Suppression of programmed cell death by intracellular cAMP is not mediated by expression of genes encoding an inhibitor of apoptosis.

The elevation of intracellular cAMP content is accompanied by expression of genes whose promoter contains a Ca(2+)-cAMP responsive element. In vascular smooth muscle cells (VSMC), activation of cAMP signaling blocks apoptosis triggered by serum deprivation. In the present study we investigated the role of gene expression in the inhibition of apoptosis by cAMP.

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.

The alpha1-Na/K pump does not mediate the involvement of ouabain in the development of hypertension in rats.

The Na/K pump of vascular smooth muscle cells (VSMC) and renal epithelial cells (REC) is viewed as a target of digitalis and endogenous ouabain (EO), leading to the development of hypertension. In this study, we compared the effect of ouabain on Na/K pump activity and the intracellular content of monovalent cations in VSMC and REC obtained from rats, humans and dogs. In VSMC from the rat aorta, ouabain inhibited maximal Na/K pump activity measured as the rate of 86Rb influx in Na+-loaded cells, with an ID50 of approximately 20-30 microM without any differences between two strains of normotensive rats (WKY and BN.

Congenic mapping of a blood pressure QTL on chromosome 16 of Dahl rats.

A Chromosome (Chr) 16 segment of the Dahl salt-sensitive (S) rat was shown by linkage to contain a blood pressure (BP) quantitative trait locus (QTL). To verify and further narrow down the region harboring the QTL, we made two congenic strains by replacing two segments of the S rats with the homologous segments of the Lewis (LEW) rats. The construction of these congenic strains was facilitated by a genome-wide marker screening.

Apoptosis in cardiovascular remodeling--effect of medication.

In the last decade, apoptosis has emerged as a key determinant of target organ damage in cardiovascular diseases. The suggestion that increased cardiomyocyte apoptosis participates in the etiology of heart failure probably contributed to the negative view of the prevalence of apoptosis in the field of cardiovascular diseases. However, we and others have shown that up-regulation of apoptosis in certain cardiovascular cells may contribute to the beneficial action of antihypertensive drugs on target-organ structure.

Genetics of programmed cell death and proliferation.

Vascular remodeling and hypertrophy-hyperplasia of the heart and kidney are the hallmarks of hypertensions, being involved in the long-term maintenance of elevated blood pressure and the development of cardiovascular and renal hypertension. Both augmented proliferation and unscheduled programmed cell death (apoptosis) contribute to this phenomenon. In the present article, we summarize the results of these studies with an emphasis on the relative impact of genetic determinants and the environment.

Chromosomal mapping of HCaRG, a novel hypertension-related, calcium-regulated gene.

We recently identified a novel gene that is negatively regulated by extracellular calcium concentration with higher levels of transcripts in hypertensive animals (SHR). We named this gene HCaRG (Hypertension-related, Calcium-Regulated Gene). In this work we report the chromosomal localization of the HCaRG gene among different species.

Swelling-induced K(+) fluxes in vascular smooth muscle cells are mediated by charybdotoxin-sensitive K(+) channels.

This study examines the relative contributions of K-Cl cotransport and K(+) channels to swelling-induced K(+) fluxes in vascular smooth muscle cells (VSMC). DIOA known as a potent inhibitor of erythrocyte K-Cl cotransport exerts diverse side-effects on VSMC and can not be used to analyze the role of this carrier in swelling-induced K(+) fluxes. Other inhibitors of K-Cl cotransport (furosemide, okadaic acid and calyculin A) did not affect K(+) fluxes in VSMC triggered by swelling.

Identification and chromosomal localization of ecogenetic components of electrolyte excretion.

Objective: To determine to what extent urinary excretion of blood pressure-modulating electrolytes is genetically determined, and to identify their chromosomal localization.

Design And Methods: Twenty-six rat recombinant inbred strains (RIS) originating from reciprocal crosses of normotensive Brown Norway (BN.Lx) and spontaneously hypertensive rats (SHR) were used.

