Biomedical subjects

A Hidalgo

Publications and source records attributed to A Hidalgo.

At least 109 records · Page 6Linked to original sources

PubMed1994

Genomic and non-genomic effects of steroidal drugs on smooth muscle contraction in vitro.

The effect of steroidal drugs on KCl (60 mM)-induced tonic contraction in in vitro rat uterus has been assayed. Ouabain had no effect and aldosterone only relaxed the KCl contraction up to 27 +/- 7.3%. However, estradiol, testosterone, progesterone, cortisol and alphaxalone relaxed the contraction in a dose-dependent way, and CaCl2 (0.1 to 6 mM) counteracted this effect. Cycloheximide (1 and 10 micrograms/ml) did not modify the effect of progesterone, testosterone or alphaxalone. Cycloheximide, but not actinomycin D (5 micrograms/ml), reduced the effect of cortisol. Both cycloheximide and actinomycin D shifted righward the relaxing effect of estradiol. This suggests that the steroidal relaxing effect in smooth muscle is preferably non-genomic and at plasma membrane level. However, cortisol and estradiol also act at intracellular levels and induce transcriptional (estradiol) or non-transcriptional (cortisol) effects.

Animals↗

PubMed1994

Progesterone and pregnanolone derivatives relaxing effect on smooth muscle.

1. The effect of gestagens, 5 alpha-hydroxyprogesterone (10(-6) x 10(-5) M), 5 beta-hydroxyprogesterone (10(-6)-3 x 10(-5) M), progesterone (6 x 10(-6)-10(-4) M), pregnanolone (10(-6)-10(-5) M), allopregnanolone (10(-6)-10(-4) M) and epipregnanolone (10(-6)-6 x 10(-5) M) on rat uterine contractions induced by KCl (60 mM), has been assayed. 2. All drugs assayed relaxed the tonic-contraction induced by KCl in a concentration-dependent way. The respectives IC50 were 31.3 +/- 4.1 x 10(-6) M (progesterone), 8.9 +/- 0.8 x 10(-6) M (5 alpha-hydroxyprogesterone), 3.8 +/- 0.3 x 10(-6) M (5 beta-hydroxyprogesterone), 3.1 +/- 0.1 x 10(-6) M (pregnanolone), 21.2 +/- 3.1 x 10(-6) M (allopregnanolone) and 6.3 +/- 1.3 x 10(-6) M (epipregnanolone). This relaxing effect was partially or totally counteracted by CaCl2 (1-10 mM) 3. Cycloheximide (10 micrograms/ml) significantly shifted to the right the effect of allopregnanolone but not the effect of the other drugs. Actinomycin D (5 micrograms/ml) did not modify the effect of allopregnanolone. 4. Our results suggest that the relaxing effect of gestagens in the rat uterus could be related to inhibition on calcium influx and mainly occur through non-genomic mechanisms.

Animals↗

PubMed1994

Gender and test dependence of a type of kappa mediated stress induced analgesia in mice.

1. In male mice, 80 inescapable footshocks (S-80) induce analgesic responses measured by the tail flick test that are blocked by naloxone and the kappa opioid antagonist, nor-binaltorphimine. We now study the nociceptive responses, induced after this particular stress, measured by the writhing test, the tail immersion test and a high intensity tail immersion test both in male and female mice. 2. In stressed males, analgesic responses are seen in all the nociceptive tests. Naloxone (10 mg/kg) does not prevent them. 3. In stressed females, in contrast with males, no analgesia is produced in the tail flick test. The writhing test and the tail immersion test registered analgesic responses that were not prevented by naloxone (10 mg/kg). 4. We conclude that only the antinociceptive kappa opioid mediated component of the stress we study is strongly dependent on gender, in contrast to other types of analgesia triggered by the same stress.

Analgesia↗

PubMed1994

Influences of age and sex on endothelium-dependent vascular responses and arterial blood pressure in the rat.

