PubMed Health⌕ Search

Biomedical subjects

L Estañ

Publications and source records attributed to L Estañ.

14 recordsLinked to original sources

Isolated human chorionic vascular reactivity: technical considerations for fresh preparations.

1. Sixty chorionic vascular rings from normal term placentas were immersed in an organ bath for isometric tension recording to study (A) the contractile response to 120 mM of potassium chloride (KCl) after adjustment and equilibration to 1-5 g of passive tension; and (B) the concentration-response curve to KCl after adjustment and equilibration to the optimal passive tension. 2. Adjustment to 4 g of passive tension elicited the maximal (P < 0.007) and the latest (P < 0.006) KCl-induced contraction among arterial rings. Venous rings showed the greatest contraction when adjusted to 3 g, but the differences were not significant except when compared to 1 g of passive tension (P < 0.03). 3. The EC50 for chorionic arteries and veins was 14.2 and 25.7 mM, respectively (P < 0.003). The maximal contraction was already obtained with 40 mM of KCl. 4. Our results suggest that (A) the optimal passive tension for fresh human chorionic arteries is 4 g; (B) chorionic venous reactivity is less influenced by the initial tension; and (C) the optimal concentration of KCl to be used as a contracting agent of these tissues is 40 mM.

Arteries↗

The effects of epinine on arterial blood pressure and regional vascular resistances in anesthetized rats.

1. We carried out experiments in anesthetized rats to study the hemodynamic effects of intravenous injections of epinine. 2. Epinine (1-320 micrograms/kg) produced a biphasic effect on mean arterial blood pressure (n = 30). At doses lower than 40 micrograms/kg, arterial blood pressure decreased (by as much as 21.5 +/- 3.4%), though at higher doses it increased dose dependently (by as much as 73.2 +/- 14.5%). Epinine also produced bradicardia in a dose-dependent manner (by as much as 26.4 +/- 4.9%). Sulpiride (100 micrograms/kg) suppressed the hypotensive effect of epinine but did not change the hypertensive effect. In the presence of prazosin (1,000 micrograms/kg), arterial blood pressure remained significantly decreased at all doses of epinine. Neither sulpiride nor prazosin changed the bradycardic effect of epinine. 3. Prazosin produced a significant decrease in renal vascular resistance. Epinine (5 micrograms/kg) after prazosin reverted the effects of prazosin in renal vascular resistance, without any significant modification in the renal blood flows. However, 20 micrograms/kg epinine increased the renal vascular resistances and, moreover, produced a significant decrease in the blood flows of both kidneys. Neither prazosin nor epinine produced modifications in the intestinal vascular bed. 4. Although epinine possesses significant dopamine and alpha-adrenergic activities that are involved in the biphasic effect of the agent on mean arterial blood pressure in anesthetized rats, in the presence of prazosin, it is not possible to manifest dopaminergic activity involved in the increase in renal or mesenteric blood flow; this may be due to the low tone of the vascular wall induced by the alpha-adrenergic antagonist, though an alpha 2-activity cannot be discarded.

Anesthetics, Intravenous↗

A prospective study of adverse drug reactions as a cause of admission to a paediatric hospital.

1. A total of 512 consecutive paediatric hospital admissions of children 2 years old or less were evaluated to assess the extent and pattern of admission caused by suspected adverse drug reactions (ADRs). the proportion of suspected ADRs related to hospital admissions was 4.3%. 2. The organ-systems most commonly implicated were the central nervous system (40.5%), digestive system (16.7%), and skin and appendages (14.3%). Together, they accounted for 71.5% of admissions attributed to ADRs. The most common clinical manifestations inducing admission were convulsions (4 cases), dizziness (4), vomiting (3), and tremor, fever, itching and apnoea (2 cases each). 3. The four classes of drugs most frequently suspected in admissions due to ADRs were respiratory drugs (35%), anti-infective agents (25%), drugs active on the central nervous system (15%) and drugs used in dermatology (10%). The most common drugs related to ADRs were a combination of chlorpheniramine, diphenhydramine, phenylephrine, guaiphenesin and salicylic acid (4 cases), followed by fenoterol, adrenaline, paracetamol, DTP vaccine and antipolio vaccine (2 cases each). 4. There were no significant differences between children older and younger than 1 year (odds ratio 0.89; 95% CI 0.37-2.17) or between the sexes as regards hospital admittance due to suspected ADRs (odds ratio 1.94; 95% CI 0.72-5.42). 5. The results of this kind of study may be influenced by patterns of drug utilization. Nevertheless, the lack of specific studies of drug effects in young children makes it desirable to carry out pharmacoepidemiological studies in this age group.

