Biomedical subjects

P Hamet

Publications and source records attributed to P Hamet.

At least 37 records · Page 2Linked to original sources

PubMed2001

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.M6, were made by replacing a segment of the Dahl salt-sensitive SS/Jr (S) rat by the homologous region of the Milan normotensive rat (MNS). In S.M5, the gene for Atp1a1 is from the MNS strain; whereas in S.M6, Atp1a1 is from the S strain. The baseline activity of the alpha(1)-Na-K-ATPase and its stoichiometry were evaluated by an assay of ouabain-sensitive inwardly and outwardly directed (86)Rb and (22)Na fluxes in erythrocytes. The two congenic strains showed a similar BP, but both had a BP lower than that of S rats (P < 0.0001). Neither the alpha(1)-Na-K-ATPase activity nor its stoichiometry was affected by the substitution of the Atp1a1 alleles of S by those of MNS. Thus the BP-lowering effects observed in S.M5 and S.M6 could not be attributed to the alpha(1)-Na-K-ATPase activity or its stoichiometry. Atp1a1 is not supported as a candidate to be a BP QTL.

Alleles↗

PubMed2001

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. Reduced levels of anxiety were also displayed by low BP mice for the duration of the first open arm visit (both age groups) and for the time spent in the open arms (older group). In the motor coordination test (coat-hanger), high BP mice had higher two-paw movement time and reached the top of the apparatus on fewer occasions than controls. Both groups with abnormal BP values were deficient during visuomotor guidance in the water maze. These results indicate strain-, age-, and test-specific abnormalities in mice with uncontrolled hypertension or hypotension.

Aging↗

PubMed2001

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. Here we show that three prevalent polymorphisms (E158K, V257M, and E308G) inherited in particular combinations confer a slight decrease in TMA oxidation under normal physiological conditions, which may be clinically "silent." With the use of substrate loading or with the interaction of other known modulators of FMO3 activity such as hormonal influences, these genotypes may predispose to mild TMAU.

Alleles↗

PubMed2001

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. In each animal, the left kidney vasculature was fixed while relaxed and at known intravascular pressure, and afferent arteriolar diameter and media cross-sectional area were estimated. The right kidney was perfusion-fixed and prepared for unbiased stereologic estimation of glomerular number and size. No difference was found in afferent arteriole lumen diameter or media cross-sectional area, or in glomerular number or size, between the high BP group and controls. There was no difference in heart weight between the two groups, but there was a negative correlation between left ventricle heart weight and afferent arteriole diameter (controls: r = -0.81, P = .025; all animals: r = -0.70, P = .005, slope about 3.5% reduction in lumen diameter for 10% increase in heart weight). The results suggest that cardiac mass and renal afferent arteriole structure may be controlled by a common mechanism unrelated to BP measured in anesthesia. However, the lack of conscious measurements prevents conclusions as to whether this mechanism involves ambulatory BP.

Animals↗

PubMed2001

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). Blood pressure measurements were available for 23,111 Canadians (age 18-74 years), and restricted to the 15,326 US participants in the same age range (age 18-74 years) with both systolic and diastolic mean values. Standardized techniques were used for BP measurements. Mean of all available measurements was used from four measurements for the CHHS and six measurements for NHANES III. A mean SBP/DBP of 140/90 mm Hg or treated with medication defined hypertension. All measures were weighted to represent population values. RESULTS: Both surveys showed similar trends in mean BP by age, with slightly higher levels in the CHHS. Hypertension prevalence using the same definitions and the same age range (18-74 years) was NHANES III: 20.1%, CHHS: 21.1%. Although the prevalence of isolated systolic hypertension (ISH) was similar in both studies, around 8% to 9%, the CHHS had higher ISH prevalence than NHANES III in the younger age groups and lower prevalence in the older age groups. Elevated SBP dominated the prevalence figures after the 1950s in both studies. Compared to NHANES III, the CHHS showed a lower proportion (43% v 50%) of individuals with optimal BP (< 120/80 mm Hg) and a very low proportion of hypertensives under control (13% v 25%). About half of diabetic participants were hypertensive (using 140/90 mm Hg) in both countries with a very low level of control in Canada (9%) v the US (36%) for ages 18 to 74 years. CONCLUSIONS: The results of these two surveys highlight the importance of SBP, in the later decades of life, an overall low control of hypertension in both countries, and a better overall awareness, treatment, and control of hypertension in the US than in Canada for that period. Dissemination of hypertension guidelines and a more aggressive focus on SBP are urgently needed in Canada, with special attention to diabetics.

