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Biomedical subjects

S Laurent

Publications and source records attributed to S Laurent.

At least 235 records · Page 13Linked to original sources
PubMed1987

Opposite central cardiovascular effects of nifedipine and BAY k 8644 in anesthetized rats.

The central cardiovascular effects of the calcium channel inhibitor (CCI) nifedipine and the calcium channel activator BAY k 8644 (BAY) were studied in pentobarbital-anesthetized and ventilated normotensive Wistar-Kyoto (WKY) or spontaneously hypertensive rats (SHR). Both drugs were administered under a 1.5 microliter volume into the lateral ventricle of the brain (intracerebroventricular, i.c.v.). The injection of vehicle (ethanol) alone did not significantly change mean arterial pressure (MAP) or heart rate (HR). Nifedipine (5 and 50 micrograms/kg) and BAY (5 and 50 micrograms/kg) induced opposite effects on MAP when centrally injected. Nifedipine decreased MAP and HR while BAY increased MAP without significant change in HR. These effects are likely to be of central origin, because they were suppressed by ganglionic blockade with hexamethonium and by reserpine. Previously i.c.v. administered nifedipine (5 micrograms/kg) antagonized pressor response to BAY (5 micrograms/kg i.c.v.). Changes in MAP and HR were significantly more marked in SHR than in WKY. These results indicate that a calcium channel inhibitor and a calcium channel activator can modulate in opposite fashion central mechanisms involved in blood pressure control.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1987

Cardiac hypertrophy and aortic distensibility in essential hypertension.

Reduced aortic distensibility and compliance may participate in the genesis of cardiac hypertrophy in hypertension. In patients with borderline hypertension, indices of aortic distensibility are often altered, but are poorly related to the degree of septal hypertrophy, which is considered to be a marker of cardiac hypertrophy in this particular population. In patients with sustained essential hypertension, the degree of cardiac hypertrophy seems to correlate strongly with the increase in aortic rigidity. Dihydralazinelike substances are unable to modify arterial stiffness, whereas calcium-entry blockers and converting-enzyme inhibitors improve arterial stiffness when achieving the same degree of blood pressure reduction. Modifications in aortic rigidity must be considered in order to understand reversion of cardiac hypertrophy as a result of antihypertensive treatment.

Antihypertensive Agents↗
PubMed1987

[Index of arterial and venous compliance and echocardiographic parameters in essential permanent arterial hypertension].

Forearm venous tone (FVT), carotido-femoral pulse wave velocity (PWV), and left ventricular end diastolic diameter (LVD), left ventricular posterior wall thickness (LVPWT), myocardiac mass (MM), measured by echography were evaluated on 25 subjects with sustained essential hypertension and 30 normotensive subjects with same age and same sex. For the overall population, FVT is positively correlated with LVD (r = 0.45, p less than 0.001), with LVPWT (r = 0.37, p less than 0.01) and with MM (r = 0.55, p less than 0.001). PWV is not correlated with LVD but is positively correlated with LVPWT (r = 0.48, p less than 0.001) and with MM (r = 0.40, p less than 0.01). Stroke volume is positively correlated with FVT (r = 0.42, p less than 0.01), but not with PWV. This study shows that in a population of normals and sustained essential hypertensive subjects: i) indexes of venous compliance are correlated with myocardial thickness, myocardiac mass, left ventricular diameter and stroke volume, while ii) indexes of arterial compliance are only correlated with myocardial thickness. Thus, the modifications of arterial and venous compliance observed in sustained essential hypertension influence cardiac structure and function.

Adult↗
PubMed1987

[Hyperreactivity of the humeral artery to noradrenaline in essential hypertension patients].

The hyperresponsiveness of small arteries to norepinephrine is well documented in essential hypertensive patients. Our objective was to investigate in situ the reactivity to norepinephrine of the diameter of large arteries which are involved in the arterial disease of hypertension as well as small arteries. Brachial artery diameter, blood flow velocity, local volumic blood flow and local vascular resistances were determined non invasively using a pulsed Doppler system in 19 patients with essential hypertension and 9 normotensive subjects, before and after placebo (glucose) or increasing doses of norepinephrine (10, 20 and 40 ng/kg/min; i.v.) given in a single blind fashion. In hypertensive patients, norepinephrine (40 ng/kg/min) induced (i) a significant decrease in brachial artery diameter, local blood velocity, volumic flow and conductance and (ii) a small increase in mean arterial pressure. These hemodynamic changes did not occurred in the placebo group and were significantly greater in hypertensive patients than in normotensive subjects although plasma norepinephrine increased to the same extent in both groups. We conclude that in hypertensive patients, the increase in vascular reactivity to norepinephrine involves not only the resistive vessels, but also the large arteries thus decreasing their conducting and buffering function.

