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J M Saavedra

Publications and source records attributed to J M Saavedra.

At least 73 records · Page 4Linked to original sources
PubMed1995

Sympathetic innervation modulates the expression of angiotensin II receptors in embryonic rat heart grafted in oculo.

Angiotensin II acts as a cardiac growth factor, and causes both inotropic and chronotropic changes within the heart. In the present study, we used an in oculo model system to examine the effects of sympathetic innervation on the density of cardiac angiotensin II receptors. Quantitative autoradiography was used to determine the density of angiotensin II receptors in embryonic rat hearts grafted into either sympathetically innervated or sympathetically denervated eye chambers of adult host rats. The density of specific binding to angiotensin II receptors was nearly three-fold higher in sympathetically non-innervated compared to sympathetically innervated heart grafts (30.8 +/- 4.2 v 11.5 +/- 3.2 fmol/mg protein). Specific binding to angiotensin II receptors in heart grafts was displaced by addition of the AT1 receptor antagonist losartan, but not by addition of the AT2 receptor competitor PD 123177. Thus, only AT1 receptors were present in sympathetically innervated and sympathetically non-innervated embryonic rat hearts grafted in oculo. We conclude that changes in sympathetic innervation caused changes in the density of cardiac angiotensin II receptors in the present study. Our results may have implications for growth and function not only during cardiac development, but also during cardiac disease.

Age Factors↗
PubMed1995

Kidney angiotensin II receptors and converting enzyme in neonatal and adult Wistar-Kyoto and spontaneously hypertensive rats.

The aim of the present study was to correlate the development of the renin angiotensin system (RAS) in the kidney of the rat with the development of genetic hypertension. Immature (1-week-old) and adult (12-week-old) normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive kidney rats (SHR) were used for quantification of angiotensin II (ANG II) receptors and angiotensin converting enzyme (ACE) binding sites using quantitative autoradiography. In both neonatal and adult animals of either strain, ANG II receptors were of AT1 subtype. In all kidney areas of 1-week-old rats. ANG II receptor density was higher in SHR than WKY. Binding density increased with age in WKY rats; thus, in the glomeruli and the outer stripe of the outer medulla of 12-week-old WKY, binding was significantly higher than that present in age-matched SHR. [125I]351A binding to ACE was highest in the outer medulla and not detectable in glomeruli. In 1-week-old rats, binding to ACE was higher in WKY than in SHR strain. No differences in ACE binding were found between adult SHR and WKY rats, with the exception of the inner stripe of the outer medulla, where no binding was detected in SHR. Our results support the hypothesis that the RAS in kidney is developmentally regulated and is involved in the development and maintenance of genetic hypertension in SHR.

Age Factors↗
PubMed1995

Characterization of endothelinA receptors in cerebral and peripheral arteries of the rat.

We have characterized and quantified endothelin receptors in rat brain (anterior cerebral) and peripheral (aorta, carotid, and caudal) arteries, with the use of [125I]endothelin and quantitative autoradiography. Endothelin binding was saturable, of high affinity, and totally displaced by the selective endothelin ETA antagonist BQ 123. A single class of ETA receptors is located in the medial layer of peripheral and cerebral arteries, and its quantification by autoradiography allows study of their regulation and function.

Animals↗
PubMed1995

Angiotensin II receptor subtypes and phosphoinositide hydrolysis in rat adrenal medulla.

Angiotensin II (ANG) receptor subtypes were characterized by quantitative autoradiography after incubation with the ANG agonist [124I]Sar1-ANG in rat adrenal medulla. ANG receptors are highly localized in adrenal medulla. Specific binding was displaced by 4% and by 95% with the AT, receptor blocker losartan and the AT2 receptor competitor CGP 42112A, respectively. Analysis of competition curves indicated relative binding potencies for the AT2 population of CGP 42112A>PD 123319> PD 123177. ANG stimulated +-nositol phosphate formation in a dose-dependent manner in rat adrenal medulla. Losartan at concentrations of 10(-9) to 10(-5) M antagonized the effect of ANG, whereas PD 123177 or PD 123319 had no antagonistic action. However, at a higher concentration (10(-5) M) PD 123177 or PD 123319 potentiated the effect of ANG on InsP1-accumulation. In the presence of PD 123319 (10(-5) M) ANG dose-response curve was shifted to the left with no change in the maximal effect. This affect was blocked by the addition of losartan (10(-5) M). On the contrary, the addition of CGP 42112A (10(-6) M) inhibited ANG-induced increase in InsP1-accumulation. On the other hand, ANG and CGP 42112A reduced basal cyclic GMP formation, this effect was partially reverted by sodium orthovanadate, a phosphotyrosine phosphatase inhibitor. Our results further demonstrate the presence of two ANG receptor subtypes in adrenal medulla: ANG binding to AT, receptor stimulates inositol phospholipid metabolism, whereas ANG binding to AT2 receptors decreases both inositol phosphate production and cGMP formation.

