Decreased NKCC1 activity in erythrocytes from African Americans with hypertension and dyslipidemia.

Background: Recent studies demonstrated a key role of ubiquitous isoform of Na+,K+,2Cl- co-transport (NKCC1) in regulation of myogenic tone and peripheral resistance. We examined the impact of race, gender, and plasma lipid on NKCC1 activity in French Canadians and African Americans with hypertension and dyslipidemia.

Methods: NKCC and passive erythrocyte membrane permeability to K+, measured as ouabain-resistant, bumetanide-sensitive, and (ouabain+bumetanide)-resistant 86Rb influx, respectively, were compared in 111 French-Canadian men, 107 French-Canadian women, 26 African-American men, and 45 African-American women with essential hypertension and dyslipidemia.

When is knowledge ripe for primary care? An exploratory study on the meaning of evidence.

The objectives of this study were to explore the meaning of scientific evidence as it is understood by primary care physicians. Individual interviews were conducted with actors chosen for their roles in the production and use of knowledge: 22 family physicians, 13 specialist physicians, and 6 researchers. Two situations served as points of reference for these discussions: screening for genetic breast cancer and treatment of hypertension.

Genome-wide scan for linkage to obesity-associated hypertension in French Canadians.

Essential hypertension is a heterogeneous disorder that is thought to develop because of several overlapping subsets of underlying mechanisms. One such causal pathway may involve pathophysiological alterations induced by obesity. In the present study, we examined whether investigating clinically defined subtypes of hypertension, such as obesity-associated hypertension, facilitates the search for its genes.

Characterization of a cGMP-response element in the guanylyl cyclase/natriuretic peptide receptor A gene promoter.

Previous studies have shown that atrial natriuretic peptide (ANP) can inhibit transcription of its receptor, guanylyl cyclase A, by a mechanism dependent on cGMP and have suggested the presence of a putative cGMP-response element (cGMP-RE) in the Npr1 gene promoter. To localize and characterize the putative cis-acting element, we have subcloned a 1520-bp fragment of the rat Npr1 promoter in an expression vector containing the luciferase reporter gene. Several fragments, generated by exonuclease III-directed deletions, were transiently transfected into cells to measure their promoter activity.

TA repeat variation, Npr1 expression, and blood pressure: impact of the Ace locus.

The activity of the atrial natriuretic peptide receptor (Npr1) is altered in spontaneously hypertensive rats (SHR) in relation to its mRNA levels, suggesting abnormal transcriptional control in hypertension. A single-stranded conformational polymorphism caused by a repetitive dinucleotide segment of 10 TA in BN-Lx and of 40 TA in SHR was localized at position -943 relative to the transcription start site of the Npr1 gene, downstream of a putative cGMP-regulatory region, and was the only sequence difference noted between the two strains. Transient transfections of -1520 to -920 Npr1 promoter-SV40-luciferase fusion vector showed that the construct from BN-Lx stimulated the SV40 promoter, whereas that from SHR slightly inhibited it.

A genealogical study of essential hypertension with and without obesity in French Canadians.

Objectives: To investigate genetic homogeneity in a set of hypertensive families and in subsets chosen for high and low prevalence of obesity; and to compare fasting insulin and lipids, ion transport, and water homeostasis in the obese and lean families.

Research Methods And Procedures: The study was carried out in a relative population isolate of the Saguenay/Lac St. Jean region in Canada.