Adult↗

PubMed2001

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. As an explanation for this apparent discrepancy, the same stimulus, e.g. angiotensin II, can induce apoptosis or stimulate cell growth in different cell types (e.g., cardiomyocytes and fibroblasts, respectively). Using the angiotensin pathway as a paradigm, this review proposes an integrative view of cell growth and cell death regulation in cardiovascular cells in order to illustrate how cell-specific responses to the same stimulus may in part explain the patterns of cell population dynamics during the development and treatment of target organ damage in hypertension.

Angiotensin Receptor Antagonists↗

PubMed2001

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. Among the structures required for regulation and activation of the receptor, its carboxyl-terminal region plays crucial roles in receptor internalization, desensitization and phosphorylation. The mechanisms involved in heterotrimeric G-protein coupling to the receptor, activation of the downstream signaling pathway by G proteins and the Ang II signal transduction pathways leading to specific cellular responses are discussed. In addition, recent work on the identification and characterization of novel proteins associated with carboxyl-terminus of the AT1 receptor is presented. These novel proteins will advance our understanding of how the receptor is internalized and recycled as they provide molecular mechanisms for the activation and regulation of G-protein-coupled receptors.

Adaptor Proteins, Signal Transducing↗

PubMed2001

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. Cell cycle progression was estimated by flow cytometry. Intracellular Na+ and K+ content and Na+,K+ pump activity were quantified as the steady-state distribution of 22Na and 86Rb and the rate of ouabain-sensitive 86Rb uptake in Na+-loaded cells, respectively. RESULTS: Ouabain inhibited the Na+,K+ pump with a Ki of 0.1 mmol/l. At concentrations less than 0.1 mmol/l, neither [Na+]i nor [K+]i was affected by ouabain; elevation of ouabain concentration sharply increased the [Na+]i/[K+]i ratio with a K0.5 of approximately 0.3 mmol/l. At concentrations higher than 0.1 mmol/l, ouabain time- and dose-dependently activated RNA and DNA syntheses in serum-deprived VSMC and inhibited cell cycle progression triggered by serum. In quiescent VSMC, ouabain did not affect protein synthesis, total cell number, but slightly increased the percentage of cells in the S-phase (4.25 versus 1.46%) and attenuated cell death assessed by staining with trypan blue and lactate dehydrogenase release. CONCLUSIONS: Elevation of the [Na+]i/[K+]i ratio caused by Na+,K+ pump inhibition markedly enhances nucleic acid synthesis in quiescent VSMC and blocks cell cycle progression in serum-supplied VSMC. The relative contribution of this phenomenon as well as the anti-apoptotic action of increased [Na+]i/[K+]i ratio to vascular remodelling under augmented content of endogenous Na+,K+ pump inhibitors, seen in volume-expanded hypertension, should be investigated by in-vivo studies.

Animals↗

PubMed2001

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. At 20 weeks of age, aortic hypertrophy reappeared. Aortic DNA content reflected the morphologic changes observed with age. In both SHR and WKY, the decline with time in [ 3 H]-prelabeled aortic DNA coupled with the increase in total organ DNA demonstrated that cells prelabeled in utero died and were replaced. Decline in [ 3 H]-DNA from birth to 8 weeks of age was approximately threefold faster in the aorta from SHR than in WKY. In older SHR, the decrease in [ 3 H]-DNA was then slower and similar to that of WKY. Chronic treatment of SHR for 15 weeks from the age of 5 weeks, with hydralazine, enalapril, or nifedipine prevented the rise in systolic blood pressure, aortic mass, and DNA content. This was associated with an unchanged residual radioactivity of [ 3 H]-prelabeled aortic DNA over time, suggesting that the treatment did not stimulate cumulative cell death. We propose that the altered cell turnover is a component of aortic remodeling observed in hypertension. Our data also suggest that it is possible to modulate in vivo cell turnover and affect vascular remodeling by pharmacologic therapy.

