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Biomedical subjects

R Garcia

Publications and source records attributed to R Garcia.

At least 307 records · Page 17Linked to original sources
PubMed1989

Diltiazem enhances gentamicin nephrotoxicity in rats.

The effect of the calcium antagonist, diltiazem, was examined in gentamicin-induced nephrotoxicity states in rats. Animals were injected for 5 days with diltiazem intraperitoneally (40 mg/kg/day), or gentamicin subcutaneously (100 mg/kg/day) or simultaneously with both preparations using the same doses. At the time of sacrifice, the urea and creatinine clearances, as well as urine osmolality were determined and the renal tissues were processed for examination by light microscopy. Gentamicin-injected rats demonstrated the typical pattern of aminoglycoside nephrotoxicity characterized by poliuric renal failure and necrosis of the proximal tubular epithelium. Rats injected with diltiazem revealed only mild depression of urine osmolality. There was no elevation of blood urea nitrogen and serum creatinine or depression of urea and creatinine clearances, and no focal tubular cell necrosis was detected. However, concomitant administration of both compounds considerably increased nephrotoxicity by according both histological indications and renal function measurements. Thus, we conclude that the combination of diltiazem and gentamicin must be used carefully in human clinical practice.

Acute Kidney Injury↗
PubMed1989

Glomerular and vascular atrial natriuretic factor receptors in adrenalectomized rats.

The renal and vascular responses to atrial natriuretic factor (ANF) and glomerular and vascular ANF receptors were studied in adrenalectomized (ADR) rats with or without deoxycorticosterone (DOC) or dexamethasone (Dexa) replacement therapy. As expected, adrenalectomy elicited hypotension, hemoconcentration, and increased plasma renin activity, but no changes in plasma levels of either ANF-(1-98) or ANF-(99-126) were detected. Dexa treatment decreased both ANF-(1-98) and ANF-(99-126), whereas DOC treatment increased only ANF-(1-98). The acute renal response to ANF and furosemide was reduced in ADR rats and partially restored either by steroid replacement or by raising blood pressure. The blunted natriuretic response to ANF in ADR rats was associated with an increased density of glomerular receptors. Norepinephrine-precontracted vascular strips from ADR rats were more sensitive to ANF (ED50: 1.7 x 10(-8) M) than those from sham-operated animals (ED50: 1.5 x 10(-7) M). However, vascular ANF receptor density in mesenteric vessels from ADR animals was decreased. Dexa treatment restored vascular response to that observed in sham-operated animals without a concomitant change in vascular receptor density. Because the presence of guanylate cyclase-coupled and noncoupled ANF receptor subtypes have been described in different tissues, we conclude that the apparent lack of correlation between the biological response to ANF and total binding of ANF to glomeruli or mesenteric artery membranes in ADR rats may be in part caused by a differential regulation of both receptor subtype populations.

Adrenalectomy↗
PubMed1989

Glomerular atrial natriuretic factor receptors in spontaneously hypertensive rats.

There are differences in the renal handling of sodium between spontaneously hypertensive rats (SHR) and their normotensive controls. We investigated whether this difference may be associated with changes in plasma and tissue atrial natriuretic factor (ANF) levels and with alterations in glomerular ANF receptors at 4, 8, 12, and 16 weeks of age. Age-matched Wistar-Kyoto (WKY) and Wistar rats were used as normotensive controls. Systolic blood pressure was higher in SHR at 8, 12, and 16 weeks, and cardiac hypertrophy was also present in these animals at 4 weeks. Plasma ANF C- and N-terminal concentrations were greater than in both normotensive groups at 8 and 16 weeks. ANF in the right atrium was higher in SHR than in WKY rats and identical to that in the Wistar group at 4 and 8 weeks. ANF in the left atrium was lower in SHR than in both control groups at week 12. No differences were found in ventricular ANF content. The density of glomerular ANF binding sites increased with age in WKY and Wistar rats but not in SHR. At weeks 8, 12, and 16, both normotensive groups had a higher density of binding sites than SHR, but binding site affinity was greater in SHR at weeks 8 and 12. After incubation with increasing concentrations of ANF, the production of cyclic guanosine monophosphate (cGMP) by isolated glomeruli from 16-week-old rats was lower in SHR than in both normotensive groups. We conclude that the development of hypertension in SHR is associated with higher plasma ANF levels and decreased glomerular ANF receptor density and glomerular cGMP production.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Atrial natriuretic factor in Purkinje fibers of rabbit heart.