Adrenal Medulla↗
PubMed1995

Effect of yogurt on symptoms and kinetics of hydrogen production in lactose-malabsorbing children.

Lactase-deficient adults demonstrate improved lactose absorption and fewer symptoms when consuming yogurt than when consuming milk containing equivalent amounts of lactose. To examine this effect and its mechanisms in children, we compared symptoms and hydrogen production as an index of lactose malabsorption after typical servings of milk, pasteurized yogurt, and yogurt containing active live culture in 14 lactose-malabsorbing children (mean age 9.5 y). Symptoms and interval breath-hydrogen concentrations were recorded for 8 h after ingestion of 12 g lactose served as milk and yogurts. Lactose-malabsorbing children experienced significantly fewer symptoms after consuming yogurt containing active cultures than after consuming milk (P < 0.005). Pasteurized yogurt showed an intermediate effect. Lactose from yogurt was not better absorbed than was lactose from milk, as indicated by similar areas under the hydrogen curve; however, yogurt was associated with a delayed time to rise and lower rate of rise of the hydrogen curve. The rate of hydrogen rise correlated with the degree of symptoms. In children, mechanisms other than enhanced lactose absorption from yogurt may lead to changes in the kinetics of hydrogen production, which in turn are associated with improved tolerance.

Adolescent↗
PubMed1995

Effect of milks inoculated with Lactobacillus acidophilus or a yogurt starter culture in lactose-maldigesting children.

Dairy products containing live bacteria that possess lactase activity are used for dietary management of lactose maldigestion. The efficacy of acidophilus milk and the effect of consuming unfermented milk that had been inoculated with yogurt bacteria have not been examined in children. We compared scores for breath H2 excretion and symptoms of 20 lactose-maldigesting children following ingestion of 250 ml of uninoculated milk with two identical milks inoculated with 10(10) cells of Lactobacillus acidophilus or with a commercial yogurt starter culture containing 10(8) cells of Lactobacillus lactis and 10(10) cells of Streptococcus thermophilus. Nine of 10 subjects who were symptomatic following ingestion of uninoculated milk experienced a reduction in symptoms following ingestion of milk inoculated with L. acidophilus, without a decline in H2 excretion. Five of 6 subjects who were symptomatic following uninoculated milk had decreased symptoms and a significant reduction in H2 excretion following milk inoculated with the yogurt culture. For lactose-maldigesting children, milks inoculated with L. acidophilus or with a yogurt culture were associated with decreased symptoms compared with those with uninoculated milk.

Adolescent↗
PubMed1995

Selective peptide and nonpeptide ligands differentially bind to angiotensin II AT2 receptor and a non-angiotensin II CGP42112 binding site.

[125I]CGP42112 [Nic-Tyr-(epsilon-CBZ (benzyloxycarbonyl)-Arg)Lys-His-Pro-Ile] does not only recognize angiotensin II AT2 receptors, but has also the capacity to label a high-affinity, non-angiotensin II binding site, selectively associated with macrophages and activated microglia. We have searched for the structural requirements of the novel CGP42112 binding site, and compared these with the requirements for binding to the angiotensin II AT2 site. We designed a series of CGP42112 analogs and evaluated the new compounds by using binding assays on rat spleen (CGP42112 site) and rat fetal (angiotensin II AT2 site) membranes. The non-peptidic analog Z-Arg(Pmc)OH (N alpha CBZ-NG-2,2,5,7,8-pentamethylchroman-6-sulphonyl-L-Arg), the side chain of CGP42112 substituted on the guanidinium group, was selective in recognizing the CGP42112 site, and did not displace binding from the angiotensin II AT2 site. This is a potential lead compound for development of CGP42112 site-selective analogs. Conversely, the CGP42112 analog lacking the CBZ-group (Nic-Tyr-(Ac-Arg)Lys-His-ProOH, III) and the peptide Nic-Tyr-Lys-His-Ala-HisOH (VI), were selective for the angiotensin II AT2 site, and recognized the CGP42112 site poorly. Our results demonstrate that the structural requirements for the nonangiotensin II CGP42112 and the angiotensin II AT2 binding sites are different. We propose that the CBZ group and the free carboxyl terminal group, together with their spatial orientation, are key components of the molecule for the interaction in the non-angiotensin CGP42112 binding pocket.