1. Vascular reactivity related to age and sex on two endothelium-dependent effects in isolated rat aorta (acetylcholine-induced relaxation and modulation of noradrenaline response) and blood pressure decreases by acetylcholine administration were studied. Group of male Wistar rats aged 2, 4, 8, 16 and 24 months plus female rats of 4 months were used. 2. Blood pressure was measured by using a standard tail-cuff technique. Acetylcholine in vivo administration (0.002 mg/kg i.v.) significantly reduced diastolic pressures in the 2 month old males and 4 month old females, but not in other age groups. 3. Isolated helical strips of rat aorta were used to determine the endothelium-dependent reactivity. The maximal relaxation from different groups of male rats induced by acetylcholine was: 100% in those of 2 months; 53.2 +/- 6.0% in those of 4 months; 61.8 +/- 6.1% in those of 8 months; 57.6 +/- 5.0% in those of 16 months and 31.0 +/- 4.9% in those of 24 months. Concentration-response curves to noradrenaline were significantly greater only when endothelial cells were removed from aorta strips of 2 month old rats. In aorta strips with endothelium the maximal contraction to noradrenaline was significantly greater in 2 month old rats when compared with the other groups and smaller in aorta strips from 24 month old rats. 4. These results suggest that the endothelium-dependent effects studied and the noradrenaline-induced contraction decreased according to the age of the rats.

Acetylcholine↗

PubMed1993

Involvement of spinal kappa opioid receptors in a type of footshock induced analgesia in mice.

We have studied the effects of several opioid antagonists on a type of footshock stress-induced analgesia (FSIA) measured by the tail-flick test in male mice. Naloxone injected either subcutaneously (0.1-10 mg/kg) or intrathecally (1-20 micrograms) antagonized FSIA at higher doses than those that blocked a similar degree of analgesia induced by morphine. Intracerebroventricular (i.c.v.) naloxone (1-20 micrograms) did not modify the FSIA while antagonizing the i.c.v. morphine-induced analgesia. As a consequence, the antagonism of the FSIA by naloxone probably occurs at the level of the spinal cord and through receptors different than mu. The delta selective antagonist naltrindole (0.1-3 mg/kg s.c.) did not antagonize the analgesic effects of the stress. Nor-binaltorphimine, a kappa selective antagonist, blocked the FSIA when administered systemically (1-4 mg/kg i.p.) or locally (0.1-1 microgram i.t.). These results strongly suggest that spinal kappa opioid receptors are responsible for this type of endogenous analgesia.

Analgesia↗

PubMed1993

Effects of androgens on isolated rat uterus.

The 5 alpha- and 5 beta-dihydrotestosterone (DHT) androgens relax KCl-induced tonic contraction in rat uterus, in a dose-dependent way. The 5 alpha and 5 beta-DHT relaxing effect is counteracted by CaCl2 (0.1-10 mM). The 5 alpha-DHT, but not the 5 beta-DHT, effect was reduced by cycloheximide (10 micrograms/ml) and by actinomycin D (5 micrograms/ml). Flutamide at 10(-6) M shifted the effect of 5 alpha-DHT to the right. However, other doses of flutamide or cyproterone acetate did not modify the effect of both androgens. We suggest a non-genomic effect of 5 alpha-DHT and 5 beta-DHT in rat uterus contraction but that intracellular and genomic actions play a part in the relaxing effect of 5 alpha-DHT.

Animals↗

PubMed1993

Opioid footshock-induced analgesia in mice acutely falls by stress prolongation.

The application of 80 footshocks (S-80) to mice induces a decrease in nociceptive responses as measured by the tail-flick test, which is opioid mediated as well as prevented by naloxone (10 mg/kg, SC). When the stress is prolonged up to 240 shocks (S-240) (i.e., from 6 min 40 s to 20 min), no analgesia can be seen immediately after the stress. We have examined the two most obvious possibilities, but they do not seem to be responsible for this fact. When morphine (1-5 mg/kg IP) is injected in the S-240 situation, a potentiation of its analgesic effects is seen, so that a desensitization of mu opioid receptors is unlikely. On the other hand, although cortisol (3-30 mg/kg IP) inhibits the analgesic response to S-80, metyrapone (40 and 80 mg/kg IP) and cortexolone (3-18 mg/kg IP) do not cause S-240 to be analgesic. Thus, an increase of endogenous glucocorticoids released during the long-duration stress does not seem responsible for the lack of analgesia after S-240.

