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Biomedical subjects

H Ong

Publications and source records attributed to H Ong.

101 records · Page 6Linked to original sources
PubMedDate not supplied

Effect of atrial natriuretic factor on plasma vasopressin in conscious rats.

An intravenous (IV) bolus injection (10 micrograms) of synthetic rat atrial natriuretic factor [ANF (Arg 101-Tyr 126)] into normal conscious Sprague-Dawley rats produced a significant decrease of plasma arginine vasopressin (AVP) while 1-, 2- and 5-micrograms doses exerted no such effect. Mean arterial blood pressure (MAP) was lowered about 15 mmHg by an IV 10 micrograms bolus injection of ANF. When plasma AVP rose significantly in rats exposed to such osmotic stimuli as 600 mM NaCl and 900 mM mannitol intraperitoneally (IP), subsequent IV injection of ANF (10 micrograms) markedly depressed this parameter. Lower doses of ANF were ineffective against 600 mM NaCl IP. The significant elevation of plasma AVP levels by hypertonic sucrose 900 mM IP was not modified by ANF (10 micrograms). Blood pressure remained unchanged after IP administration of various osmotic stimuli, except mannitol, and in all these experiments an IV bolus of ANF exerted a lowering effect on MAP. Seventy-two hr water deprivation (mixed osmotic and volume stimulus) resulted in elevated plasma AVP levels which were unaffected by an IV bolus injection of ANF at doses of 0.06-10 micrograms. Immunoreactive ANF (IR-ANF) rose in plasma to 39.3 +/- 13 ng/ml 1 min after an IV bolus injection of 10 micrograms ANF, dropping to 1.01 +/- 0.2 ng/ml after 5 min and to 0.32 +/- 0.01 ng/ml after 10 min (when ANF and AVP interactions were studied), but still remained approximately six times higher than in control rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Localization and identification of immunoreactive atrial natriuretic factor (ANF) in the frog ventricle.

The localization of ANF-like immunoreactivity in the ventricle of the frog Rana ridibunda was examined by the indirect immunofluorescence and the immunogold techniques, using an antiserum against synthetic ANF (Arg 101-Tyr 126). At the optic level, an appreciable number of positive cardiocytes was observed in the frog ventricle. Electron microscopic studies showed that all secretory granules present in ventricular cardiocytes contain immunoreactive ANF. The immunoreactive material has been characterized by Sephadex G-50 gel chromatography and reverse phase high performance liquid chromatography (RP-HPLC). After gel filtration, ANF-like immunoreactivity eluted in 3 peaks. The major immunoreactive peak corresponded to high molecular weight material, while one peak co-eluted with synthetic ANF (Arg 101-Tyr 126). Further analysis of frog ventricular extracts by RP-HPLC revealed that the low molecular weight material has the same retention time as synthetic ANF, suggesting a high degree of sequence homology between amphibian and mammalian ANF. These results indicate that in amphibians, ventricular cardiocytes synthesize a peptide immunologically and chemically related to mammalian ANF.

Animals↗
PubMedDate not supplied

Differential regulation of natriuretic peptide biosynthesis in bovine adrenal chromaffin cells.

Chromaffin cells synthesize and secrete two forms of natriuretic peptides which are also found in the heart and in the central nervous system. While atrial tissue predominantly contains atrial natriuretic factor (ANF), brain tissue appears to produce relatively larger amounts of brain natriuretic peptide (BNP) also identified as aldosterone secretion inhibitory factor (ASIF), suggesting tissue-specific differential regulation of these two peptides. This report compares the modulation of the biosynthesis and secretion of ASIF with that of ANF using cultured chromaffin cells as a model system. Cholinergic nicotinic activation and KCl depolarization induce a 5-fold increase of the corelease of ASIF and pro-ASIF in cell culture medium concomitantly with a 3-fold stimulation of ANF and pro-ANF cosecretion. While the combined treatment with phorbol ester and forskolin produces a 2-fold increase in total ANF level, it induces a synergistic 20-fold elevation of total ASIF level. These results indicate that chromaffin cell secretagogues induce the cosecretion of both the precursor and mature forms of ASIF and ANF. The preferential stimulation of ASIF production is revealed by the combined treatment rendering the ASIF to ANF proportion similar to that in brain.

Adrenal Medulla↗
PubMedDate not supplied

Endogenous atrial natriuretic factor after endopeptidase 24.11 inhibition by Thiorphan.

The neutral endopeptidase 24.11 (NEP) was shown to degrade atrial natriuretic factor (ANF) in kidney membranes. An infusion of Thiorphan (25 micrograms/min/kg x 90 min), a specific NEP inhibitor, induced an increase in plasma ANF (65 +/- 26 to 163 +/- 52 pg/ml), plasma renin activity and in norepinephrine concentrations at 50 minutes of infusion in conscious rabbits. The increase in plasma ANF was accompanied by a gradual decrease in renal blood flow, despite maintenance of a stable mean arterial pressure. In conclusion, Thiorphan infusion produced an increase in endogenous plasma ANF. However, it may also have affected other hormonal systems which may have contributed to the overall dynamic and hormonal profile documented.

Aldosterone↗
PubMedDate not supplied

Role of the endopeptidase 24.11 in the disposition and metabolism of endogenous atrial natriuretic factor in the rabbit.