Age Factors↗

PubMed2001

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. Swelling-induced K(+) fluxes in VSMC were also not affected by K(+) channel blockers such as TEA, glibenclamide and apamin, but were blocked by Ba(2+) and charybdotoxin (ChTX), a potent inhibitor of Ca(2+)- and voltage-gated K(+) channels. Swelling-induced K(+) influx in VSMC was diminished in Ca(2+)-free medium and in cells loaded with Ca(2+) chelator BAPTA, but was not accompanied by detectable elevation of [Ca(2+)](i). In contrast to Ca(2+)-induced hyperpolarization of erythrocytes triggered by activation of intermediate conductance Ca(2+)-gated K(+) channels (IK(Ca)), neither clotrimazole nor calmodulin antagonists (R24571, trifluoroperazine, fluphenazine) affected swelling-induced K(+) influx in VSMC. In conclusion, K(+) fluxes triggered in swollen VSMC are mediated by Ba(2+)- and ChTX-sensitive K(+) channels. These channels are distinct from IK(Ca) expressed in erythrocytes. Their molecular origin and systems involved in the swelling-induced Ca(2+)(i)-independent signal transduction pathway need further investigation.

Animals↗

PubMed2001

Workshop: excess growth and apoptosis: is hypertension a case of accelerated aging of cardiovascular cells?

Several groups including ours have demonstrated cardiac hyperplasia in neonates from genetically hypertensive rat strains. We have shown that similar problems exist in the kidney as well. More recently, we found that excessive heart and kidney weight is neonatally related to inhibition of apoptosis. Using recombinant inbred strains derived from a reciprocal cross between Brown Norway and spontaneously hypertensive rat progenitor strains, we mapped the inhibition of neonatal apoptosis to 2 distinct loci on chromosomes 1 (Myl 2) and 18 (Abrb 2). Positional candidate genes at these loci are being explored. These studies have also demonstrated that the loci determining kidney and heart weights in neonates are distinct from those determining increased organ weight in adults. The impact of blood pressure per se is also divergent because adult kidney weight is negatively correlated whereas heart weight is positively correlated with it. Analyses by extremes of low and high percentiles from fetal life to adulthood identified a single locus determining heart weight at Acaa on chromosome 8 in newborn (P=0.0003) and adult (P=0.016) rats. The Acaa region contains a DNA mismatch repair gene (hMLH1). The kinetics of neonatal growth through adulthood by prelabeling DNA with [(3)H]thymidine in pregnant mares showed that although the growth process is complex and nonlinear in the kidney of hypertensive rats, there is an increased turnover of cells, that is, reduced half-life of DNA. This observation is supported by the presence of shorter telomere fragments in kidneys of spontaneously hypertensive rats. These studies suggest that cardiovascular cells from hypertensive animals are subject to accelerated turnover, potentially leading to their accelerated aging.

Animals↗

PubMed2001

Arterial pressure, left ventricular mass, and aldosterone in essential hypertension.