Animals↗

PubMed1993

Estrogen and antiestrogen non-genomic effect in rat uterus contraction in calcium-free solution.

1. The effects of estrogens estradiol (E2, 10(-6)-10(-4) M) and diethylstilbestrol (DES, 10(-6)-10(-4) M) and the antiestrogens nafoxidine (N, 10(-6)-10(-4) M), tamoxifen (T, 10(-6)-6 x 10(-4) M), tamoxifen ethyl bromide (TEB, 10(-4) M) and ICI 164,384 (ICI, 10(-5) M) on tonic contractions induced by oxytocin (2 x 10(-8) M) or vanadate (3 x 10(-4) M) in rat uterus incubated in calcium-free EDTA treated solution have been assayed. 2. E2 and DES relaxed the tonic contraction induced by oxytocin in a dose dependent way (EC50: 1.11 +/- 0.01 x 10(-4) M and 1.5 +/- 0.07 x 10(-5) M). The vanadate-induced contraction only was relaxed with DES (57.62 +/- 2.38% at 10(-3) M). 3. The effect of DES on oxytocin contraction was unmodified by the protein synthesis inhibitor cycloheximide (10 micrograms/ml) and by the cyclooxygenase inhibitor indomethacin (3 x 10(-6) M), but enhanced by the intracellular calcium release inhibitor TMB-8 (10(-5) M). The antiestrogen tamoxifen (3 x 10(-5) M) promotes the relaxing effect of DES. 4. The antiestrogens N, and T, but not ICI, relaxed the oxytocin-induced contraction (EC50: 4.51 +/- 0.43 x 10(-5) M and 2.27 +/- 0.05 x 10(-4) M). TEB (10(-4) M) produces a relaxation of 74.5 +/- 2.11%. The vanadate contraction is also relaxed by T (EC50: 6.03 +/- 0.04 x 10(-4) M). 5. The effect of T on oxytocin contraction was unmodified with cycloheximide or TMB-8 but decreased with indomethacin.

Animals↗

PubMed1993

Effects of phorbol 12,13-dibutyrate and H-7 in extravascular smooth muscle contraction.

The effect of the activator, phorbol 12,13-dibutyrate (PDB), and the inhibitor, H-7, of protein kinase C (PKC) has been assayed in rat uterus. PDB increases the amplitude of spontaneous contractions of rat uterus and this effect does not occur in the presence of H-7 or nifedipine. PDB did not modify the KCl-induced tonic contraction but H-7 relaxed it, in a concentration-dependent way. PDB inhibited the contraction induced by oxytocin in rat uterus incubated in Ca-free solution and relaxed the tonic contraction induced by oxytocin in this medium. The relaxing effect of PDB on oxytocin-induced contraction was not modified by H-7. Thus H-7 relaxed, in a concentration-dependent way, the tonic contractions induced by oxytocin and vanadate in the rat uterus incubated in Ca-free medium. Our results suggest a dual effect of PDB related to calcium, and a direct and PKC-independent inhibitory effect of H-7.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1993

Regulation of wingless transcription in the Drosophila embryo.

The segment polarity gene wingless (wg) is expressed in a complex pattern during embryogenesis suggesting that it plays multiple roles in the development of the embryo. The best characterized of these is its role in cell pattening in each parasegment, a process that requires the activity of other segment polarity genes including patched (ptc) and hedgehog (hh). Here we present further evidence that ptc and hh encode components of a signal transduction pathway that regulate the expression of wg transcription following its activation by pair-rule genes. We also show that most other aspects of wg expression are independent of this regulatory network.

Animals↗

PubMed1992

Mediators involved in the rat uterus contraction in calcium-free solution.

