High NaCl diet enhances arterial baroreceptor reflex in NaCl-sensitive spontaneously hypertensive rats

Previous studies from our laboratory have shown that arterial baroreceptor reflex control of lumbar sympathetic nerve activity is blunted in the NaCl-sensitive spontaneously hypertensive rat (SHR-S) compared with either the NaCl-resistant spontaneously hypertensive rat (SHR-R) or the normotensive Wistar-Kyoto (WKY) rat. In the current study, the effect of dietary NaCl supplementation on arterial baroreceptor reflex control of lumbar sympathetic nerve activity and heart rate was assessed in SHR-S and control SHR-R and WKY rats. Male SHR-S, SHR-R, and WKY rats were fed diets containing either 1% or 8% NaCl beginning at 7 weeks of age and were studied at age 9-10 weeks. Arterial baroreceptor reflex-mediated changes in lumbar sympathetic nerve activity and heart rate were recorded in conscious, unrestrained rats during phenylephrine-induced (15-40 micrograms/kg/min) and nitroprusside-induced (15-300 micrograms/kg/min) changes in mean arterial pressure. SHR-S maintained on a 1% NaCl diet had blunted baroreceptor reflex control of lumbar sympathetic nerve activity during acute increases in MAP compared with SHR-R and WKY rats (p less than 0.05). After ingestion of the 8% NaCl diet, this blunting was absent, indicating enhancement of baroreceptor reflex control of lumbar sympathetic nerve activity. SHR-S maintained on a 1% NaCl diet also had blunted arterial baroreceptor control of lumbar sympathetic nerve activity during nitroprusside-induced decreases in mean arterial pressure compared with WKY rats, but this was not significantly altered during ingestion of the 8% NaCl diet.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fabry disease: isolation of a cDNA clone encoding human alpha-galactosidase A.

Fabry disease is an X-linked inborn error of metabolism resulting from the deficient activity of the lysosomal hydrolase, alpha-galactosidase A (alpha-Gal A; alpha-D-galactoside galactohydrolase, EC 3.2.1.22). To investigate the structure, organization, and expression of alpha-Gal A, as well as the nature of mutations in Fabry disease, a clone encoding human alpha-Gal A was isolated from a lambda gt11 human liver cDNA expression library. To facilitate screening, an improved affinity purification procedure was used to obtain sufficient homogeneous enzyme for production of monospecific antibodies and for amino-terminal and peptide microsequencing. On the basis of an amino-terminal sequence of 24 residues, two sets of oligonucleotide mixtures were synthesized corresponding to adjacent, but not overlapping, amino acid sequences. In addition, an oligonucleotide mixture was synthesized based on a sequence derived from an alpha-Gal A internal tryptic peptide isolated by reversed-phase HPLC. Four positive clones were initially identified by antibody screening of 1.4 X 10(7) plaques. Of these, only one clone (designated lambda AG18) demonstrated both antibody binding specificity by competition studies using homogeneous enzyme and specific hybridization to synthetic oligonucleotide mixtures corresponding to amino-terminal and internal amino acid sequences. Nucleotide sequencing of the 5' end of the 1250-base-pair EcoRI insert of clone lambda AG18 revealed an exact correspondence between the predicted and known amino-terminal amino acid sequence. The insert of clone lambda AG18 appears to contain the full-length coding region of the processed, enzymatically active alpha-Gal A, as well as sequences coding for five amino acids of the amino-terminal propeptide, which is posttranslationally cleaved during enzyme maturation.     

Validity of plasma aldosterone-to-renin activity ratio in African American and white subjects with resistant hypertension

BACKGROUND: Recent reports suggesting that primary aldosteronism (PA) is more common than historically thought have often relied on use of the plasma aldosterone concentration (PAC) to plasma renin activity (PRA) ratio (ARR) to identify patients with PA. Prior determinations of the validity of the ARR had been generally limited to subjects that could be withdrawn from antihypertensive therapy and to non-African American subjects. METHODS AND RESULTS: The current study was designed to evaluate prospectively the diagnostic value of the ARR in treated African American and white subjects with resistant hypertension. Consecutive subjects referred to a university hypertension clinic for resistant hypertension were evaluated with an early morning ARR and a 24-h urinary aldosterone and sodium. The presence of PA was defined as a suppressed PRA (<1.0 ng/mL/h) and elevated urinary aldosterone excretion (>12 microg/24 h) during high dietary sodium ingestion (>200 mEq/24 h). In 58 subjects, PA was confirmed. The ARR was elevated (>20) in 45 of 58 subjects with PA and in 35 of the 207 patients without PA, resulting in a sensitivity of 78% and specificity of 83% with a corresponding positive predictive value of 56% and a negative predictive value of 93%. Among African American subjects, the ARR was less sensitive than in white subjects (75% v 80%), but it still had a high negative predictive value (92% v 94%). CONCLUSIONS: These data indicate that the ARR is valid as a screening test for PA in African American and white patients on stable antihypertensive treatments, but a high percentage of false-positive results precludes using it for accurate diagnosis of PA.     

Brain connectivity during verbal working memory in children and adolescents

Working memory (WkM) is a fundamental cognitive process that serves as a building block for higher order cognitive functions. While studies have shown that children and adolescents utilize similar brain regions during verbal WkM, there have been few studies that evaluate the developmental differences in brain connectivity. Our goal was to study the development of brain connectivity related to verbal WkM in typically developing children and adolescents. Thirty‐five healthy children and adolescents, divided into three groups: 9–12 (children), 13–16 (young adolescents), and 17–19 (older adolescents) years, were included in this functional magnetic resonance imaging (fMRI) study. The verbal WkM task involved a modified Sternberg item recognition paradigm using three different loads. Brain connectivity analysis was performed using independent component analyses and regressing the components with the design matrix to determine task‐related networks. Connectivity analyses resulted in four components associated solely with encoding, four solely with recognition and two with both. Two networks demonstrated age‐related differences with respect to load, (1) the left motor area and right cerebellum, and 2) the left prefrontal cortex, left parietal lobe, and right cerebellum. Post hoc analyses revealed that the first network showed significant effects of age between children and the two older groups. There was increasing connectivity with increasing load for adolescents. The second network demonstrated age‐related differences between children and older adolescents. Children have higher task‐related connectivity at lower loads, but they tend to equalize with the adolescents with higher loads. Finally, a non‐load related network involving the orbital frontal and anterior cingulate cortices showed less connectivity in children. Hum Brain Mapp 35:698–711, 2014. © 2012 Wiley Periodicals, Inc.