Adult↗
PubMed1987

Hemodynamic effects of the anti-hypertensive agent ketanserin in hypertension in man.

The hemodynamic changes caused by ketanserin, an anti-hypertensive agent with S2-serotonergic receptor and alpha 1-adrenoceptor blocking properties, are reviewed in patients with essential hypertension. The hemodynamic profile associates a decrease in total peripheral resistance, an unchanged cardiac output, and a modest reflex cardiac stimulation. Whether the drug reverses the other hemodynamic abnormalities of essential hypertension, such as reduced arterial and venous compliances and increased cardiac mass, remains largely unknown. Evaluation of the changes in arterial and venous systems will be important in the view that the pharmacological profile of ketanserin could be involved in the modifications of the arterial wall observed in hypertension and atherosclerosis.

Blood Pressure↗
PubMed1986

Enkephalins increase cyclic adenosine monophosphate content, calcium uptake, and contractile state in cultured chick embryo heart cells.

Peripheral vascular effects of opioid peptides are well known, but direct myocardial effects have not been established. We studied the inotropic response of spontaneously beating cultured chick embryo ventricular cells to the enkephalin analogue [D-Ala2]-enkephalin. Amplitude of cell motion increased in a concentration-dependent manner with 0.53 microM [D-Ala2]-enkephalin producing half-maximal response. The mechanism of this positive inotropic effect was investigated by examining alterations in 45Ca influx, cyclic AMP accumulation and adenylate cyclase activity in response to [D-Ala2]-enkephalin. At maximally inotropic concentrations, the 45Ca influx rate increased 39%, adenylate cyclase was stimulated by 30%, and cyclic AMP content rose more than twofold. Thus, in contrast to neural tissue, receptors for enkephalin in cultured heart cells are coupled to adenylate cyclase in a stimulatory manner. Occupancy of these receptors produces an increase in cyclic AMP levels and exerts a positive inotropic effect via a verapamil-sensitive enhancement of Ca influx.

1-Methyl-3-isobutylxanthine↗
PubMed1986

[Central cardiovascular effects of a calcium inhibitor, nifedipine, and a calcium channel activator, Bay k 8644, in the anesthetized rat].

The antihypertensive effect of calcium channel inhibitors (CCI) results mainly from their direct action on the vascular smooth muscle. However CCI may pass through the blood-brain barrier and may modulate central mechanisms involving calcium channels. Normotensive (WKY) and spontaneously hypertensive (SHR) (Okamoto) rats weighing 300 g were anaesthetized with pentobarbital (50 mg/kg i.p.) and ventilated. Mean arterial pressure (MAP) was measured from a catheter inserted into the femoral artery. Heart rate (HR) was electronically integrated. Vehicle (ethanol 95%), nifedipine and Bay k 8644 (Bay) were injected under a 1.5 microliter volume into the lateral ventricle of the brain (i.c.v.). Vehicle alone did not change significantly MAP or HR. The calcium-channel inhibitor nifedipine and the calcium-channel activator Bay had opposite effects, when i.c.v. injected: hypotension with bradycardia and hypertension without tachycardia, respectively. These effects are dose-dependent (5-50 micrograms/kg). They are of central origin since they are suppressed by ganglionic blockade by hexamethonium(100 mg/kg i.c.). Bilateral vagotomy suppressed the i.c.v.-nifedipine induced bradycardia. Previously i.c.v. administered nifedipine (5 micrograms/kg) suppressed the pressor response to Bay (5 micrograms/kg i.c.v.). Changes in MAP and HR are significantly more marked in SHR than in WKY. These results indicate that a calcium-channel inhibitor and a calcium-channel activator can modulate in opposite fashion central calcium-dependent mechanisms involved in blood pressure control.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1986

[Non-invasive study of the role of carotid distension in the baroreflex response to the arteriolar vasodilator cadralazine in essential hypertension].

Using pulsed Doppler methods, hemodynamics of the common carotid and the brachial arteries were measured in 10 patients with essential hypertension. After vasodilatation due to Cadralazine, a Dihydralazine-like substance, mean arterial pressure significantly decreased and heart rate increased. Change in PRA was significantly and positively correlated with the change in heart rate. In the brachial artery circulation, diameter and vascular resistance decreased while blood flow velocity and volumic blood flow did not increase significantly. In the common carotid artery circulation, diameter, mean blood flow did not change. However, vascular resistance and tangential tension decreased slightly. The increase in heart rate was strongly and negatively correlated (r = 0.82 p less than 0.01) with the change in the carotid artery tangential tension (measured as the product between mean arterial pressure and arterial radius) while no comparable correlation was observed with the change in blood pressure or arterial radius alone. The study suggested that in essential hypertensives, modifications in the carotid artery tangential tension secondary to arteriolar vasodilatation contribute actively to the baroreflex response.