The Purkinje fibers of the rabbit false tendons (chordae tendineae spuriae) are endocrine cells containing immunoreactive atrial natriuretic factor (ANF) and ANF messenger RNA (mRNA). These cells, as visualized by immunocryoultramicrotomy, contain immunoreactive ANF in their secretory granules and their Golgi complex and exhibit ANF mRNA, as visualized by in situ hybridization with an ANF complementary RNA probe. The content of immunoreactive ANF and ANF mRNA of the Purkinje fibers is midway between that of atrial and ventricular working cardiocytes. High-pressure liquid chromatography analysis of immunoreactive ANF using antibodies against the C-terminal and N-terminal moieties of the molecule indicates that part of immunoreactive ANF contained in Purkinje fibers is the propeptide [Asn1,Tyr126]ANF whereas part was nonspecifically cleaved into C-terminal and N-terminal ANF. The chordae tendineae spuriae exhibit binding sites for ANF (Kd:approximately 1.0 nM; Bmax:approximately 2.3 fmol/mg). ANF profoundly decreases basal and stimulated (epinephrine, dopamine, isoproterenol, and forskolin) adenylate cyclase activity and cyclic adenosine monophosphate (AMP) levels. ANF has little effect on norepinephrine-stimulated adenylate cyclase activity or on norepinephrine-stimulated cyclic AMP levels. ANF produces only a slight increase in guanylate cyclase activity and cyclic guanosine monophosphate levels at high (10(7)-10(6) M) concentrations. These results suggest an autocrine function for ANF in the modulation of the impulse in the peripheral conduction cells (Purkinje fibers) of the rabbit through changes in second messenger levels.

Animals↗
PubMed1989

Ventricles as a major site of atrial natriuretic factor synthesis and release in cardiomyopathic hamsters with heart failure.

The aim of the present study was to correlate in cardiomyopathic hamsters with congestive heart failure the levels of atrial and ventricular atrial natriuretic factor (ANF) messenger RNA (mRNA) with immunoreactive ANF (IR-ANF) plasma levels and the relative amount of IR-ANF released by the whole heart versus isolated ventricles in the Langendorff preparation. High-performance liquid chromatography analysis of the forms of ANF present in plasma and in the Langendorff effluent of whole heart versus isolated ventricles was also performed. As previously found for cardiac IR-ANF, the levels of ANF mRNA decreased gradually in atria and increased in an analogous fashion in ventricles with the severity of congestive heart failure. Plasma IR-ANF levels (C-terminal) were more elevated in moderate than in severe congestive heart failure, as were the IR-ANF levels in the Langendorff effluent of the whole heart. On the contrary, the effluent of isolated ventricles from animals in severe heart failure yielded more IR-ANF than that from hamsters in moderate heart failure. Thus, while the isolated ventricles from controls contributed 35.8% of IR-ANF released by the whole heart, ventricles from hamsters in moderate heart failure contributed 17.5%, and those from hamsters in severe heart failure contributed 73.9%. These results indicate that atrial cardiocytes contribute more IR-ANF than their ventricular counterpart in moderate heart failure and that ventricles are a major source of plasma IR-ANF in severe heart failure. Analysis of IR-ANF from plasma and the Langendorff effluent from whole hearts and isolated ventricles revealed that the ventricles are the major source of the propeptide (and of its cleaved products) found in the circulation of cardiomyopathic hamsters. These results suggest that ANF synthesis and secretion do not increase conjointly in atria but do increase in ventricles during congestive heart failure.

Animals↗
PubMed1989

Dissociation of natriuresis and diuresis and heterogeneity of the effector system of atrial natriuretic factor in rats.

