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Biomedical subjects

P Hamet

Publications and source records attributed to P Hamet.

At least 19 recordsLinked to original sources
PubMed1992

Prevalence, control and awareness of high blood pressure among Canadian adults. Canadian Heart Health Surveys Research Group.

OBJECTIVE: To estimate the prevalence and distribution of elevated blood pressure (BP) among Canadian adults and to determine the level of control, treatment, awareness and prevalence of other risk factors among adults with high BP. DESIGN: Population-based cross-sectional surveys. SETTING: Nine Canadian provinces, from 1986 to 1990. PARTICIPANTS: A probability sample of 26,293 men and women aged 18 to 74 years was selected from the health insurance registers in each province. For 20,582 subjects, BP was measured at least twice. Nurses administered a standard questionnaire and recorded two BP measurements using a standardized technique. Two further BP readings, anthropometric measurements and a blood specimen for lipid analysis were obtained from those subjects who attended a clinic. OUTCOME MEASURES: Mean values of systolic and diastolic BP, prevalence of elevated BP using different criteria, and prevalence of smoking, elevated blood cholesterol, body mass index, physical activity and presence of diabetes by high BP status are reported. MAIN RESULTS: Sixteen percent of men and 13% of women had diastolic BP of 90 mm Hg or greater or were on treatment (or both). About 26% of these subjects were unaware of their hypertension, 42% were being treated and their condition controlled, 16% were treated and not controlled, and 16% were neither treated nor controlled. Use of non-pharmacologic treatment of high BP with or without medication was low (22%). Hypertensive subjects showed a higher prevalence of elevated total cholesterol, high body mass index, diabetes and sedentary lifestyle than normotensive subjects. Most people with elevated BP were in the 90 to 95 mm Hg range for diastolic pressure and 140 to 160 mm Hg range for systolic pressure. Prevalence of high isolated systolic BP sharply increased in men (40%) and women (49%) 65 to 74 years old. CONCLUSIONS: The relatively low level of control of elevated BP calls for population and individual strategies, stressing a non-pharmacologic approach and addressing isolated systolic hypertension in the elderly.

Adult↗
PubMed1992

In vivo measurement of atrial natriuretic peptide receptors using nuclear imaging.

We have successfully visualized atrial natriuretic peptide (ANP) receptors in vivo using nuclear imaging. 123I-Labelled ANP, injected in green vervet monkeys, was rapidly bound to ANP receptors in the kidneys and lungs. That the observed uptake was receptor mediated was demonstrated with competition studies using simultaneous injection of unlabelled ANP 99-126. It was possible to distinguish between the ANP receptor subtypes by the use of selective antagonists. Thus coinjection of ANP 102-121-des[Gln, Ser, Gly, Leu, Gly] (C-ANP), an ANP analog that selectively binds to the ANP C-receptor, decreased uptake in the kidneys by 50% but increased relative uptake in the lungs and soft tissues. This method permits for the first time, the dynamic in vivo analysis of ANP receptors and their interaction with endogenous ligand. Differences and changes in local ANP receptor concentrations and occupancy could be detected. Since ANP receptor density and affinity are influenced by various physiological and pathological conditions, clinical and diagnostic applications seem possible.

Animals↗
PubMed1992

Epidemiological evidence of an interaction between calcium and sodium intake impacting on blood pressure. A Montréal study.