Adult↗
PubMed1986

Common carotid blood flow in patients with hypertension and stenosis of the internal carotid artery.

Common carotid blood flow has been measured using pulsed Doppler techniques in hypertensive patients over 45 years of age, with and without stenosis of the internal carotid artery. In hypertensive patients without stenosis, arterial diameter remained within the normal range, whereas blood flow velocity and blood flow were significantly reduced. Vascular resistance was significantly increased but did not change markedly after administration of the vasodilating drug isosorbid dinitrate. Patients with hypertension and stenosis of the internal carotid artery were compared with two different populations used as controls: In comparison with hypertensive patients without stenosis of the internal carotid artery, both arterial diameter and blood flow velocity were reduced, leading to a more pronounced decrease in blood flow; and in comparison with normotensive patients with stenosis of the internal carotid artery, common carotid blood flow was more reduced at any degree of stenosis. In a subset of patients, blood flow returned toward normal ranges after endarterectomy. The study suggested that in patients with hypertension without stenosis of the internal carotid artery, the decrease in blood flow is due to a decrease in blood flow velocity with normal arterial diameter despite the elevated blood pressure, and in patients with hypertension and stenosis of the internal carotid artery, blood flow was more reduced than in the normotensive patients with stenosis of the internal carotid artery, suggesting that caution must be taken with indications of antihypertensive treatment.

Adult↗
PubMed1985

Enkephalins have a direct positive inotropic effect on cultured cardiac myocytes.

Enkephalins have peripheral vascular effects, and enkephalinergic innervation of the heart has been reported. To determine whether enkephalins have direct effects on myocardium, we studied the effects of [D-Ala2, Met5]enkephalinamide and [D-Ala2, D-Leu5]enkephalin on amplitude of contraction (measured with an optical-video system) in spontaneously beating monolayer cultures of chicken embryo ventricular cells, a preparation devoid of intact neural elements. [D-Ala2, Met5]enkephalinamide and [D-Ala2, D-Leu5]enkephalin as well as [Met5]- and [Leu5]enkephalin increased contractility in a concentration-dependent manner. The enkephalin-induced maximal contractile effects were 28% and 30% above control, with EC50 values of 0.53 and 0.17 microM for [D-Ala2, Met5]enkephalinamide and [D-Ala2, D-Leu5]enkephalin, respectively. The positive inotropic effect was antagonized by naloxone but not by propranolol, phentolamine, diphenhydramine, or cimetidine. Naloxone alone had no effect on contractility at a concentration (0.1 microM) that blocked positive inotropic effects of [D-Ala2, Met5]enkephalinamide and [D-Ala2, D-Leu5]enkephalin. To demonstrate the presence of opiate receptors, we studied [3H]naloxone binding in homogenates of cultured chicken embryo ventricular cells. Analysis of binding curves under equilibrium conditions indicated that [3H]naloxone bound specifically to membranes of cultured heart cells with KD = 18.5 +/- 5.4 nM and Bmax = 46.8 +/- 11.7 fmol/mg of protein. We conclude that enkephalins exert a direct positive inotropic effect on cultured heart cells, increasing contractile state via specific opiate receptors.

Animals↗
PubMed1985

Inotropic effect, binding properties, and calcium flux effects of the calcium channel agonist CGP 28392 in intact cultured embryonic chick ventricular cells.

CGP 28392 is a recently described dihydropyridine derivative with positive inotropic properties. To study the mechanism of action of this putative calcium channel agonist, we have related the effects of CGP 28392 on contraction (measured with an optical video system) and radioactive calcium uptake to ligand-binding studies in cultured, spontaneously beating chick embryo ventricular cells. CGP 28392 produced a concentration-dependent increase in amplitude and velocity of contraction (EC50 = 2 X 10(-7) M; maximum contractile effect = 85% of the calcium 3.6 mM response). Nifedipine produced a shift to the right of the concentration-effect curve for CGP 28392 without decreasing the maximum contractile response, suggesting competitive antagonism (pA2 = 8.3). Computer analysis of displacement of [3H]nitrendipine binding to intact heart cells by unlabeled CGP 28392 indicated a KD = 2.2 +/- 0.95 X 10(-7) M, in good agreement with the EC50 for the inotropic effect. CGP 28392 increased the rate of radioactive calcium influx (+39% at 10 seconds) without altering beating rate, while nifedipine decreased radioactive calcium influx and antagonized the CGP 28392-induced increase in calcium influx. Our results indicate that, in intact cultured myocytes, CGP 28392 acts as a calcium channel agonist and competes for the dihydropyridine-binding site of the slow calcium channel. In contrast to calcium channel blockers, CGP 28392 increases calcium influx and enhances the contractile state.

Animals↗
PubMed1985

Cardiopulmonary blood volume and plasma renin activity in man: preliminary report.