Replacement of (alpha)1-Na-K-ATPase of Dahl rats by Milan rats lowers blood pressure but does not affect its activity.

Both linkage and use of congenic strains have shown that a chromosome region near the gene for the Na-K-ATPase alpha(1)-subunit (Atp1a1) contained a quantitative trait locus (QTL) for blood pressure (BP). Currently, two congenic strains, designated S.M5 and S.

AVAPROMISE: A randomized clinical trial for increasing adherence through behavioural modification in essential hypertension.

Background: Patients with hypertension often do not adhere to their medications.

Objective: To improve medication adherence in patients with essential hypertension by modifying their behaviours.

Patients And Methods: From general practice settings, 4864 patients with essential hypertension were recruited and randomly assigned to receive the angiotensin receptor blocker irbesartan (Avapro) with (intervention group) or without (nonintervention group) a behavioural modification program (Avapromise) based on a model of change.

Distribution of blood pressure and hypertension in Canada and the United States.

Background: Two North American population based surveys, the Third National Health and Nutrition Examination Survey (NHANES III) and the Canadian Heart Health Surveys (CHHS) have similar time frames and methods that allow comparisons between these countries in terms of the distribution of systolic (SBP) and diastolic (DBP) blood pressure and the levels of hypertension awareness, treatment, and control.

Methods: Cross-sectional population surveys using similar methods conducted home interviews and clinic visits (CHHS), and medical examinations (NHANES III). The CHHS included the ten Canadian provinces (1986-1992) and NHANES III, a representative sample of the United States population (1988-1994).

Aberrant membrane hormone receptors in incidentally discovered bilateral macronodular adrenal hyperplasia with subclinical Cushing's syndrome.

Cortisol secretion in adrenal Cushing's syndrome can be regulated by the aberrant adrenal expression of receptors for gastric inhibitory polypeptide, vasopressin, catecholamines, LH/human CG (LH/hCG), or serotonin. Four patients with incidentally discovered bilateral macronodular adrenal hyperplasia without clinical Cushing's syndrome were evaluated for the possible presence of aberrant adrenocortical hormone receptors. Urinary free cortisol levels were within normal limits, but plasma cortisol levels were slightly elevated at nighttime and suppressed incompletely after dexamethasone administration.

The angiotensin II type 1 receptor and receptor-associated proteins.

The mechanisms of regulation, activation and signal transduction of the angiotensin II (Ang II) type 1 (AT1) receptor have been studied extensively in the decade after its cloning. The AT1 receptor is a major component of the renin-angiotensin system (RAS). It mediates the classical biological actions of Ang II.

Predictors of target organ damage in hypertensive blacks and whites.

The purpose of this study was to evaluate the association of the insulin resistance syndrome with both blood pressure and target organ damage in blacks and whites with essential hypertension. Eighty-two black and 63 white French Canadian patients were studied. None had diabetes, and antihypertensive medications had been discontinued for >/=1 week.

Evidence of an altered in vivo vascular cell turnover in spontaneously hypertensive rats and its modulation by long-term antihypertensive treatment.

The aims of this study were to measure in vivo cell turnover in the thoracic aorta from spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) and to investigate how it could be modulated by chronic antihypertensive treatment. Cell turnover was estimated in rats in which DNA had been prelabeled in utero with [ 3 H]-thymidine, by the rate of disappearance of total [ 3 H]-DNA from birth to 20 weeks of age. In SHR compared with WKY, neonatal relative aortic mass was transiently elevated and was reversed to hypotrophy at 8 weeks.

Inhibition of Na+,K+ pump affects nucleic acid synthesis and smooth muscle cell proliferation via elevation of the [Na+]i/[K+]i ratio: possible implication in vascular remodelling.

Objectives: Na+,K+ pump inhibition is known to delay the development of apoptosis in vascular smooth muscle cells (VSMC). This study examines Na+,K+ pump involvement in the regulation of VSMC macromolecular synthesis and proliferation.

Methods: DNA, RNA and protein synthesis in VSMC from the rat aorta was studied by the incorporation of [3H]-labelled thymidine, uridine and leucine.