Nutritional calcium and sodium are considered to be important regulators of blood pressure. This study was performed on 182 randomly selected Canadians from Montréal to test the relative contribution of these ions to systolic and diastolic blood pressure, as well as their interaction with other demographic indices. Multiple analysis of the total study population revealed that 28% (P less than .001) of systolic blood pressure was predicted by gender sodium, and calcium interaction (P = .003), weight, and the additive effect of age and weight. The same characteristics contributed to 37% (P less than .001) of diastolic blood pressure with an additional contribution of alcohol intake. Analysis by terciles of sodium and calcium intake indicated that the positive effect of sodium on blood pressure occurred only in subjects given a low calcium diet, whereas blood pressure was lowest in the tercile of both high calcium and sodium intake. The impact of the sodium and calcium interaction on blood pressure represented as much as a 10 mm Hg decrement of systolic blood pressure with 400 mg calcium/1000 kcal intake at the highest level of sodium consumption and a 6 mm Hg decrease for diastolic blood pressure. In subjects without a family history of hypertension, the same indices contributed up to 53% of systolic and 55% of diastolic blood pressure with a synergetic effect of sodium and calcium, indicating that blood pressure was lowest in subjects given a high calcium and sodium diet. For subjects with a family history of hypertension, there was no significant impact of sodium, whereas calcium intake contributed negatively to both systolic and diastolic blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Expression of hsp70 gene in lymphocytes from normotensive and hypertensive humans.

The impact of environmental factors on hypertension depends to a certain extent on the individual's genetic background. Environmental temperature is one of the known modulators of blood pressure. We have previously demonstrated abnormal expression of a major environmentally-controlled gene, hsp70, in hypertensive mice and rats. We have developed a simple ex vivo method for the evaluation of hsp genes expression in humans. In the present study, we investigated the accumulation of hsp70 mRNA in lymphocytes from normotensive and hypertensive humans. The data showed a higher accumulation of hsp70 mRNA in lymphocytes from hypertensives vs normotensives (2.04 +/- 0.35 vs 1.48 +/- 0.29 OD mm2, P < 0.05) submitted to heat stress (15 min at 42 degrees C). Basal levels were the same in both groups (0.11 +/- 0.01 vs 0.10 +/- 0.01 OD mm2, respectively). These results support our hypothesis that alterations in the expression of a major environmentally-controlled gene, hsp70, may be involved in enhanced environmental responses even in human hypertension.

Female↗
PubMed1992

Accelerated entry of aortic smooth muscle cells from spontaneously hypertensive rats into the S phase of the cell cycle.

The present study was designed to characterize the growth kinetics of the exaggerated proliferative response to mitogens of vascular smooth muscle cells from spontaneously hypertensive rats compared with cells from normotensive Wistar-Kyoto controls. Cellular DNA content, analyzed by flow cytometry, demonstrated a 4-h accelerated entry into the S phase of the cell cycle of vascular smooth muscle cells from spontaneously hypertensive rats; the significant (4.5-fold) increase in the percentage of cells in the S phase occurred between 8 and 12 h after calf serum stimulation. A 3.9-fold increase of cells in the S phase was seen in the normotensive controls only between 12 and 16 h. Transit through the cell cycle was quantitated by flow cytometry using the Hoechst 33,342--bromodeoxyuridine substitution technique. Vascular smooth muscle cells from spontaneously hypertensive rats went through the cell cycle 4 h ahead of cells from normotensive Wistar-Kyoto rats. This accelerated transit of spontaneously hypertensive rat cells was mostly due to an earlier entry into the S phase. Persistence of this new intermediate phenotype in cell culture suggests its primary pathogenetic role in spontaneous hypertension.

Animals↗
PubMed1992

Enhanced growth-dependent expression of TGF beta 1 and hsp70 genes in aortic smooth muscle cells from spontaneously hypertensive rats.