The purpose of the present study was to evaluate the relationship of aldosterone to blood pressure and left ventricular size in black American (n=109) and white French Canadian (n=73) patients with essential hypertension. Measurements were obtained with patients off antihypertensive medications and included 24-hour blood pressure monitoring, plasma renin activity and aldosterone, and an echocardiogram. Compared with the French Canadians, the black Americans had higher body mass indexes, higher systolic blood pressures, attenuated nighttime reduction of blood pressure, and lower serum potassium concentrations (P:<0.01 for each). Left ventricular mass index, posterior wall thickness, interventricular septal thickness, and relative wall thickness were also greater (P:<0.01 for each) in the black American patients. Supine and standing plasma renin activity was lower (P:<0.01 and P:<0.05, respectively) in the black Americans, whereas supine plasma aldosterone concentrations did not differ, and standing plasma aldosterone was greater (P:<0.05) in the black Americans (9.2+/-0.7 ng/dL) than in the French Canadians (7.3+/-0.6 ng/dL). In the black Americans, supine plasma aldosterone was positively correlated with nighttime systolic (r=0.30; P:<0.01) and diastolic (r=0.39; P:<0.001) blood pressures and inversely correlated with the nocturnal decline of systolic (r=-0.29; P:<0.01) and diastolic (r=-0.37; P:<0.001) blood pressures. In the black Americans, standing plasma aldosterone was positively correlated with left ventricular mass index (r=0.36; P:<0.001), posterior wall thickness (r=0.33; P:<0.01), and interventricular septal thickness (r=0.26; P:<0.05). When the black American patients were divided into obese and nonobese groups, significant correlations between plasma aldosterone and both blood pressure and cardiac mass were observed only in the obese. In the French Canadians, overall, plasma aldosterone did not correlate with either blood pressure or any measures of heart size. However, among obese French Canadians, supine plasma aldosterone correlated with nighttime diastolic (r=0.53, P:<0.02) and systolic (r=0.44, P:<0.01) blood pressures but not with cardiac mass. These results are consistent with the hypothesis that aldosterone contributes to elevated arterial pressure in obese black American and obese white French Canadian patients with essential hypertension and to the attenuated nocturnal decline of blood pressure and left ventricular hypertrophy in obese, hypertensive black Americans.

Adult↗

PubMed2001

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 </=55 years) hypertension who originated from the same families. Sixty-one sibships, each having at least 2 HPT siblings, were selected from a French-Canadian population with a known founder effect. Comparison of the mean values showed that HPT siblings are more obese than non-HPT siblings and that the body fat of HPT siblings is more centrally distributed. Significant differences were observed in all global obesity measures (P=0.009 to 0.0001). Among the regional measures, the most prominent differences were seen in waist circumference (P=0.00002), waist/hip ratio (P=0.0001), and suprailiac skinfold (P=0.00008). Comparison of the heritability estimates derived from sibling/sibling correlations (FCOR program, SAGE) suggested that genetic factors play a greater role in HPT (n=357) than in non-HPT (n=93) sib-pairs in determining most obesity measures. Similar to the mean values, these differences were most apparent in global and upper-body measures, with heritabilities ranging from 40% to 70% (P=0.05 to 0.0006) in HPT siblings and from 0% to 32% (P=NS) in non-HPT siblings. In summary, the present results suggest that HPT and non-HPT siblings drawn from the same families differ by the degree and distribution of body fat accumulation and that this difference is determined, at least in part, by genetic factors cosegregating with hypertension. This, in turn, suggests that a genetic link exists between obesity and hypertension in these families.

Canada↗

PubMed2001

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. Measurements included 24-hour blood pressure monitoring, fasting plasma lipids, insulin sensitivity determined with the Bergman minimal model, echocardiogram, microalbumin excretion, and inulin and lithium clearances. Compared with the white French Canadians, black patients had an attenuated nighttime reduction in blood pressure (P<0.02), increased cardiac dimensions (P<0.001), greater microalbumin excretion (P<0.05), increased inulin clearance (indicative of glomerular hyperfiltration; P<0.001), and decreased lithium clearance (indicative of increased sodium reabsorption in the proximal tubule; P<0.001). Blood pressure levels were not related to insulin resistance; although in blacks, the nighttime reduction in systolic blood pressure was inversely related to fasting plasma insulin (r=-0.18, P<0.04). In a stepwise multivariate analysis (including blood pressure levels and components of the insulin resistance syndrome as independent variables), race was the strongest predictor of left ventricular mass (r=0.53, P<0.000), relative wall thickness (r=0.49, P<0.000), and both inulin (r=0.53, P<0.000) and lithium (r=0.41, P<0.000) clearances. Nighttime systolic blood pressure was also a significant determinant of concentric left ventricular hypertrophy (r=0.37, P<0.000). In blacks, microalbumin excretion was related to insulin resistance. These observations are consistent with the hypothesis that there is a genetic contribution to cardiac hypertrophy, glomerular hyperfiltration, and sodium retention in blacks with essential hypertension.