1. The effect of (Na+ + K+)-ATPase inhibitor ouabain (10(-5)-3 x 10(-4) M), and the (Ca2+ + Mg2+)-ATPase inhibitors vanadate (6 x 10(-6)-6 x 10(-4) M), oxytocin (2 x 10(-9)-4 x 10(-8) M, and prostaglandin F2 alpha (PGF2 alpha, 10(-7)-6 x 10(-6) M) were assayed on rat uterus incubated in Ca-free medium. 2. Vanadate, oxytocin and PGF2 alpha, but not ouabain, induced contractions in a dose-dependent way (ED50: 7.5 +/- 0.03 x 10(-5) M; 6.5 +/- 0.064 x 10(-9) M and 3.8 +/- 0.085 x 10(-7) M). 3. Vanadate (3 x 10(-4) M) and oxytocin (OT, 10 mU/ml = 2 x 10(-8) M)-induced tonic contraction were not modified by nifedipine (10(-10)-10(-6) M), monensin (10(-5)-3 x 10(-4) M) or amiloride (10(-5)-10(-3) M). 4. The intracellular calcium release inhibitors TMB-8 (10(-6)-10(-4) M) and dantrolene (3 x 10(-6)-10(-4) M), and the prostaglandin release inhibitor indomethacin (3 x 10(-8)-6 x 10(-5) M) relaxed the vanadate and OT-induced tonic contractions. 5. The calmodulin inhibitors trifluoperazine (3 x 10(-5)-3 x 10(-4) M), bepridil (10(-8)-3 x 10(-4) M), calmidazolium (10(-7)-10(-4) M) and W-7 (10(-7)-10(-5) M) also relaxed the vanadate and OT-induced tonic contractions. 6. Our results suggest that oxytocin and vanadate-induced contractions on rat uterus in Ca-free medium could be produced by release of prostaglandins and intracellular calcium, and mediated by calmodulin.

Animals↗

PubMed1992

Differential effect of calcium and Bay K 8644 on the inhibitory action of estrogens in the rat uterus.

1. The effects of the estrogens estradiol (E2, 10(-7) to 3 x 10(-5) M) and diethylstilbestrol (DES, 10(-7) to 3 x 10(-6) M) on tonic contractions of the rat uterus induced by KCl and CaCl2 have been studied. 2. E2 and DES relaxed, in a dose-dependent way, the tonic contraction induced by KCl (60 mM) (IC50: 5.16 +/- 1.49 x 10(-6) and 4.51 +/- 0.03 x 10(-7) M); the tonic contraction induced by CaCl2 (3 mM) in the rat uterus incubated in depolarizing Krebs (127 mM of K+) have also been relaxed (IC50: 8.6 +/- 0.03 x 10(-7) and 2.56 +/- 0.07 x 10 M) by both drugs. 3. The CaCl2 (0.1 to 10 mM) counteracted the relaxing effect of E2 and DES, respectively, up to 28.13 +/- 10.2% and 34.71 +/- 11.5%, on KCl-induced contractions, and up to 126.36 +/- 19.35% and 95.8 +/- 16.3% on CaCl2-induced contractions. 4. Bay K 8644 (10(-10) to 10(-6) M) reversed the relaxing effect of E2 and DES, respectively, up to 42.49 +/- 2.28% and 43.31 +/- 3.59% on KCl-induced contractions, and up to 21.73 +/- 4.16% and 75.97 +/- 9.63% on CaCl2-induced contractions. 5. Propranolol (10(-6) M) did not modify the relaxing effect of E2 or DES on CaCl2-induced contractions.

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

PubMed1992

Effects of antiandrogens and progesterone on isolated rat uterus.