Child, Preschool↗

Isolated human colon strips as a pharmacological tool.

The spontaneous activity of isolated human colon strips was studied to obtain homogeneous results with a reproducible model. The strips of macroscopically normal appearance were mounted in an organ bath containing Krebs solution at 32 degrees C or Tyrode solution at 37 degrees C. Mechanical activity was recorded by an isometric transducer. Spontaneous motility did not occur in all preparations. Moreover, when observed, it could not always be evaluated. The percentage of strips with spontaneous activity was lower with Tyrode solution than with Krebs solution (65 vs. 81%). KC1 did not induce a plateau contraction. Acetylcholine induced concentration-dependent contractions, with a significantly different pD2: 4.43 +/- 0.39 and 5.59 +/- 0.16 for Krebs and Tyrode, respectively. Isoprenaline abolished spontaneous motility in Krebs solution. Only 20% of specimens presented evaluable motility. Krebs solution may be the best conditions for studying the effects of drugs on spontaneous motility, while Tyrode solution can be used to investigate the effects of contractile agents.

Acetylcholine↗

Effect of histamine on the longitudinal and circular muscle of the oestrogen dominated rat uterus.

The response of the longitudinal and circular myometrial strips to histamine was studied in oestrogen-treated rats. Histamine produced a dose-related inhibitory response in KCl-contracted longitudinal and circular uterine strips. Histamine was equipotent in producing the relaxant response but the maximal effect achieved in the longitudinal muscle was higher than the circular one. Ranitidine antagonized the histamine-induced relaxation with a similar dose ratio in both longitudinal and circular strips. Clemizole and reserpine treatment did not produce any modification of the dose-response curve to histamine. In the longitudinal and circular strips which were not preconstricted by KCl, neither histamine nor 2-pyridylethylamine, even in strips pretreated with ranitidine, produced any effect when added to the organ bath. Our results show that the response of histamine in both longitudinal and circular uterine layers of the oestrogen-treated rats are mediated exclusively by histamine H2-receptors.

Animals↗

Response to dopamine agonists of the rat isolated uterus.

1. Quinpirole did not produce any effect in isolated uterus from oestrogenized rats even when it is contracted by KCl (37 mM). 2. Fenoldopam produced a relaxant effect on rat isolated uterus contracted by KCl which was not significantly modified by SCH 23390. 3. Reserpine decreased the effect of the lowest doses of fenoldopam. In reserpinized rats, propranolol (10(-9), 10(-8), 10(-7) M) antagonized the effect of the lowest doses of fenoldopam and neither SCH 23390, sulpiride nor ranitidine modified the effect of fenoldopam. 4. The results confirm our previous finding that DA1-receptors are not functional in our preparation. The effect of fenoldopam was partially due to a catecholamine-releasing action.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Effect of histamine and histamine analogues on human isolated myometrial strips.

