Search PubMed⌕ Search

Biomedical subjects

P Hamet

Publications and source records attributed to P Hamet.

At least 163 records · Page 9Linked to original sources
PubMed1991

[Exposure to the risk of traffic accidents, a fundamental epidemiological parameter, and one difficult to measure].

This is a review of the literature dealing with exposure to the risk of traffic accidents. We present the principal definitions of this concept, the different measures of risk exposure, indicators of the risk of traffic accidents, and the advantages and disadvantages of the methods used for the collection of data. The validity of the measure of exposure to risk is analyzed as well. We conclude that while distance travelled is the principal measure of exposure to risk accepted by the research community, it is necessary to use a composite measure which also takes into account the risk associated with the driver.

Accidents, Traffic↗
PubMed1990

Atrial natriuretic factor constitutes an intrinsic functional unit within superior cervical ganglia of the rat.

The molecular forms of atrial natriuretic factor were studied in the sympathetic ganglia of the rat. The peptide atrial natriuretic factor was also tested for its ability to induce intracellular changes in ganglionic elements. Chromatographic evaluation of extracted ganglionic atrial natriuretic factor revealed the presence of proatrial natriuretic factor together with lower molecular weight peptides. Atrial natriuretic factor induced a maximal six-fold increase of cGMP accumulation within ganglia in vitro, most probably in principal ganglionic cells. Its effect on cGMP was not mediated by acetylcholine or any other neurotransmitter because it persisted after muscarinic receptor blockade and in a calcium-free medium and was not affected by ganglia decentralization. Thus, atrial natriuretic factor appears to be produced by a structural neural component of ganglia (in preganglionic cholinergic neurons or small intensely fluorescent cells?) and has receptors at sites different from its source. It is suggested that atrial natriuretic factor may be locally involved in the process of neurotransmission and may be yet another peptide neurotransmitter and/or neuromodulator.

Animals↗
PubMed1990

Characterization of a primate model of hypertension. The response of hypertensive and normotensive male vervets (Cercopithecus aethiops) to cold pressor stress, captopril administration, and acute bolus of atrial natriuretic factor.

In feral populations of African green monkeys or vervets (Cercopithecus aethiops), between 5 and 15% of adults have spontaneously elevated blood pressure (BP). We report here the initial biological and pharmacological characterization of this potential animal model of hypertension. Captive male monkeys with elevated systolic pressures show a modest pressure increase in response to stressors such as capture, phlebotomy and cold challenge. Acute captopril administration lowers BP in monkeys with high blood pressure (HBP), but has no effect on BP in control animals. Furosemide does not acutely reduce BP. Animals with elevated BPs have lower levels of angiotensin II than do age- and weight-matched controls. An acute infusion of atrial natriuretic factor (ANF) diminishes BP and stimulates urinary output in control and HBP vervets. However, both effects are more pronounced in animals with HBP. Heart rate is not affected by any of the experimental manipulations. Taken together, these data suggest that African green monkeys with spontaneously elevated BP may be a useful experimental model for particular types of human hypertension. Additional studies are required to complete the endocrine and pharmacological characterization of individual animals with HBP.

Analysis of Variance↗
PubMed1990

Decrease of blood pressure in spontaneously hypertensive mice by heat treatment.

Although the increased sensitivity of hypertensive animals to heat stress has been reported, the effect of chronic heat exposure has not been examined. The specific goal of the present investigation was to study the impact of chronic heat treatment on the blood pressure of spontaneously hypertensive mice. Chronic 40 degrees C heat exposure for 5 min daily progressively lowered basal blood pressure in hypertensive mice within 20 days, without any change in normal mice. In fact, after 35 days of chronic heat treatment, the basal blood pressure of hypertensive mice was indistinguishable from that of the normotensives. Repeated immobilization and prewarming as normal procedures for recording blood pressure contributed to the decrease in blood pressure by 10 to 12 mm Hg, but chronic heat by itself was significantly more potent in reducing it by an additional 20 mm Hg. After the discontinuation of chronic heat application, the basal blood pressure of hypertensive mice returned with time to the level registered in sham-handled hypertensive controls. These results demonstrate that, although acute heat is more detrimental to hypertensive mice, brief, chronic exposure to mild heat stress is beneficial in that it normalizes basal blood pressure.