1. The effect of progesterone (P, 6 x 10(-6)-6 x 10(-5) M) and the antiandrogens cyproterone acetate (CPA, 10(-7)-10(-5) M), flutamide (F, 10(-6)-6 x 10(-5) M) and spironolactone (S, 10(-6)-6 x 10(-5) M) on the KCl-induced tonic contraction of the isolated rat uterus have been assayed. 2. The antiandrogens relaxed, in a dose-dependent way, the KCl-induced contraction (EC50, 2.804 +/- 0.506 x 10(-6); 1.671 +/- 0.308 x 10(-5); and 3.042 +/- 0.14 x 10(-5) M, respectively for CPA, S and F). P also relaxed the KCl-induced contraction (EC50, 2.436 +/- 0.524 x 10(-5) M). 3. CaCl2 (0.1-10 mM) counteracted the relaxing effect of CPA, S, F, and P, respectively, up to 100, 80.63, 60.66 and 90.57%. 4. The 17-OH-progesterone derivative CPA, but not S or F, reduces at small doses (6 x 10(-8) M), but not at higher concentrations (6 x 10(-7)-6 x 10(-6) M), the relaxing effect of progesterone.

Androgen Antagonists↗

PubMed1992

Effects of androgens and antiandrogens on the inotropism induced by ouabain and isoproterenol on the left atrium of the rat in vitro.

1. The effect of androgens 5 beta- and 5 alpha-dihydrotestosterone (DHT, 10(-9) M), and the antiandrogens cyproterone acetate (CPA, 10(-8)-10(-6) M), chlormadinone acetate (CMA, 10(-8)-10(-6) M), medroxyprogesterone acetate (MPA, 10(-8)-10(-6) M), spironolactone (SPI, 10(-5) M), flutamide (F, 10(-5) M) and cimetidine (C, 10(-5) M), on inotropic positive effect induced by ouabain (10(-8)-10(-5) M) and isoproterenol (10(-8)-10(-6) M), on electrically stimulated left atria of rat, has been assayed. 2. Ouabain (10(-6) M) did not modify the inotropic effect of isoproterenol (10(-8)-10(-6) M). 3. The androgens 5 beta- and 5 alpha-DHT (10(-9) M) and the antiandrogens SPI (10(-6) M), F (10(-5) M) and C (10(-5) M) inhibit the inotropic effect of ouabain and isoproterenol on electrically stimulated left atria of the rat. 4. The antiandrogens CPA, MPA and CMA to 10(-7) M, inhibit the inotropic effect of ouabain. The CPA (10(-8)-10(-6) M) inhibit, in a dose-dependent way the positive inotropic effect of isoproterenol. MPA and CMA (10(-8)-10(-6) M) also inhibit the inotropic effect isoproterenol but the inhibitory effect is greater with 10(-8) M than 10(-6) M of both drugs. 5. Taken together, our results suggest that steroidal hormones could modulate the cardiac contractility through interference with Na-pump in a non-digitalic site and/or with intracellular mediators in left atrium.

Androgen Antagonists↗

PubMed1992

Effects of nonsteroidal antiestrogens in the in vitro rat uterus.

We have studied the effect of nonsteroidal antiestrogens on rat uterine contractions induced by oxytocin (8 nmol/l), methacholine (10 mumol/l), prostaglandin F2 alpha (1 mumol/l), KCl (60 mmol/l) and CaCl2 (6 mmol/l). In a concentration-dependent way, the antiestrogens tamoxifen, clomiphene, nafoxidine and ethamoxytriphetol inhibited the amplitude and frequency of the oxytocin-induced contractions and the contraction produced by CaCl2. At a concentration of 30 mumol/l the four drugs inhibited the contractions induced by methacholine and prostaglandin F2 alpha. They also relaxed the tonic contraction to KCl in a concentration-dependent way. This action was partially counteracted by CaCl2 (0.1-10 mmol/l). Bay k 8644 (0.3 nmol/l to 3 mumol/l) only partially reversed the inhibition by ethamoxytriphetol (0.1 mmol/l) of CaCl2 (6 mmol/l)-induced contractions. The steroidal antiestrogen, ICI 164,384, which lacks agonist activity, had an inhibitory effect (44 +/- 4%, n = 7) on KCl-induced contractions only at a concentration of 0.1 mmol/l. However, the quaternary analogue of tamoxifen (tamoxifen ethyl bromide) produced 86 +/- 3% relaxation of the KCl-induced contracture (IC50 1.52 +/- 0.1 mumol/l, n = 10) and this effect was counteracted by addition of CaCl2. Taken together the results indicate that the inhibitory effects of nonsteroidal antiestrogens on rat uterine contractions could be mediated by an action to block Ca2+ entry through an agonist action on extracellular estrogen receptors.