Regression of neointimal lesions in the carotid artery of nifedipine-treated SHR and WKY rats: possible role of apoptosis.

We previously observed that nifedipine reduces aortic hypertrophy in spontaneously hypertensive rats (SHR) partly by inducing smooth muscle cell (SMC) apoptosis. The present study examined nifedipine regulation of SMC apoptosis in carotids with or without a neointima. A neointima was produced by endothelial denudation of the left carotid of SHR and WKY rats.

Longitudinal analysis of motor activity and coordination, anxiety, and spatial learning in mice with altered blood pressure.

Mice with either high or low blood pressure (BP) were compared to normotensive controls at 2 and 12 months of age for motor activity, equilibrium, anxiety, and spatial learning. Irrespective of age, high BP mice were more active in an open field than normotensive controls, whereas low BP mice were hypoactive at 2 months of age. High BP mice had a higher number of entries and a longer duration of visits in the open arms, a higher open arm/total arm ratio, a longer duration for the first visit into an open arm, and lower latencies before entering the first open arm than controls in the elevated +-maze, indicative of reduced anxiety.

Heritability estimates of obesity measures in siblings with and without hypertension.

The goal of the present study was to evaluate mean values and heritability estimates of 3 global and 11 regional obesity measures in siblings with (HPT, n=209) or without (non-HPT, n=91) early-onset (age View Article and Find Full Text PDF

In vivo variability of TMA oxidation is partially mediated by polymorphisms of the FMO3 gene.

Trimethylaminuria (TMAU) results from an accumulation of an excessive amount of unoxidized trimethylamine that is excreted in urine and body secretions. Mutations of the flavin-containing monooxygenase 3 (FMO3) gene (a hepatic phase I drug-metabolizing enzyme) account for the severe recessively encoded form of this condition. We have previously described a number of FMO3 polymorphisms which in vitro exhibit reduced substrate affinity for several FMO substrates.

Antiproliferative effect of brief exposure to cholera toxin in vascular smooth muscle cells: role of cAMP and protein kinase A.

The effect of cholera toxin (CTX), an activator of the adenylate cyclase-coupled G protein alpha(s) subunit, was studied on cultured vascular smooth muscle cell (VSMC) proliferation. Continuous exposure (48 h) to CTX as well as 2-min pretreatment of VSMC with CTX led to the same level of cAMP production, inhibition of DNA synthesis, and arrest in the G1 phase without induction of necrosis or apoptosis in VSMC. Protein kinase A (PKA) activity in CTX-pretreated cells was transiently elevated by 3-fold after 3 h of incubation, whereas after 48 h it was reduced by 2-fold compared with baseline values without modulation of the expression of its catalytic alpha subunit.

Endothelial and myocyte apoptosis--role of angiotensin II.

Recent studies have assessed the role of angiotensin II in apoptosis and the effects of the angiotensin II type 1 (AT1) and type 2 (AT2) receptor subtypes. A complex picture is emerging with cell-specific effects of AT1 and AT2 receptors, and differential effects dependent on pathology. In vitro studies have shown that angiotensin II mediated apoptosis in myocytes and endothelium.

The 2000 Canadian recommendations for the management of hypertension: Part one--therapy.

Objective: To provide updated, evidence-based recommendations for the therapy of hypertension in adults.

Options: For patients with hypertension, there are a number of lifestyle manoeuvres and antihypertensive agents that 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.

Morphology of renal afferent arterioles and glomeruli, heart weight, and blood pressure in primates.

In a Caribbean outbred population of African green monkeys (Cercopithecus aethiops), 5 to 10% of feral adults have elevated blood pressure (BP). We have investigated whether the increased pressure is associated with abnormal renal afferent arteriole structure or glomerular number. In seven young adult (aged 7 to 13 years) male monkeys with consistently high BP (mean BP, 111 mm Hg; ketamine anesthesia) and seven controls (mean BP, 81 mm Hg), the morphology of the renal vasculature has been analyzed in three cortical zones.