Enhanced proliferation of vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) as compared with Wistar-Kyoto rats (WKY) persists in long-term culture and is characterized by an accelerated entry of these cells into the synthetic S phase of the cell cycle and a higher specific growth rate, particularly evident at high cell density. In the present study, we investigated by Northern blot experiments the expression of genes putatively involved in the regulation of VSMC growth. One of them is the transforming growth factor beta 1 gene (TGF beta 1), a bifunctional modulator of cell growth whose action is dependent on cell density. The accumulation of TGF beta 1 mRNA was enhanced in growing SHR cells at every density studied as early as 24 h after inoculation with a further increase at later times. Protooncogenes c-fos and c-myc, which have been implicated in G1/S phase transition, have also been investigated in VSMC by Northern blot analysis. At low cell density, calf serum stimulated c-fos and c-myc mRNA expression was comparable in WKY and SHR cells whereas at high cell density, c-fos induction was higher in VSMC from SHR. SHR VSMC respond more to mitogenic stimulation and to environmental (e.g., heat) stress, particularly when growing near saturation density. hsp70 constitutes a gene family responsive to environmental stimuli (heat) and to mitogenic stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Restriction fragment length polymorphism of hsp70 gene, localized in the RT1 complex, is associated with hypertension in spontaneously hypertensive rats.

Previous studies from our laboratory have demonstrated that the intermediate phenotype of thermosensitivity is present in hypertensive mice and rats. Increased expression of hsp70 caused by increased transcription rate was demonstrated in vivo, in organs, and in cultured cells from spontaneously hypertensive rats and hypertensive mice. In this study, a polymorphism of this gene was revealed with BamHI enzyme by using a human hsp70 probe. A 4.4-kb fragment was visualized in normotensive rats (Brown-Norway BN.lx and Sprague-Dawley), and a 3.0-kb fragment was found in spontaneously hypertensive rats (SHR) of three different origins and in Wistar and Buffalo rats. Both fragments were present in the Wistar-Kyoto rat strain. The present study mapped the polymorphism of hsp70 into the RT1 complex in BN.1K and SHR.1N congenic strains. The hsp70 restriction fragment length polymorphism is associated with a blood pressure difference of 15 mm Hg in recombinant inbred strains. These results justify the search for a mechanism by which hsp70 could influence blood pressure.

Animals↗
PubMed1992

Abnormal hsp70 gene expression: its potential key role in metabolic defects in hypertension.

1. Abnormal heat stress gene hsp70 expression has been demonstrated in organs as well as in cultured cells from spontaneously hypertensive rats and mice. 2. The polymorphism of hsp70, which is localized in the major histocompatibility complex, appears to segregate with a significant portion of hypertension. 3. Abnormal hsp70 expression may lead to anomalies in its feedback regulation, particularly since the steady state level of heat stress protein HSP70 seems to be lower in hypertensive than in normal animals. 4. Another biological consequence could be a modification of the effectiveness of cortisol, which may be involved in metabolic components of the pathogenesis of hypertension.

Animals↗
PubMed1991

Follow-up of cyclosporin A treatment in type 1 (insulin-dependent) diabetes mellitus: lack of long-term effects.

In the Canadian/European randomized controlled study on cyclosporin A (CsA) in recent onset Type 1 (insulin-dependent) diabetes, treatment with the immunosuppressive drug had increased and maintained Beta-cell function and clinical remission during the first 12 months. Following discontinuation of the study drug and double-blinding after a mean of 13.8 months former CsA patients doubled the daily insulin dose within 6 months reaching the level of former placebo patients. The difference in Beta-cell function between the two groups was also lost. Metabolic control (HbA1c) was transiently worse in the former CsA group. Adverse effects of cyclosporin A on systolic blood pressure, haemoglobin levels, serum potassium and creatinine levels also remitted during that time. We conclude that treatment with cyclosporin A for a mean of 13.8 months had no long-lasting effect on the course of Type 1 diabetes persisting beyond drug discontinuation.

Adolescent↗
PubMed1991

Vascular smooth muscle cell proliferation and its therapeutic modulation in hypertension.

