James McQueen

Fetal angiotensin II levels and vascular (type I) angiotensin receptors in pregnancies complicated by intrauterine growth retardation

Objective To investigate the status of the fetal renin‐angiotensin system (RAS) in pregnancies complicated by severe intrauterine growth retardation (IUGR), and its possible relationship to elevated fetoplacental vascular resistance as indicated by abnormal umbilical artery Doppler flow velocity waveforms (FVW).

The influence of the lexicon on phonetic categorization: stimulus quality in word-final ambiguity

The categorization of word-final phonemes provides a test to distinguish between an interactive and an autonomous model of speech recognition. Word-final lexical effects ought to be stronger than word-initial lexical effects, and the models make different reaction time (RT) predictions only for word-final decisions. A first experiment found no lexical shifts between the categorization functions of word-final fricatives in pairs such as fish-fiss and kish-kiss. In a second experiment, with stimuli degraded by low-pass filtering, reliable lexical shifts did emerge. Both models need revision to account for this stimulus-quality effect. Stimulus quality rather than stimulus ambiguity per se determines the extent of lexical involvement in phonetic categorization. Furthermore, the lexical shifts were limited to fast RT ranges, contrary to the interactive models predictions. These data therefore favor an autonomous bottom-up model of speech recognition.

Angiotensin II increases proto-oncogene expression and phosphoinositide turnover in vascular smooth muscle cells via the angiotensin II AT1 receptor

Objectives: The aim of this study was to determine which angiotensin II receptor (AT receptor) mediates proto‐oncogene expression and phosphoinositide metabolism in vascular smooth muscle cells in vitro. Design: The AT receptor antagonists DuP753 (losartan), an AT1 antagonist, and PD 123319, an AT2 antagonist, were used to characterize AT receptors on cultured vascular smooth muscle cells derived from the rat mesenteric artery and to identify which receptor subtype mediates the angiotensin II‐induced increase in proto‐oncogene expression and phosphoinositide metabolism. Methods: Rat mesenteric artery vascular smooth muscle cells were grown using standard cell culture methods. Proto‐oncogene induction was measured using Northern blotting. Phosphoinositide breakdown was assessed by measuring [3H]‐inositol phosphates released from prelabelled cells. Results: Receptor‐binding studies revealed that the AT1 receptor predominated on vascular smooth muscle cells. Incubation of quiescent cells with 0.1 μmol/l angiotensin II resulted in a 65% increase in total [3H]‐inositol phosphates released compared with unstimulated cells and in a rapid accumulation of c‐fos messenger RNA (mRNA). Pre‐incubation of the cells with 10−5mol/l PD 123319 had no effect on either total inositol phosphates release or c‐fos mRNA induction. Both responses, however, were totally abolished by pre‐incubation of the cells with 10−5mol/l losartan or saralasin. Conclusions: Angiotensin II acts through the AT1 receptor to increase c‐fos expression and phosphoinositide turnover in vascular smooth muscle cells. These mechanisms may be important in angiotensin II‐induced smooth muscle hypertrophy.

Maternal and fetal atrial natriuretic peptide levels at delivery from normal and growth retarded pregnancies

Objective To determine whether circulating fetal levels of the vasodilator atrial natriuretic peptide (ANP) are reduced in pregnancies complicated by intrauterine growth retardation (IUGR).

Angiotensin Receptor Assay and Characterization

Publisher Summary This chapter reviews the methods used for characterization and quantification of the angiotensin receptor in different cells and tissues. Angiotensin II (AII) has effects on many tissues, mostly related to cardiovascular regulation and electrolyte homeostasis. Angiotensin peptides are readily radioiodinated at the tyrosine position using chloramine-T, lactoperoxidase, and solid-phase Iodogen methods. The latter method causes minimal oxidation damage to the peptide and is preferred. The chapter discusses the effects of ligand degradation and the use of peptidase inhibitors in receptor assays. The nonpeptide compounds act as pure competitive antagonists. High-affinity binding to a Golgi fraction from liver has been shown to represent receptors internalized from the cell surface. Receptor internalization has also been observed in cultured cells and in adrenal cortex in vivo, and intracellular receptors may be present in these and other tissues. In general, membrane fractions are used for receptor identification and characterization, and for quantification in altered physiological or pathological states. Internalized receptors appear to be rapidly recycled to the cell surface after release and subsequent degradation of the ligand, measuring the total cell receptor number, may, therefore, provide a valid measure of cell or tissue responsiveness to AII.

Preliminary observations on the role of atrial natriuretic peptide in the fetoplacental circulation

Summary These preliminary observations suggest a possible role for ANP in the regulation of fetoplacental blood flow. Specific binding sites have been identified using a newly-described technique of dissecting out the vascular core of the primary and secondary stem villi. A five-fold reduction in maximal binding of ANP in pregnancies complicated by intrauterine growth retardation as compared to normal controls suggests one possible mechanism whereby increased fetoplacental vascular resistance occurs in this condition.