1. The effect of histamine and histamine H1- and H2-receptor agonists on isolated myometrium strips of premenopausal women has been examined. The effect of acetylcholine was also determined. 2. Histamine, 2-pyridylethylamine, 4-methylhistamine and acetylcholine, but not dimaprit, produced a concentration-related contractile response in human isolated myometrial strips. Histamine also produced a further contraction in human isolated myometrial strips precontracted with KCl (55 mM). 3. The contractile response to histamine was antagonized by the histamine H1-receptor antagonist, clemizole (0.1 microM) but was potentiated by the histamine H2-receptor antagonist, ranitidine (10 microM). Clemizole (0.1 nM to 10 nM) competitively antagonized the contractile effect of 2-pyridylethylamine (- log KB = 10.5 +/- 0.5). The concentration-response curve for acetylcholine was displaced to the right by atropine 0.1 microM. 4. Atropine (0.1 microM), propranolol (0.1 microM), prazosin (0.1 microM) and indomethacin (1 microM) failed to modify the contractile response to histamine. 5. In human isolated myometrial strips precontracted with KCl (55 mM), clemizole at 1 microM completely abolished the contractile response to histamine and revealed a concentration-dependent relaxation. Dimaprit alone and 4-methylhistamine (in the presence of clemizole), produced concentration-related relaxation with a magnitude similar to that in response to histamine. The relaxant response to dimaprit was antagonized by ranitidine. 6. It is concluded that human isolated uterine strips possess histamine H1- and H2-receptors: the former mediating contraction and the latter relaxation. The predominant response to histamine in this tissue is contraction.

Acetylcholine↗

Effects of methoxamine on spontaneous uterine activity and blood flow of the rat uterus 'in vivo'.

The vascular (blood pressure, heart rate and peripheral blood flow) and uterine (spontaneous motility) responses to intravenous methoxamine were studied in anaesthetized rats pre-treated with diethylstilboestrol. Methoxamine produced an increase (0.5-2 mg/kg) or did not modify (0.01 and 3 mg/kg) spontaneous uterine motility. The alpha 1-agonist also induced a hypertensive effect (0.1-3 mg/kg) accompanied by bradycardia at the highest doses, and a decrease in blood flow significantly greater in intestinal than uterine tissues. These effects were abolished by prazosin. The uterine action of methoxamine in vivo appears to result from the balance between myometrial alpha 1-excitatory effect and vascular alpha 1-vasoconstriction which induced uterine inhibition. The oestrogens appear to protect the alpha 1-mediated vasoconstriction.

Animals↗

Studies of the spontaneous motility and the effect of histamine on isolated myometrial strips of the nonpregnant human uterus: the influence of various uterine abnormalities.

We investigated the spontaneous uterine activity of isolated corpus uteri myometrial strips from 30 patients with nonpathologic myometrium, 26 patients with uterine myoma, 23 patients with uterine adenomyosis, and three patients with uterine malignancy. We also investigated the influence of these conditions on the response of the uterus to histamine. The results show the same qualitative cyclic changes of the spontaneous motility of isolated myometrial strips throughout the menstrual cycle in all the abnormalities studied. These changes are characterized by a low amplitude and high frequency of spontaneous contractions in the proliferative phase and lower frequency with higher amplitude of contractions in the secretory phase. The isolated strips from patients with myomas present the highest spontaneous activity in reproductive age and preclimacteric women, but not in menopausal women. Histamine produced concentration-related contractions that are not significantly different in all the myometrial strips studied.

Female↗

Study on the histamine-like activity of guanfacine.

The effects of guanfacine have been studied on guinea-pig isolated atria and diethylstilboestrol-treated rat isolated uterus to determine whether it possesses histamine-like activity. Guanfacine produced a concentration-dependent negative chronotropic effect which was not modified by ranitidine (0.1 microM). In rat isolated uterus contracted by KCl, clonidine (5-5000 microM) produced concentration-dependent relaxation which was blocked by ranitidine (0.1 microM), but guanfacine only produced relaxation at high concentrations (100-1000 microM), and this was not affected by ranitidine (0.1 microM). It is concluded that guanfacine, unlike clonidine, does not produce effects due to activation of H2-receptors in either guinea-pig atria or rat uterus.

Adrenergic alpha-Agonists↗

Relaxant effect of dopamine on the isolated rat uterus.