The increased growth potential of vascular smooth muscle cells (VSMCs) represents one of the crucial anomalies responsible for the development of essential hypertension, diabetic macroangiopathy, and atherosclerosis. The exaggerated response to growth factors of VSMC from spontaneously hypertensive rats (SHRs) persists in culture when compared with normotensive Wistar-Kyoto control rats, indicating an intrinsic defect in the hypertension-producing mechanism. This greater proliferation is characterized by two intermediate phenotypes: (1) accelerated entry into the S phase of the cell cycle, which results from hyperresponsiveness to epidermal growth factor and platelet-derived growth factor, and (2) abnormal contact inhibition. The enhanced expression of transforming growth factor beta 1 (TGF-beta 1) messenger ribonucleic acid in SHRs precedes this altered contact inhibition, and only VSMCs from SHRs respond to exogenously added TGF-beta 1 at a high cell density, which suggests that abnormal TGF-beta 1 autoregulation may be implicated in the second phenotype. Platelets contain major growth factors for VSMC. Platelet extracts from hypertensive and diabetic patients present augmented growth-promoting activity on VSMCs, which is most evident when both diseases occur simultaneously. Growth-promoting activity may be further influenced by antihypertensive therapy. This growth-promoting activity is increased by hydrochlorothiazide but not by indapamide, atenolol, or captopril in diabetic hypertensive and nondiabetic hypertensive patients. In conclusion, VSMCs in hypertension manifest an intrinsic growth defect that is modulated by extrinsic platelet growth factors and antihypertensive drugs.

Animals↗
PubMed1991

The effect of Diamicron on the secretion and action of insulin.

We studied, in healthy subjects (n = 4) and in non-insulin-dependent diabetics (n = 4), the effect of a new sulfonylurea, Diamicron, on the secretion and action of insulin, using a mathematical model. This model analyzed, during an intravenous glucose tolerance test, the response of the first and second phase of insulin secretion in relation to the variations in blood glucose (insulin secretion) and the rate of decline in the blood glucose curve in relation to the variations in insulin (insulin response). Each subject was studied twice: once after administration of placebo and once after administration of Diamicron 80 mg 90 min after intravenous injection of 300 mg/kg of D-glucose. In healthy subjects, the glucose load after placebo induced an insulin response of 7.4 +/- 1.0 and 11.3 +/- 1.4 microU ml-1 min-1 mg-1 dl-1 for the first and second phases, respectively, and an insulin sensitivity evaluated to be 4.7 +/- 0.3 min microU-1 ml-1. Following the administration of Diamicron, the insulin response to the same glucose load increased two-fold and five-fold for the first and second phases, respectively, and the insulin sensitivity also increased by a factor of 2. In diabetic subjects the insulin response to the glucose load after placebo was markedly decreased (2.2 +/- 0.5 and 2.5 +/- 0.3 microU ml-1 min-1 mg-1 dl-1, respectively) as was the insulin sensitivity (2.5 +/- 0.3 min microU-1 ml-1). The administration of Diamicron increased all these parameters by a factor of 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗
PubMed1991

Milk- and soy-protein ingestion: acute effect on serum uric acid concentration.

Acute effect of the ingestion of 80 g each of casein, lactalbumin, and soybean isolate on serum and urinary uric acid concentrations was investigated in 10 healthy subjects. Serum and urinary uric acid concentrations were measured before and after the ingestion of proteins. Serum uric acid decreased significantly 3 h after ingestion of lactalbumin and casein but increased after soybean consumption. Urate clearance was significantly increased after ingestion of each of the three proteins. Multivariate analysis of urate clearance during lactalbumin and casein loads showed that independent correlation was obtained for serum alanine and urea concentration. These results demonstrate that, in addition to their known uricosuric effect, milk proteins acutely decrease serum uric acid concentration. Analysis of the effects of lactalbumin and casein on urinary uric acid elimination suggests that the uricosuric effect of proteins is a multifactorial phenomenon.

Adult↗
PubMed1991

Influence of environmental temperature on the blood pressure of hypertensive patients in Montréal.