Animals↗
PubMed1990

Increase of calmodulin activator in hypertension. Modulation by dietary sodium and calcium.

The aim of this study was to investigate the effects of dietary calcium and sodium on blood pressure (BP) in normotensive rats (Wistar, WKY), spontaneously hypertensive rats (SHR) and Dahl rats and on calmodulin (CaM) activator, a newly-discovered hydrophobic compound that increases CaM activity in SHR and spontaneously hypertensive mice (SHM) tissues (J Clin Invest 82:276, 1988). The CaM activator was assessed by its capacity to stimulate a CaM-dependent phosphodiesterase (CaM-PDE). In Wistar rats, which were fed a high sodium diet (3.5%), BP significantly increased (P less than .01) from 106 +/- 4 to 128 +/- 8 mm Hg in parallel to an elevation of the CaM activator from 1.57 +/- 0.14 to 2.80 +/- 0.18 U. WKY, SHR, and Dahl salt-sensitive (DS/JR) and salt-resistant (DR/JR) rats were given low (0.15%) or high (2.5%) Ca diets, both with 1% sodium. In rats receiving high dietary Ca the progression of hypertension diminished and BP was lower in SHR (156 +/- 4 mm Hg) and young DS/JR rats (125 +/- 3 mm Hg) than in those receiving low dietary Ca (192 +/- 10 and 183 +/- 2 mm Hg). There was a concomitant decrease of CaM activator in these animals to levels indistinguishable from those of WKY or DR/JR rats. The activator was also found in the heart, kidneys and erythrocytes from SHM. In the presence of exogenously added CaM, lipidic extracts from the SHM heart showed augmented CaM-PDE activity relative to normotensive preparations. This difference was eliminated by trifluoperazine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Increased inositol trisphosphate in erythrocytes of spontaneously hypertensive rats.

Phosphoinositide (PI) turnover, a major control mechanism of cellular function, was studied in erythrocytes of spontaneously hypertensive rats (SHR). After 32p (inorganic phosphate) incorporation in intact cells, release of inositol trisphosphate (IP3) and inositol bisphosphate (IP2) from membrane fractions was measured in SHR with or without prior Ca2+ stimulation. The present study revealed an increase of Ca2(+)-stimulated IP3 release in SHR, suggesting high polyphosphoinositide phosphodiesterase activity in this model of hypertension.

Animals↗
PubMed1990

Atrial natriuretic peptide--cyclic GMP coupling and urinary sodium excretion during acute volume expansion in man.

The present study examines hormonal and renal responses to acute volume expansion in normal man, with particular emphasis on the atrial natriuretic peptide (ANP)--cyclic GMP coupling. Two liters of isotonic saline were infused into eight normotensive male subjects over a 1-h period. Plasma and urinary measurements were made before, during, and up to 300 min after the start of the saline infusion. With the initial increase in urinary sodium excretion there were increases in plasma ANP and plasma cyclic GMP, which reached maximum levels at 15 min after the end of the saline infusion. Urinary cyclic GMP increased gradually during saline infusion up to approximately 60 min after the end of the infusion. Plasma ANP and plasma and urinary cyclic GMP excretion gradually declined thereafter. By contrast, urinary sodium excretion remained elevated up to the end of the observation period. The saline infusion was associated with marked reductions in plasma renin activity and aldosterone, which persisted up to the end of the study. These results suggest a coupling between the increases in plasma ANP, the production of cyclic GMP, and urinary sodium excretion, in particular during the initial renal response to acute volume expansion. However, other mechanisms including the suppression of the renin--angiotensin--aldosterone system may become increasingly important in the later natriuretic response to acute volume expansion.