Amino Acid Sequence↗
PubMed1995

Quantification and localisation of angiotensin II receptors and angiotensin converting enzyme in the developing rat heart.

OBJECTIVE: The aim was to determine the quantification and localisation of angiotensin II receptors and angiotensin converting enzyme (ACE) in the developing rat heart. METHODS: Quantitative autoradiography was used to determine the density of [125I]Sar1-angiotensin II binding to angiotensin II receptors and the density of [125I]351A binding to ACE. RESULTS: Angiotensin II receptors were first detected in the myocardium on embryonic day 14, and reached a maximum density within the first postnatal week. During the perinatal period, the density of angiotensin II receptors was twofold higher in atrial than in ventricular myocardium [27(SEM 7) v 11(1) fmol.mg-1 protein]. By adulthood, however, the density of angiotensin II receptors did not differ between atria and ventricles. A high density of angiotensin II receptors was first detected in the cardiac vasculature on embryonic day 19, with binding density decreasing during development. During the embryonic and early postnatal periods, most of the binding in the cardiac vasculature was to AT2 receptors. ACE was first detected in the myocardium on the day of birth, with the density of binding to ACE increasing during development. On postnatal day 56, the density of binding to ACE was fourfold higher in atrial than in ventricular myocardium [99(22) v 22(4) fmol.mg-1 protein]. A moderate density of binding to ACE was first detected in the cardiac vasculature and heart valves on embryonic day 19, with binding density increasing during development. By adulthood, the density of binding to ACE was 10- to 25-fold higher in the cardiac vasculature and heart valves than in the myocardium. CONCLUSIONS: The density of angiotensin II receptors and the density of binding to ACE are developmentally regulated in the heart. Both AT1 and AT2 receptors were present in the rat heart by late gestation and could, therefore, mediate the effects of angiotensin II on early cardiac growth and development.

Angiotensin II↗
PubMed1994

Angiotensin II AT1 receptor mediated contraction of the perfused rat cerebral artery.

The effect of angiotensin II on rat cerebral arteries was studied using isolated, perfused segments of anterior cerebral arteries. The infusion rate was set to maintain baseline intraluminal pressure at 75 mmHg. Angiotensin II (100 nM) increased the intraluminal pressure by 22.5 +/- 2.2 mmHg. Losartan, an AT1 antagonist, at 1 microM, completely blocked the effect of angiotensin II, whereas the AT2 ligands PD 123319 (1 microM) and CGP 42112 (1 microM) were ineffective. None of these AT1 or AT2 selective ligands alone displayed any agonist effects. The results show that angiotensin II induces contraction of the rat anterior cerebral artery by acting on AT1 receptors.

Angiotensin II↗
PubMed1994

Feeding of Bifidobacterium bifidum and Streptococcus thermophilus to infants in hospital for prevention of diarrhoea and shedding of rotavirus.

Acute diarrhoea is a serious cause of infant morbidity and mortality, and the development of preventive measures remains an important goal. Bifidobacteria (which constitute the predominant intestinal flora of breastfed infants), as well as other lactic-acid-producing organisms such as Streptococcus thermophilus, are thought to have a protective effect against acute diarrhoeal disease. However, their efficacy has not been assessed in controlled trials. In a double-blind, placebo-controlled trial, infants aged 5-24 months who were admitted to a chronic medical care hospital were randomised to receive a standard infant formula or the same formula supplemented with Bifidobacterium bifidum and S thermophilus. Patients were evaluated daily for occurrence of diarrhoea, and faecal samples, obtained weekly, were analysed for rotavirus antigen by enzyme immunoassay. Faecal samples were also obtained during an episode of diarrhoea for virological and bacteriological analyses. 55 subjects were evaluated for a total of 4447 patient-days during 17 months. 8 (31%) of the 26 patients who received the control formula and 2 (7%) of 29 who received the supplemented formula developed diarrhoea during the course of the study (p = 0.035, Fisher's exact test, two-tailed). 10 (39%) of the subjects who received the control formula and 3 (10%) of those who received the supplemented formula shed rotavirus at some time during the study (p = 0.025). The supplementation of infant formula with B bifidum and S thermophilus can reduce the incidence of acute diarrhoea and rotavirus shedding in infants admitted to hospital.

Acute Disease↗
PubMed1994

Expression of a novel non-angiotensin II [125I]CGP 42112 binding site in healing wounds of the rat brain.