Black People↗

PubMed2001

Ectopic and abnormal hormone receptors in adrenal Cushing's syndrome.

The mechanism by which cortisol is produced in adrenal Cushing's syndrome, when ACTH is suppressed, was previously unknown and was referred to as being "autonomous." More recently, several investigators have shown that some cortisol and other steroid-producing adrenal tumors or hyperplasias are under the control of ectopic (or aberrant, illicit, inappropriate) membrane hormone receptors. These include ectopic receptors for gastric inhibitory polypeptide (GIP), beta-adrenergic agonists, or LH/hCG; a similar outcome can result from altered activity of eutopic receptors, such as those for vasopressin (V1-AVPR), serotonin (5-HT4), or possibly leptin. The presence of aberrant receptors places adrenal cells under stimulation by a trophic factor not negatively regulated by glucocorticoids, leading to increased steroidogenesis and possibly to the proliferative phenotype. The molecular mechanisms responsible for the abnormal expression and function of membrane hormone receptors are still largely unknown. Identification of the presence of these illicit receptors can eventually lead to new pharmacological therapies as alternatives to adrenalectomy, now demonstrated by the long-term control of ectopic P-AR- and LH/hCGR-dependent Cushing's syndrome by propanolol and leuprolide acetate. Further studies will potentially identify a larger diversity of hormone receptors capable of coupling to G proteins, adenylyl cyclase, and steroidogenesis in functional adrenal tumors and probably in other endocrine and nonendocrine tumors.

Adrenal Gland Diseases↗

PubMed2001

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. Plasma ACTH was partially suppressed basally but increased after administration of ovine CRH. A 51-yr-old woman had ACTH-independent increases of plasma cortisol after 10 IU AVP im (292%), 100 microg GnRH iv (184%), or 10 mg cisapride orally (310%); cortisol also increased after administration of NaCl (3%), hCG, human LH, and metoclopramide. In a 61-yr-old man, cortisol was increased by AVP (349%), GnRH (155%), hCG (252%), and metoclopramide (191%). Another 53-yr-old male increased plasma cortisol after AVP (171%) and cisapride (142%). Cortisol secretion was also stimulated by vasopressin in a 54-yr-old female. This study demonstrates that subclinical secretion of cortisol can be regulated via the aberrant function of at least V1-vasopressin, LH/hCG, or 5-HT4 receptors in incidentally identified bilateral macronodular adrenal hyperplasia.

Adrenal Hyperplasia, Congenital↗

PubMed2001

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. OUTCOMES: The health outcomes 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 searches were conducted from the period of the last revision of the Canadian Recommendations for the Management of Hypertension (May 1998 to October 2000). Reference lists were scanned, experts were polled, and the personal files of the subgroup members and authors were used to identify other 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 lifestyle manoeuvres and 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 all aspects of the therapy of patients with hypertension, including lifestyle modifications proven to lower blood pressure, treatment thresholds, target blood pressures, choice of agents in various settings and strategies to enhance adherence. Lower thresholds for blood pressure treatment are advocated for people with other cardiovascular risk factors or established hypertensive target organ damage. Implicit in the recommendations for therapy is the principle that treatment should be individualized for each patient and the choice of agent should be dictated by coexistent conditions. For the treatment of uncomplicated essential hypertension, thiazides, beta-adrenergic antagonists, angiotensin-converting enzyme inhibitors or calcium channel blockers may be appropriate, depending on individual circumstances. VALIDATION: All recommendations were graded according to strength of the evidence and voted on by the Canadian Hypertension Recommendations Working Group. Only those recommendations achieving high levels of consensus are reported here. These guidelines will be updated annually.

Adult↗

PubMed2001

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. More recent in vivo studies have shown the prevention and regression of vascular lesions by apoptosis induction with medications (including AT1 receptor inhibitor).

Angiotensin II↗