The neutral endopeptidase 24.11 (NEP) has been shown to inactivate the atrial natriuretic factor (ANF) by opening the ring structure. To document the role of NEP in the metabolic fate of ANF in vivo, the effects of an infusion of thiorphan (25 micrograms/min/kg), a specific NEP inhibitor, on the kinetics and metabolism of endogenous ANF were studied in conscious rabbits. A bolus of [125I]ANF(99-126) was injected 50 min after the beginning of the infusion of thiorphan. Plasma samples containing the radioactive peptides were separated by reverse-phase HPLC. The parent compound could be separated from at least two other minor metabolites, corresponding to the elution position of [125I]ANF(99-105/106-126), the inactive ring-opened metabolite, and of [125I]ANF(103-126), an N-truncated analog. The generation of the N-truncated metabolite was increased by thiorphan. Thiorphan also induced an increase in plasma ANF (29%) that was closely associated with a 32% reduction in the systemic clearance of [125I]ANF(99-126), whereas no modification in the estimated secretion rate was detected. These results support a role for NEP in the regulation of endogenous ANF plasma levels. These results also suggest that specific inhibition of NEP may result in an increase in the apparent activity of alternative metabolic pathways.

Animals↗
PubMedDate not supplied

Determination of diclofenac sodium and related compounds in raw materials and formulations.

A liquid chromatographic method has been developed for determination of drug and related compounds in diclofenac sodium raw material, slow-release, and enteric coated tablets. The method specifies a 5 microns octadecylsilane bonded phase column, a mobile phase of tetrahydrofuran-acetonitrile-buffer, pH 5 (1 + 4 + 8.3), and detection at 229 nm. The method resolves 10 known related compounds with limits of quantitation of 0.2% or less. Seventeen drug raw material samples were evaluated. Total impurity levels ranged from 0.1 to 0.9%. The method has also been used for determination of drug content in raw materials and formulations. Mean assay levels in drug raw materials ranged between 98.3% and 101.8%.

Chromatography, Liquid↗
PubMedDate not supplied

In vivo study of propranolol and metabolite(s) disposition in rat liver.

To investigate the intrahepatic disposition of drugs subjected to the first-pass effect, propranolol (0.002 mg/kg and 5 mg/kg) was injected into the portal vein of rats. At various times the drug was measured in liver homogenate, cytosol, smooth microsomal, and Golgi fractions. The results suggest that hepatic uptake of propranolol is an extremely rapid process and essentially complete, independently of the dose. Effectively at 0.5 min, 70% and 85% of the low and high doses, respectively, were recovered in the liver homogenate. Furthermore following the 0.002-mg/kg dose, 96% of the recovered drug equivalents in the suprahepatic blood consisted of metabolites. An additional experiment demonstrated that the uptake of a 0.002-mg/kg dose of propranolol was not modified by a loading dose of 25 mg/kg. The pattern of propranolol distribution correlated with the intracellular localization of phospholipids and proteins. The amount of propranolol found in subcellular fractions relative to liver homogenate remained constant throughout the study, suggesting a rapid equilibrium. Low doses of propranolol were cleared from the hepatic cells almost completely by biotransformation. However, high doses saturated the metabolic clearance. Propranolol metabolites accumulated preferentially in the cytosol fraction. The intracellular elimination of the metabolites appeared to be a saturable process. The Golgi apparatus does not seem to be involved in the elimination of propranolol or its polar metabolites.

Animals↗
PubMedDate not supplied

Hepatic and extrahepatic metabolism of salbutamol in anesthetized rabbits.

Orally administered salbutamol undergoes an extensive first-pass effect. This study investigated the roles of the intestine (INT), liver (HEP), and lung (LUN) in salbutamol extraction. Salbutamol was administered to five groups of anesthetized rabbits by the following routes: intraduodenal (ID) (800 micrograms/kg), intraportal (IP), (60 micrograms/kg), intrajugular (IV) (60 micrograms/kg), endotracheal (ET) (60 micrograms/kg), and intraarterial (IA) (60 micrograms/kg). Multiple blood samples were drawn and the areas under salbutamol plasma concentrations-time curves (AUCs) were calculated. Since IA salbutamol administration generated 100% bioavailability (F), AUCIA was used as a reference for comparison. Salbutamol F values for the ID, IP, IV, and ET routes were 0.013, 0.15, 0.53, and 0.53, respectively. The ratio of the AUC of salbutamol administered before the organ (ID, IP, IV, or ET) to the AUC estimated when given after the organ (IP, IV, and IA) allowed assessment of the extraction ratio (E) of INT, HEP, and LUN, respectively. EINT was 0.92, EHEP was 0.71, and ELUN was 0.47. The mean ratio of the AUC of the metabolite (AUCM) over the AUC of the parent compound was 704 +/- 77 for the ID, compared with 83 +/- 12 for the IP, 11 +/- 1 for the IV, 1.7 +/- 0.3 for the ET routes, and 4 +/- 1 for the IA routes. On the other hand, when the AUCM was normalized by the dose, this ratio was INT = HEP > LUN, suggesting that the ability of INT to conjugate salbutamol is not very important.(ABSTRACT TRUNCATED AT 250 WORDS)

Albuterol↗