We characterized a novel non-angiotensin II binding site that is recognized by the angiotensin II AT2 receptor ligand [125I]CGP 42112, in healing brain wounds of adult rats. The binding, which was highest at 3 days after injury, appears to be localized to activated microglia surrounding the wound. The novel CGP 42112 binding site may have a role in the function of microglia and in mechanisms of tissue repair in the brain.

Angiotensin II↗
PubMed1994

Angiotensin II AT2 receptor stimulation increases cerebrovascular resistance during hemorrhagic hypotension in rats.

The effects of the angiotensin II (ANG II) AT2 ligand PD 123319 and the AT1 antagonist losartan on cerebral blood flow (CBF) were studied during hemorrhagic hypotension in anesthetized rats using laser-Doppler flowmetry. In the control group CBF remained stable when mean arterial blood pressure (MABP) was lowered from 84 mmHg (baseline) to 45 mmHg, whereafter there was a pressure dependent decrease in CBF indicating inadequacy of autoregulation. Cerebrovascular resistance (CVR) was reduced until MABP 40 mmHg, where a maximum dilation was reached. PD 123319 dose-dependently (3-30 mg/kg i.v.) increased CVR through all blood pressures. Losartan 3 mg/kg i.v. had an effect similar to PD 123319. Selective stimulation of AT2 receptors with intravenous ANG II infusion, in the presence of AT1 receptor blockade by losartan, also increased CVR. As a result, reduced CBF was seen in the treatment groups. The effects of ANG II and PD 123319 30 mg/kg were antagonized by the nonselective ANG II antagonist Sar1,Ile8-ANG II (4 micrograms/kg/min i.v.). None of the treatments affected baseline CBF. The results confirm that ANG II contributes to cerebrovascular resistance and participates in the regulation of CBF apparently through AT2 receptors.

Analysis of Variance↗
PubMed1994

Specific, non-angiotensin, [125I]CGP 42112 binding sites in rat spleen macrophages.

We report the novel expression of a high affinity non-angiotensin II binding site to [125I]CGP 42112, predominantly localized to the red pulp of the rat spleen and to isolated rat spleen macrophages. Binding is not inhibited by angiotensin II, related peptides or AT1 or AT2 receptor ligands, and is not affected by several growth factors and cytokines involved in macrophage function. Thus, CGP 42112 recognizes binding sites other than angiotensin II AT2 sites in rat macrophages. CGP 42112 and related peptides might influence the regulation of macrophage function.

Amino Acid Sequence↗
PubMed1994

[125I]CGP 42112 reveals a non-angiotensin II binding site in 1-methyl-4-phenylpyridine (MPP+)-induced brain injury.

1. Intracerebral injection of the oxidative metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 1-methyl-4-phenylpyridine (MPP+), into the substantia nigra of adult rats resulted in a lesion at the injection site. 2. Using autoradiography, we localized specific [125I]CGP 42112 binding that was not recognized by angiotensin II or angiotensin II AT1 or AT2 receptor-selective ligands. 3. Our results suggest that [125I]CGP 42112 may be binding to activated microglia that appear at the lesion site.

1-Methyl-4-phenylpyridinium↗
PubMed1994

Successful intestinal transplantation for microvillus inclusion disease.

Microvillus inclusion disease is a rare congenital disorder that presents with severe diarrhea in the newborn period. Multiple therapeutic attempts to control the diarrhea have failed, leading to a chronic dependence on parenteral nutrition and a high infant mortality. This report presents the first child with microvillus inclusion disease in whom small bowel transplantation has been successful, allowing for the administration of total caloric requirements via the enteral route.

Cytomegalovirus Infections↗
PubMed1994

Autoradiographic localization and characterization of angiotensin II receptor subtypes in the rat thymus.

Angiotensin II (ANG II) receptors were present in the thymus of newborn rats (179 +/- 34 fmol/mg protein). In newborns, binding was predominantly localized in the trabecula, and was selectively displaced by the AT2 ligand CGP 42112A (83-85%) and to a lower extent by the AT1 antagonist losartan (15-17%), indicating a marked predominance of AT2 receptors. Angiotensin II binding was very low in the cortical and medullary areas in the thymus of newborn rats and was no longer detected in the thymus of 4- and 8-week-old rats. No detectable binding for the ACE inhibitor [125I]351A was observed in the thymus of the rat, regardless of the age studied. Our results indicate a possible role for circulating ANG II during development of the thymus with no clear correlation to lymphocyte maturation.

Animals↗