Adult↗
PubMed1990

Increased transcription of a major stress gene in spontaneously hypertensive mice.

Environmental stress factors, including temperature, modify the severity of hypertension, a genetic disease. Hypertensive animals and humans respond abnormally to heat exposure, and this abnormality is reflected at the cellular level by an increment in a major stress (heat-shock) gene expression. The present studies demonstrate that increased hsp70 gene expression is due to its heightened transcription rate. The genetic basis of environmental susceptibility to hypertension may thus involve an abnormal control of heat shock genes.

Amanitins↗
PubMed1990

Effect of prolonged high salt diet on atrial natriuretic factor in rats.

Normotensive Sprague-Dawley rats were given 8% NaCl for 5 weeks. This salt load did not affect their blood pressure nor hematocrit, and plasma atrial natriuretic factor (ANF) showed no change at 3 weeks but decreased after 5 weeks of the experimental period when compared with control rats. The responsiveness of particulate guanylate cyclase and formation of cGMP in ANF target organs suggested an augmented baseline activity of the cGMP system but its relative hyporesponsiveness to exogenous ANF following prolonged salt loading. Decreased plasma ANF levels cannot be explained by its altered production since atrial levels of the peptide were comparable in rats with or without salt loading. Atrial ANF mRNA was unaffected by the salt regimen. This study demonstrates that plasma ANF does not increase during long-term NaCl loading and even decreases after 5 weeks of 8% NaCl. The changes in plasma ANF are associated with changes in the functional state of ANF receptors coupled to particulate guanylate cyclase, but in the opposite direction than expected from lowered plasma ANF. Thus, ANF may not play a significant role in the regulation of sodium excretion in response to prolonged high salt consumption or, if it does, it is not reflected by expected changes in its plasma levels.

Adrenal Cortex↗
PubMed1990

[Intrinsic and extrinsic factors implicated in cell proliferation of vascular smooth muscle in hypertension and diabetes].

The increased potential for growth of vascular smooth muscle cells in one of the key abnormalities in the development of essential hypertension, diabetic microangiopathy and atherosclerosis. The underlying mechanisms seem to be extrinsic (increased platelet-derived growth factor-like activity) and intrinsic (increased rate of growth, greater maximal response to growth factors and less contact inhibition). In this article, the authors discuss the primary role of an alteration in vascular smooth muscle cellular proliferation in hypertension, the extrinsic growth factors contained in platelet extracts of diabetic and hypertensive subjects and the specific effects of insulin and antihypertensive therapy on this pro-mitotic platelet activity. The result of experimental studies in our laboratory and in other studies suggest that genetic factors and therapeutic intervention could control the growth of vascular smooth muscle cells and that further evaluation of anti-hypertensive therapy may be necessary.

Animals↗
PubMed1990

Single-channel analysis of the electrical response of bovine aortic endothelial cells to bradykinin stimulation: contribution of a Ca2(+)-dependent K+ channel.

The contribution of Ca2(+)-dependent K+ [K(Ca2+)] channels to the electrical response of cultured bovine aortic endothelial cells following bradykinin stimulation was investigated using the patch-clamp method in the cell-attached configuration. Results indicate (1) that bradykinin activates a voltage-insensitive K(Ca2+) channel of 40 pS in 150 mmol/l KCl through a second messenger mechanism; (2) that the time-course of the K(Ca2+) channel activation process corresponds to the time-dependent changes in cytosolic Ca2+ triggered by bradykinin; and (3) that there is a direct correlation between the cellular hyperpolarization induced by bradykinin and the activation of the K(Ca2+) channels. It is proposed that the hyperpolarization of bovine aortic endothelial cells following bradykinin stimulation is a result of the activation of K(Ca2+) channels, and not of a modification in the gating behaviour of an inward rectifying K+ channel (lk1) that is also observed in these cells. A more negative membrane potential may, in turn, enhance the Ca2+ influx involved in the bradykinin-induced Ca2+ signalling process.

Animals↗
PubMed1990

Heat stress genes in hypertension.