The effect of dopamine was studied on the isolated uterus of diethylstilboestrol-treated rats. Dopamine, at concentrations (10(7)-10(-4) M) produced a concentration-dependent relaxation in the K+-depolarized rat uterus. On a molar basis, dopamine was about 500 times less potent than adrenaline in relaxing the uterus, the maximum degree of relaxation obtained with both drugs was the same. Pretreatment of the rats with reserpine (5 mg/kg) did not produce any modification of the dose-response curve to dopamine. Similarly, cocaine (3 x 10(-6) M) failed to modify the relaxant effect of dopamine. The dopamine induced relaxation was inhibited by propranolol (10(-9)-10(-7) M) in a dose-dependent manner. Prazosin (10(-7) M), SCH 23390 (10(-7) M) and sulpiride (10(-7) M) did not affect the dopamine dose-response curve. In the isolated rat uterus which was not preconstricted by KCl neither dopamine nor adrenaline produced any effect when added to the organ bath. This lack of response to both catecholamines was present even in tissues pretreated with propranolol or sulpiride. It is concluded that dopamine produced a concentration-dependent relaxation of the uterus from diethylstilboestrol-treated rats by direct activation of beta-adrenoceptors. There was no evidence for indirect action (catecholamine release and neuronal uptake mechanisms) and specific dopamine receptor mediated relaxation and alpha-adrenoceptor mediated contractions have not been found in this preparation.

Animals↗

Antihistaminic and anticholinergic activities of mequitazine in comparison with clemizole.

The antihistamine and anticholinergic properties of mequitazine have been investigated and compared with those of clemizole. Both mequitazine and clemizole antagonized the effect of histamine in guinea-pig ileum competitively, the pA2 values calculated by Schild plot were 9.95 +/- 0.44 for mequitazine and 10.54 +/- 0.44 for clemizole. Mequitazine at 10(-7) M produced a parallel shift of the dose-response curve to acetylcholine in the rat duodenum, clemizole and the lower doses of mequitazine failed to modify the effect of acetylcholine. The potency of mequitazine and clemizole as H1-histamine blockers is similar, but only mequitazine at highest concentration used showed anticholinergic activity.

Acetylcholine↗

Effect of domperidone on the contractility of isolated guinea-pig atria.

This study was undertaken to investigate whether or not dopamine receptors are responsible for the cardiac action of domperidone and to gain a better understanding of the mechanism of the cardiac effects of this compound. In isolated electrically driven guinea-pig atria, domperidone (0.1-30 microM) produced a negative inotropic effect (-56.7 +/- 4.9% at 30 microM) and at a concentration of 0.1 microM significantly decreased the positive inotropic response to histamine (0.5-271 microM). In spontaneously beating guinea-pig atria, domperidone failed to modify the chronotropic responses elicited by dopamine and noradrenaline. In the isolated guinea-pig ileum, domperidone alone did not produce any effect, but produced a right-ward displacement of the contractile dose-response curve to histamine. At concentrations of 0.01, 0.1 and 1 microM, domperidone also depressed the maximum response to histamine. The results obtained suggest that the negative inotropic effect of domperidone is not due to dopamine or adrenergic receptor antagonism. This cardiac effect of domperidone can be partially explained by its influence on the effects of histamine acting on H1-receptors, although other mechanisms may be involved.

Animals↗

Effect of methoxamine on spontaneous motility of the isolated rat uterus.

In the present study the effect of methoxamine and its modification by several adrenergic antagonists is described in the isolated oestrogenized rat uterus. Methoxamine produced a dose-related increase in uterine activity, prazosin produced a rightward displacement of the dose-response curve of methoxamine reaching the same maximal effect. Yohimbine abolished the contractile response to methoxamine. propranolol or reserpine failed to modify the effect of methoxamine. Pretreatment with reserpine abolished the inhibitory effect of yohimbine. These results suggest the presence of excitatory alpha-adrenoceptors in the rat uterus.

Adrenergic alpha-Agonists↗