To assess the influence of environmental temperature on blood pressure, we analyzed 42,813 readings of systolic and diastolic blood pressures in recumbent and upright positions in 2,000 hypertensive patients in our clinic in correlation to noon temperature and mean daily temperature in Montréal. The sample comprised 860 men and 1140 women with an average age of 55 years. Analysis of variance showed highly statistically significant negative correlations for all blood pressure values between different noon temperature, as well as mean daily temperature, groups. The greatest difference for systolic blood pressure was 7 mm Hg, and for diastolic blood pressure it was 3 mm Hg, within the -24 degrees C to 27 degrees C temperature range. The same relationship between blood pressure and different environmental temperatures was also seen when the blood pressure recordings were divided between temperature below 0 degree C and above 0 degree C, ie, within the winter or summer months. This environmental effect may have a clinically significant impact because thermosensitivity appears to be related to hypertension.

Adult↗
PubMed1991

Distinct plasma atrial natriuretic factor, renin and aldosterone responses to prolonged high-salt intake in hypertensive and normotensive rats.

Five weeks of high (8%) sodium intake, resulting in a decline of plasma atrial natriuretic factor (ANF) in normotensive Wistar-Kyoto (WKY) and Wistar rats, did not affect plasma ANF in spontaneously hypertensive rats (SHR) which became severely hypertensive. Regardless of salt consumption, SHR presented more pronounced glomerular particulate guanylate cyclase activation after large ANF doses in vitro than normotensive rats. In response to salt loading, plasma renin activity (PRA) and plasma aldosterone unexpectedly increased in SHR, in contrast to their decrease in the normotensive strains. Thus, SHR fail to react to prolonged high-salt intake as do normotensive rats, i.e. by a fall in plasma ANF, PRA and plasma aldosterone, and have higher stimulated glomerular particulate guanylate cyclase activity. Thus, ANF and its target response in SHR, as well as the PRA-plasma aldosterone reaction to prolonged salt loading, are distinct from those in normotensive strains. Since the relatively increased ANF and its target action in SHR appear to be a reactive antihypertensive defense rather than a primary event, systems other than ANF probably play an important role in the high salt-induced accelerated hypertension of SHR.

Aldosterone↗
PubMed1991

Cell biology of atrial natriuretic peptide.

Atrial natriuretic peptide (ANP) exhibits a wide spectrum of cardiovascular, endocrine, metabolic and renal actions. cGMP is the major mediator of ANP at the cellular level and only tissues possessing particulate guanylate cyclase appear to present ANP-induced actions. Three types of ANP receptors have recently been cloned. Two of them (A and B receptors) are homologous and contain guanylate cyclase catalytic domains. The C receptor could possibly regulate the metabolic fate of ANP. Data obtained by the radiation inactivation method suggest the presence of an inter- or intramolecular inhibitory component of nearly 90 kilodaltons that represses the catalytic activity of guanylate cyclase within its membrane environment. The mechanism of guanylate cyclase stimulation by ANP could involve this inhibitory component. Preliminary data suggest that the hyperresponsiveness of the particulate guanylate cyclase/cGMP system in hypertension occurs through modulation of the inhibitory component.

Animals↗
PubMed1991

Interactions among calcium, sodium, and alcohol intake as determinants of blood pressure.

It has been reported that calcium intake may effectively modulate the expression of hypertension affected by sodium. The present study extends our previous analysis of this calcium-sodium interaction, additionally demonstrating that calcium, sodium, and alcohol intake further contribute to both systolic and diastolic blood pressures in normotensive subjects. Calcium intake was related to lower blood pressure over all ranges of sodium and alcohol intake, and alcohol intake contributed positively and significantly to both systolic and diastolic blood pressures. However, sodium was associated with increased blood pressure only at low calcium intake, particularly in subjects who consumed large amounts of alcohol. This study points to a significant interaction among sodium, calcium, and alcohol intake as determinants of blood pressure, which, together with gender and weight, contribute to 31% of systolic blood pressure and with the addition of age to 36% of the variance in diastolic blood pressure.

Adult↗