The hypotensive, natriuretic, and diuretic actions of human atrial natriuretic factor-(99-126) (hANF) are accompanied by an elevation of cyclic guanosine monophosphate (cGMP) in plasma and urine. However, the oxidized hANF analogue, human [Met-O110]ANF-(99-126) (Met-O-ANF), has been reported to be unable to increase cGMP (Biochem. Biophys. Res. Commun. 128: 538-546). We employed this oxidized peptide to evaluate the relationship between its biological effects and cGMP generation, with cGMP serving as a marker of the recognized property of ANF to stimulate particulate guanylate cyclase. Met-O-ANF appeared to be a partial agonist, exhibiting a decreasing order of relative potency of hypotensive, vasorelaxant, diuretic, and natriuretic functions compared to hANF. A lower degree of cGMP increases was achieved by this analogue in cultured smooth muscle and endothelial cells. Met-O-ANF doses, which led to a significant increase in diuresis, were neither natriuretic nor accompanied by an increase of urinary cGMP. We were thus able to dissociate the diuretic and natriuretic effects of ANF. High doses of the oxidized analogue were required to elevate cGMP levels in plasma and urine. In isolated kidney fractions, Met-O-ANF's action on cGMP was significantly lower in glomeruli (fivefold less), virtually absent in the collecting duct, yet only slightly different (20% less) in thick ascending limb. Our results indicate that the diuretic and natriuretic effects are exerted at distinct sites, with only the natriuresis being related to an increase of extracellular cGMP. The variability of differential potency of biological and biochemical effects from tissue to tissue of these two forms of human ANF support the notion of the heterogeneity of the ANF effector system.

Animals↗
PubMed1989

Inhibition of pancreatic exocrine secretion in the rat by calcitonin gene-related peptide: involvement of circulating somatostatin.

Calcitonin gene-related peptide (CGRP), a 37-amino acid peptide, has been shown to be a potent inhibitor of pancreatic exocrine secretion when administered exogenously The present study was performed to determine if this inhibitory effect is due to the direct actions of exogenous CGRP on the exocrine pancreas or to the effects of another inhibitor released by CGRP. To this end, we first confirmed the inhibitory effects of the peptide on exocrine function by infusing the peptide into conscious rats previously prepared with bile-pancreatic fistulas and measuring cholecystokinin-stimulated amylase and protein outputs. CGRP produced a dose-dependent inhibition of both protein and amylase outputs in vivo. In marked contrast, CGRP in vitro had no direct inhibitory effect on amylase output from either the isolated buffer-perfused pancreas or dispersed acinar cells. Thus, the inhibitory effects of exogenous CGRP on pancreatic exocrine function appear to be indirect. In an attempt to determine the mediator of the inhibitory effects of CGRP, we assessed the ability of similar doses of CGRP to stimulate the release of a potential endogenous inhibitor of pancreatic exocrine function, circulating somatostatin. In conscious rats, iv CGRP dose-dependently increased circulating plasma somatostatin-like immunoreactivity from 35 +/- 5 to 86 +/- 7 fmol/ml. To determine if these increments in circulating somatostatin were sufficient to impair exocrine function, the isolated pancreas was exposed in vitro to a similar concentration of somatostatin. Somatostatin perfusion resulted in a significant inhibition of pancreatic amylase output (73%). Overall, these results support the hypothesis that 1) the inhibitory effect of exogenous CGRP on pancreatic exocrine function is indirect; 2) exogenous CGRP stimulates the release of endogenous somatostatin into the systemic circulation; and 3) the concentration of circulating somatostatin is sufficient to mediate the effect of exogenous CGRP on the exocrine pancreas.

Amylases↗
PubMed1989

Processing of the atrial natriuretic factor propeptide by atrial cardiocytes as revealed by immunocryoultramicrotomy.