Animals↗

PubMed1992

Blood types in cattle of Iberian ancestry and in Holsteins at various altitudes.

Gene frequencies of RBC antigens were determined in Holsteins and Colombian (criollas) cattle living at 3,000 m, and in cattle descended from fighting bulls (Vacas de lidia) living at 2,500 m. These frequencies were compared with those of Holsteins, cattle native to Florida (scrub cattle), longhorns, and native cattle from Brazil (caracu cattle) living at sea level. The criollas, Vacas de lidia, scrub cows, longhorns, and caracu are descendants of original Iberian stock introduced to the Americas. We found that despite common ancestry (scrub cattle, long-horns, criollas, and caracu), genetic differences may have been derived through years of demographic isolation. The most remarkable blood-group differences were found in the high prevalence of the B system phenogroup (heritable group of antigenic factors) BQA'G'34 in the Vacas de lidia, and of the S system phenogroup U1H' in these cattle and in caracu. Furthermore, the gene frequencies differed in the Holsteins maintained at moderately high altitude (descended from Holsteins kept at sea level), and may have been reflective of the need to adapt to moderately high altitude and chronic hypoxemic conditions. Blood group polymorphism was found in all groups of cattle, although it was reduced in the Vacas de lidia, possibly because their breeding has been carefully controlled and they appear to be highly inbred.

Altitude↗

PubMed1992

Blood biochemical characteristics of cattle at sea level and at moderately high altitude (3,000 m).

We investigated the biochemical composition of blood from Holstein cows, native breed (criollas), and cows descended from fighting bulls (Vacas de lidia) raised at an altitude of 3,000 m (moderately high altitude, MHA), and compared the results with those from Holsteins and cows of similar genetic ancestry as the criollas (scrub cows), both raised at sea level (SL), to determine blood biochemical values characteristic of adaptation to high altitude. Only potassium and calcium concentrations were similar among groups. Glucose concentration was lower in MHA cows, with the exception of Vacas de lidia. Serum bicarbonate concentration was lower in MHA cows; this finding can be explained by hyperventilation in the hypoxic environment. Serum magnesium concentration was lower in SL and MHA Holsteins than in other groups. Serum phosphate concentration was lower in scrub cows, MHA Holsteins, and criollas than in other groups. Cholesterol concentrations were lower in SL Holsteins, whereas triglycerides were higher in scrub cows and MHA Vacas de lidia. Concentration of high-density lipoprotein was significantly greater in Vacas de lidia and less in MHA criollas than in the other groups. Uric acid and total protein were higher in MHA groups. Using radioimmunoassay for human proteins, thyroxine-binding globulin was undetectable. Total and free thyroxine and free triiodothyronine were higher in scrub cows, followed by Vacas de lidia; lower values were detected in SL and MHA Holsteins and MHA criollas.

Altitude↗

PubMed1992

Influence of mechanical endothelium removal techniques and conservation conditions on rat aorta responses.

Endothelial denudation of aortas induces a lack of relaxation to acetylcholine and enhancement of response to noradrenaline. These modified responses have been studied in rat aorta by using different techniques for mechanical removal of the endothelial layer and maintenance conditions. Rubbing the artery with cotton inside the organ bath preserves the enhancement of response to noradrenaline, and this effect is not present by rubbing the aortas with filter paper outside the organ bath. Both techniques abolished the relaxant response to acetylcholine. The endothelium dependent effects are not observed by conservation of the artery at room temperature during 1 h. The relaxant response to acetylcholine after this period is approximately 29% of the control. These effects were preserved when the conservation temperature was maintained at 4 degrees C and/or the solution was being bubbled with oxygen.

Acetylcholine↗