Genetically hypertensive animals such as spontaneously hypertensive rats (SHR) and mice are more sensitive to thermal stress than normotensive controls. Genetic breeding experiments have demonstrated that the gene responsible for thermosensitivity segregates with an increase in blood pressure in the F2 generation and represents a genetic locus of hypertension. Due to a higher transcription rate of the heat shock protein 70 (hsp70) gene, which is a major heat stress gene, the accumulation of hsp messenger (m)RNA is increased in hypertension. Higher thermosensitivity and increased hsp mRNA accumulation are also observed in neonatal cardiomyocytes and cultured vascular smooth muscle cells from SHR, suggesting that these abnormalities are primary in character. This higher hsp70 transcription rate in hypertension could be due to an abnormality in the promoter region, to an interaction between heat stress trans-acting factor and heat stress element within the promoter of hsp70 or to an abnormal activation of heat stress trans-acting factor. A study using recombinant inbred animals has indicated that RT1 complex gene(s), a major histocompatibility complex in the rat, may be involved in the development of hypertension. These findings, together with the fact that hsp70 is located in the major histocompatibility complex, suggest that hsp70 gene or associated genes within the RT1 complex are responsible for environmental control of the expression of hypertension.

Animals↗
PubMed1989

Atrial natriuretic factor-induced egression of cyclic guanosine 3':5'-monophosphate in cultured vascular smooth muscle and endothelial cells.

The induction of cyclic GMP formation in target tissues, i.e. vascular smooth muscle and endothelial cells, by atrial natriuretic factor is followed by its egression into plasma and urine. Since the extracellular appearance of this cyclic nucleotide is used as a marker of atrial natriuretic factor's biological activity, the present study was designed to investigate the characteristics of its egression to the extracellular fluid. In contrast to cyclic AMP, whose profile of egression in time closely follows its intracellular levels, cyclic GMP egression begins with the intracellular decline but continues for a prolonged period, even accumulating for up to 24 h in the extracellular medium. The relative egression of cyclic GMP decreases slightly in the presence of phosphodiesterase inhibitors. On the other hand, the process is sensitive to temperature, inhibited by such agents as probenecid, and occurs against a gradient of 7 orders of magnitude. Large increases of cyclic AMP, as induced by forskolin, can effectively compete for the cyclic GMP transport system, resulting in a 3-fold rise in intracellular cyclic GMP levels, which corresponds to a 3-fold decline of extracellular accumulation. Although the biological significance of cyclic GMP egression is unknown, the results of this study suggest that the process may be one of the significant contributors to the control of cyclic GMP levels in the cell with potential physiological consequences.

Animals↗
PubMed1989

Release of atrial natriuretic factor (ANF) induced by acute airway obstruction.

The aim of this study was to measure the effects of an increase in negative intrathoracic pressure on the release of ANF. With the subjects seated comfortably, 3 control blood samples were obtained over 30 minutes. Eight subjects then breathed for 30 min. through an inspiratory resistance in such a way that maximal inspiratory pleural pressures were between -30 to -40 cmH2O. Three blood samples were withdrawn after 20, 25, and 30 min., with the subject still breathing against the artificial resistance. Plasma concentrations of ANF were analysed by RIA. They measured: control value 24.6 +/- 3.7 pg ANF/mL (X +/- SE); with resistance 37.1 +/- 8.1 pg/mL (p less than or equal to .05). These results suggest that ANF could be released during an asthma attack.

Adult↗
PubMed1989

Effect of prolonged infusion of ANF in normotensive and hypertensive monkeys.