Antibodies were raised against three fragments of the rat ANF molecule: C-terminal atrial natriuretic factor (ANF)-(101-126), N-terminal ANF-(11-37), and the putative cleavage site of the ANF propeptide, ANF-(94-103). These antibodies were purified by affinity chromatography and revealed a major band (17K) corresponding to the propeptide by Western blot analysis. Antibodies against ANF-(94-103) were used in a RIA. All of the peptides that possess this region (98-99) were able to displace iodinated pro-ANF from the antibody. However, peptides that have only one part of the fragment, such as ANF-(99-126) or ANF-(1-98), failed to displace pro-ANF; human ANF-(79-98) (100 pmol) demonstrated about 0.01% cross-reactivity. Immunohistochemical studies revealed that all atrial cardiocytes are reactive with the three antibodies. Immunocryoultramicrotomy revealed that the propeptide travels, uncleaved, from the Golgi complex to immature granules and mature secretory granules. These results indicate that cleavage of the ANF propeptide does not occur at these sites.

Animals↗
PubMed1989

Relaxing effect of atrial natriuretic factor on endothelin-precontracted vascular strips.

Endothelin (ET), a peptide recently isolated from the supernatant of cultured porcine aortic endothelial cells, is a potent vasoconstrictor. On the other hand, atrial natriuretic factor (ANF) is a powerful vasorelaxant found in cardiocytes. Its effect was investigated in ET-precontracted rabbit vascular strips. ANF-induced a dose-dependent relaxation of maximally-precontracted mesenteric, renal and aortic strips. Mesenteric artery strips were more sensitive to ANF than either renal or aortic strips. The relaxant effect of ANF on ET-precontracted arteries was more potent than that of other vasorelaxant agents, such as isoproterenol and sodium nitroprusside. Renal and aortic arteries were more sensitive to the vasoconstrictor effect of ET than mesenteric strips. From these results, we conclude that ANF may play a role as a physiological antagonist of ET. The different sensitivity of vascular segments to ET could be due to varying vascular ET receptor densities.

Animals↗
PubMed1989

[Indication of maxillary reduction in surgical-orthodontic protocols].

The LEFORT I maxillary impaction correction of the dento-alveolar vertical compensation improve the labial contact and allow to establish a better occlusion. The site, the symmetry and the importance of this impaction depend of the initial exo and endobuccal diagnosis. Three cases are studied to appreciate its clinical possibilities.

Cephalometry↗
PubMed1989

Atrial natriuretic factor release during angiotensin II infusion in right and left atrial appendectomized rats.

The effect of selective right or left atrial appendectomy on atrial natriuretic factor (ANF) release was studied in the rat to compare the relative contribution of each atrium in a situation of increased afterload. Sham-operated or right (RAA) or left (LAA) atrial appendectomized conscious rats were infused (intravenously) for 60 min with a pressor dose of angiotensin II (Ang II; 600 ng/kg per min). All groups presented a significant and similar elevation of mean arterial pressure (MAP) and left ventricular end-diastolic pressure (LVEDP). No change in central venous pressure (CVP) was noted in the LAA group, whereas a small, transient rise was observed in the two other groups. The Ang II-induced release of ANF C-terminal was blunted in the RAA group (P less than 0.01 versus sham) and more so in the LAA group (P less than 0.001 versus sham). Atrial natriuretic factor N-terminal release was blunted only in the LAA group (P less than 0.05 versus sham). No correlation was found between CVP and ANF in any group. The relationship between LVEDP and ANF in the sham-operated controls became weaker in the LAA group and was lost in the RAA group. We conclude that both atria play a role in the ANF release induced by a vasoconstrictor agent, but changes in left heart haemodynamics may be the first to be involved in the response to an increased afterload.

Angiotensin II↗
PubMed1989

Intramuscular and subcutaneous administration of atrial natriuretic factor in the rat.

The effects of ANF (99-126) and its active analog, [3-mercaptopropionic 105]-ANF (105-126), on diuresis and natriuresis were assessed in the rat after intramuscular (i.m.) or subcutaneous (s.c.) injection. Water and sodium excretion increased significantly after i.m. or s.c. administration of either peptide in the first 20-min urine collection. ANF (99-126) was more active i.m. than its analog, while they both produced similar diuresis and natriuresis when they were administered s.c. The rapid and significant increase of plasma IR-ANF levels, detected by radioimmunoassay and analyzed by high performance liquid chromatography after i.m. or s.c. injection of these peptides, indicates very rapid passage into the blood circulation without degradation. These data demonstrate that either the i.m. or s.c. route can be used to administer ANF or its analog.

