Apolipoprotein E alleles and hypertension: controversy or lack of understanding?
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Alleles↗
Biomedical subjects
Pavel Hamet
Publications and source records attributed to Pavel Hamet.
Identification of hypertension-related QTLs in African American sib pairs.
To link hypertension-related phenotypes with chromosomal loci, genome scans were performed in 150 African American sib pairs concordant for essential hypertension. Phenotypes included blood pressure, anthropomorphic measurements, and estimates of body fluid compartments as determined by impedance plethysmography. These phenotypes were also measured in 335 normotensive African Americans. Phenotypes with LOD scores >3.3 were further evaluated for significance by use of permutation procedures. Significant linkage was detected for body mass index (BMI) on chromosomes 1 and 8 and for the ratio of extracellular water to total body water (ECF/TBW) on chromosomes 3, 5, 6, and 7. Both BMI and ECF/TBW were greater in hypertensive sibs than in normotensive subjects (P<0.001). In a subset of hypertensive sibs and normotensive subjects, average 24-hour blood pressures were correlated with ECF/TBW (P<0.01). A region linked to BMI in the hypertensive sibs corresponds to a region of conserved synteny containing blood pressure-related QTLs in an F2 cross of Brown NorwayxDahl salt-sensitive rats. Focusing on hypertension-related phenotypes is a promising approach for identifying the genetic determinants of hypertension.
Adolescent↗
Biochemistry and physiology of the natriuretic peptide receptor guanylyl cyclases.
Guanylyl cyclases (GC) exist as soluble and particulate, membrane-associated enzymes which catalyse the conversion of GTP to cGMP, an intracellular signalling molecule. Several membrane forms of the enzyme have been identified up to now. Some of them serve as receptors for the natriuretic peptides, a family of peptides which includes atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP), three peptides known to play important roles in renal and cardiovascular physiology. These are transmembrane proteins composed of a single transmembrane domain, a variable extracellular natriuretic peptide-binding domain, and a more conserved intracellular kinase homology domain (KHD) and catalytic domain. GC-A, the receptor for ANP and BNP, also named natriuretic peptide receptor-A or -1 (NPR-A or NPR- 1), has been studied widely. Its mode of activation by peptide ligands and mechanisms of regulation serve as prototypes for understanding the function of other particulate GC. Activation of this enzyme by its ligand is a complex process requiring oligomerization, ligand binding, KHD phosphorylation and ATP binding. Gene knockout and genetic segregation studies have provided strong evidence for the importance of GC-A in the regulation of blood pressure and heart and renal functions. GC-B is the main receptor for CNP, the latter having a more paracrine role at the vascular and venous levels. The structure and regulation of GC-B is similar to that of GC-A. This chapter reviews the structure and roles of GC-A and GC-B in blood pressure regulation and cardiac and renal pathophysiology.
Animals↗
The 2001 Canadian recommendations for the management of hypertension: Part two--Therapy.
OBJECTIVE: To provide updated, evidence-based recommendations for the therapy of hypertension in adults. OPTIONS: For patients with hypertension, a number of antihypertensive agents may control blood pressure. Randomized trials evaluating first-line therapy with thiazides, beta-adrenergic antagonists, angiotensin-converting enzyme inhibitors, calcium channel blockers, alpha-blockers, centrally acting agents or angiotensin II receptor antagonists were reviewed. OUTCOMES: The health outcomes that were considered were changes in blood pressure, cardiovascular morbidity, and cardiovascular and/or all-cause mortality rates. Economic outcomes were not considered due to insufficient evidence. EVIDENCE: MEDLINE was searched for the period March 1999 to October 2001 to identify studies not included in the 2000 revision of the Canadian Recommendations for the Management of Hypertension. Reference lists were scanned, experts were polled, and the personal files of the subgroup members and authors were used to identify other published studies. All relevant articles were reviewed and appraised, using prespecified levels of evidence, by content experts and methodological experts. VALUES: A high value was placed on the avoidance of cardiovascular morbidity and mortality. BENEFITS, HARMS AND COSTS: Various antihypertensive agents reduce the blood pressure of patients with sustained hypertension. In certain settings, and for specific classes of drugs, blood-pressure lowering has been associated with reduced cardiovascular morbidity and/or mortality. RECOMMENDATIONS: The present document contains detailed recommendations pertaining to treatment thresholds, target blood pressures, and choice of agents in various settings in patients with hypertension. The main changes from the 2000 Recommendations are the addition of a section on the treatment of hypertension in patients with diabetes mellitus, the amalgamation of the previous sections on treatment of hypertension in the young and old into one section, increased emphasis on the role of combination therapies over repeated trials of single agents and expansion of the section on the treatment of hypertension after stroke. Implicit in the recommendations for therapy is the principle that treatment for an individual patient should take into consideration global cardiovascular risk, the presence and/or absence of target organ damage, and comorbidities. VALIDATION: All recommendations were graded according to strength of the evidence and voted on by the Canadian Hypertension Recommendations Working Group. Individuals with potential conflicts of interest relative to any specific recommendation were excluded from voting on that recommendation. Only those recommendations achieving high levels of consensus are reported here. These guidelines will continue to be updated annually.
Antihypertensive Agents↗