.

OBJECTIVE: The purpose of this study was to investigate the contribution of potential-operated calcium (POC) channels in the mechanisms of the blunted effects of vasoconstrictors on mesenteric resistance arteries during normal pregnancy. METHODS: Mesenteric resistance arteries of virgin and term pregnant rats were set up under optimum passive tension in wire myograph systems. Cumulative concentration-response curves of arginine8-vasopressin (AVP) were measured in the absence and presence of nifedipine or Bay K 8644, a blocker and an activator, respectively, of POC channels. Binding studies were performed on membrane preparations of the mesenteric vascular bed of both groups of rats using saturation with [3H]nitrendipine. RESULTS: The maximal response to AVP was statistically similar in the two groups of arteries. Pregnancy shifted the AVP concentration-response curves to the right. Nifedipine (1 mumol/L) similarly reduced the maximum response to AVP in arteries of both groups, but produced a larger increase in EC50, the concentration inducing 50% maximum response, in resistance arteries of virgin versus pregnant rats. Bay K 8644 did not affect the maximum tension reached with AVP. However, it increased the effects of small concentrations of AVP in arteries of both groups. This was more important in tissues of virgin than pregnant rats. Binding of [3H]nitrendipine to membrane preparations of mesenteric vessels was not modified by pregnancy. CONCLUSION: Our results suggest a reduced functional influence of POC channels in the myotropic effects of AVP on mesenteric resistance arteries in pregnancy. This decreased influence of POC channels may contribute to resistance of the vasculature to vasopressor agents during pregnancy.

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