Animals↗
PubMed1989

Effect of a chronic infusion of atrial natriuretic factor on glomerular and vascular receptors in spontaneously hypertensive rats.

To investigate the effect of a prolonged infusion of atrial natriuretic factor (ANF) on its vascular and glomerular receptors, ANF (Ser 99-Tyr 126) was chronically administered (100 ng/h) for 7 days by osmotic minipumps to spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Blood pressure in the SHR fell from 149 +/- 5 to 119 +/- 3 mmHg 5 days after the ANF infusion was initiated, whereas no changes were observed in ANF-infused WKY rats. The SHR had higher plasma levels of both ANF (1-98) and (99-126) than the normotensive controls, but the ANF infusion did not modify these values in either group. Diuresis, natriuresis and haematocrit remained unchanged during the infusion. The higher plasma ANF levels noted in the SHR were associated with a decreased density (Bmax) and enhanced affinity (Kd) of ANF-binding sites in the mesenteric vessels. This pattern was not modified by the ANF infusion. The hypertensive animals had glomerular ANF receptors with a higher affinity than the WKY rats. The Bmax of these receptors was decreased significantly in ANF-infused SHR and WKY rats compared with non-infused animals. We conclude that the lack of change in vascular ANF receptors, during chronic ANF infusion in the SHR, could be associated with the hypotensive response.

Animals↗
PubMed1988

Specific binding of atrial natriuretic factor to renal glomeruli during day or night antiorthostatic suspension in the rat.

We observed a significant increase in plasma atrial natriuretic factor (ANF) in antiorthostatic hypokinetic suspension (AOH) rats after 2 h of suspension when the experiment was made during day. Plasma ANF was investigated in relation to renal glomerular ANF receptors during AOH at night. The aim of this study was 1) to compare the day and night ANF responses to AOH 2) to determine whether the renal glomerular ANF receptors are involved. The rats were divided into 2 groups: i) 24 population cage (PC), and ii) 24 were attached by the tail (Morey's model) and remained in the horizontal position (attached horizontal-AH). Six AH were suspended (30 degrees) for 2 hours (AOH) and sacrificed with the controls: PC and AH (12.00h). The same experiment was made during the night (24.00h). A significant increase in plasma ANF was found in both AOH and AH after 2 h of suspension during day and night (19 +/- 2.3 pg/ml vs 9 +/- 0.95 and 18 +/- 3 pg/ml vs 10.2 +/- 1.8 respectively). PC rats had a significantly higher ANF level (38 +/- 5 pg/ml) than AH or AOH. The glomerular ANF receptor population was slightly lower in AOH than in AH (429 +/- 12 fmol/mg protein vs 507 +/- 5) during day. During night, a significantly lower number of ANF receptors was observed in AOH animals as compared to AH (168 +/- 2 fmol/mg protein vs 455 +/- 3). A decrease in glomerular receptors was also noted in PC during night. Day-time head-down tilt, bed rest or head-out water induced a natriuretic and diuretic response, whereas the normal recumbency at night does not lead to such effects. We conclude that the natriuretic and diuretic response not observed during night was associated with elevated plasma ANF levels and decreased ANF receptor density.

Animals↗
PubMed1988

Atrial natriuretic factor in experimental and human hypertension.

Plasma levels of immunoreactive atrial natriuretic factor (IR-ANF) were evaluated by radioimmunoassay in several models of experimental hypertension and in human hypertension. Plasma levels of IR-ANF are consistently increased in all models of experimental hypertension studied so far. This is accompanied by a decrease of IR-ANF levels in the left atrium at certain times. Plasma levels of IR-ANF are not increased in human essential hypertension, except in the severe form (diastolic blood pressure above 110 mmHg). Peripheral levels of IR-ANF in renovascular hypertension do not differ from normal but are increased above normal in aortic blood.

Animals↗