It is now recognized that bolus and short-term infusions of atrial natriuretic factor (ANF) into different species lead to a slight and transient decrease of blood pressure, while prolonged infusions cause a significant blood pressure reduction in hypertensive but not in normotensive rats. The present study was designed to evaluate the effects of prolonged ANF infusions on blood pressure and humoral parameters in normotensive and hypertensive African green monkeys (Cercopithecus aethiops). Human-ANF infusions (100 ng/kg.hr) in conscious, normotensive vervets for a period of 48 hours evoked highly significant decreases of blood pressure (from 124/65 to 104/53 mm Hg), plasma renin activity, aldosterone, and hematocrit. This fall in blood pressure was not accompanied by an increase of plasma cGMP levels at the end of the infusion. Forty-eight hours after the infusion was terminated, the decrease in blood pressure was still significant (97/46 mm Hg), as was the drop in aldosterone. In hypertensive monkeys, systolic blood pressure declined from 175 +/- 8 to 130 +/- 8 mm Hg, while diastolic pressure fell from 117 +/- 10 to 88 +/- 4 mm Hg. These data demonstrate that the chronic infusion of ANF in both normotensive and hypertensive vervets has more profound effects than does acute bolus administration, effects that persist for a prolonged period of time after discontinuation of the infusion.

Animals↗
PubMed1989

Biochemical mechanisms of atrial natriuretic factor action.

Since atrial natriuretic factor (ANF) is a natriuretic and vasodilatory hormone, its mechanisms of action expectedly involve so-called negative pathways of cell stimulation, notably cyclic nucleotides. Indeed, the guanylate cyclase-cyclic GMP (cGMP) system appears to be the principal mediator of ANF's action. Specifically, particulate guanylate cyclase, a membrane glycoprotein, transmits ANF's effects, as opposed to the activation of soluble guanylate cyclase such agents as sodium nitroprusside. The stimulation of particulate guanylate cyclase by ANF manifests several characteristics. One of them is the functional irreversibility of stimulation with its apparent physiological consequences: the extended impact of ANF on diuresis and vasodilation in vivo lasts beyond the duration of increased plasma ANF levels and is accompanied by a prolonged elevation of cGMP. Another characteristic is the parallelism between guanylate cyclase stimulation and increases of cGMP in extracellular fluids. cGMP egression appears to be an active process, yet its physiological implications remain to be uncovered. In heart failure, cGMP continues to reflect augmented ANF levels, suggesting that in this disease, the lack of an ANF effect on sodium excretion is due to a defect distal to cGMP generation. In hypertension, where ANF levels are either normal or slightly elevated, probably secondary to high blood pressure, the ANF responsiveness of the particulate guanylate cyclase-cGMP system, the hypotensive effects, diuresis and natriuresis are exaggerated. The implications of this exaggerated responsiveness of the ANF-cGMP system in the pathophysiology of hypertension and its potential therapeutic connotations remain to be evaluated.

Animals↗
PubMed1989

Cardiac and vascular effects of atrial natriuretic factor and sodium nitroprusside in healthy men.

To assess the contribution of venous effects to the hemodynamic changes caused by atrial natriuretic factor (ANF), the cardiac and peripheral effects of ANF were compared with those induced by the venoarterial vasodilator sodium nitroprusside. On 3 different days, eight healthy subjects received 2-hour infusions of either ANF, sodium nitroprusside, or placebo, by a single-blind crossover design. ANF was administered at a rate of 15 ng/kg/min for hour 1 and 50 ng/kg/min for hour 2; each infusion rate was preceded by a 50-micrograms bolus. The lower ANF infusion rate increased plasma cGMP fourfold, but only modest cardiovascular effects (small decreases in left ventricular end-diastolic and end-systolic volumes) were noted. At the higher ANF infusion rate, left ventricular volumes and intravascular volume, as indirectly assessed by changes in hematocrit levels, decreased further, which resulted in decreases in stroke volume, cardiac index, and systolic blood pressure. No evidence for arterial vasodilation (no decrease in diastolic blood pressure, total peripheral resistance, or forearm resistance) was obtained, and no increase in sympathetic activity was noted. In contrast, sodium nitroprusside caused arterial vasodilation, an increase in cardiac index, and significant increases in sympathetic activity. We conclude that short-term increases in plasma ANF within the physiologic range primarily affect the venous vascular bed (by decreasing intravascular volume or by venodilation) without increasing sympathetic activity.

Adult↗