Cardiopulmonary blood volume (CPBV) and plasma renin activity (PRA) were measured simultaneously in five normal subjects and six patients with essential hypertension studied in the following different conditions: supine position, head-down tilt, thigh-cuffs inflation. In each individual, a significant negative correlation (r > or = 0.95) was observed between CPBV and PRA. The slope of the relationship (delta PRA/delta CPBV) was used as an index of sensitivity of the neural control of renin release through cardiopulmonary receptors of the low pressure system. Simultaneously, the sensitivity index of the high pressure baroreflex system (HPB) was evaluated using bolus injections of phenylephrine. In normal subjects and patients with hypertension, the delta PRA/delta CPBV ratio and HBP were strongly correlated. Both indices were negatively correlated to age. It is suggested that the sensitivity of the neural control of renin release as well as the arterial baroreflex sensitivity are influenced by age, and possibly the inflexibility of the vascular system.

Adult↗
PubMed1984

[Cardiotoxicity of anthracyclines].

The cardiotoxicity of the anthracyclines, of which doxorubicin is the leading drug, manifests itself in two ways: acutely, giving rise to temporary and usually benign phenomena, and chronically, giving rise to cardiac failure which is often irreversible. The risk of cardiomyopathy is related to the total dose of anthracycline administrated. The main risk factors are, age, previous cardiac disease and mediastinal radiotherapy. The prevention of cardiomyopathy is based on the respect of empirical guide lines (interruption of anthracyclines at "threshold" cumulative doses) and on methods of detection of infra-clinical disease. Myocardial angioscintigraphy which is easier to perform than myocardial biopsy and more sensitive and specific than echocardiography seems to be the investigation of choice. The main lines of research are aimed at improving our understanding of the mechanism of the cardiomyopathy, the institution of clinical trials to detect the first signs of toxicity of continuous infusions, the improvement of the standardisation and specificity of methods of detection, better definition of alarm thresholds and the development of new, less cardiotoxic, anthracyclines and cardioprotective agents.

Acute Disease↗
PubMed1983

Central cardiovascular effects of kappa agonists dynorphin-(1-13) and ethylketocyclazocine in the anaesthetized rat.

Opiate kappa agonists were administered into the cisterna magna of normotensive urethane-anaesthetized artificially ventilated rats: ethylketocyclazocine (78.7 nM) (EKC) and dynorphin-(1-13) (62.3 nM) produced significant and long-lasting decreases in both blood pressure and heart rate. High doses of naloxone (1 mg/kg i.v.) were required to partially antagonize these effects. The central cardiovascular effects of EKC and dynorphin-(1-13) were compared to those of fentanyl (3 nM), [D-Ala2,Met5]enkephalinamide (17 nM) and beta-endorphin (2.9 nM) which induced increases in blood pressure and heart rate. These results suggest that opposite central cardiovascular effects could be induced by activation of various opiate receptors.

Animals↗
PubMed1983

Estimation of forearm arterial compliance in normal and hypertensive men from simultaneous pressure and flow measurements in the brachial artery, using a pulsed Doppler device and a first-order arterial model during diastole.

Simultaneous brachial artery pressure and blood flow measurements were made in 45 men. Blood flow was evaluated by means of a pulsed Doppler device with a double transducer probe. From analysis of the pressure-flow curves during diastole, forearm arterial compliance (FAC) was determined by using the model of the forearm arterial tree as a system of tubes, each with a storage capacitance, in series with the arteriolar resistances vessels. The value of FAC for seven normal subjects, aged 44 +/- 3 (mean +/- SEM) years, was between 0.78 and 1.73 X 10(-10) m5 . N-1. By comparison, a 30% reduction in FAC was observed in 38 men of the same age with essential hypertension, which was similar whether the intra-arterial diastolic pressure was above or below 90 mmHg. In the more severe group (Intra arterial diastolic pressure greater than 90 mmHg), the reduced FAC was associated with a significant increase in brachial artery diameter; after administration of dihydralazine, blood pressure and arterial diameter returned to normal but FAC remained diminished. The study is the first to evaluate FAC in intact men. The reduced FAC in hypertension is independent of blood pressure "per se" but may reflect adaptive change in the walls of the large arteries. In the more severe hypertension, arterial calibre was increased; this could be a mechanism which could prevent FAC from decreasing further with chronic elevation of blood pressure.

Adult↗
PubMed1983

Opposite central cardiovascular effects of various morphine-like drugs and opiate peptides in the rat.

Opiate agonists were administered into the cisterna magna of normotensive urethane-anaesthetized artificially-ventilated rats. Increases in blood pressure and heart rate were produced by fentanyl (0.3-3.0 nmol). [D-ala]2-met-enkephalinamide (17 nmol), and beta-endorphin (2.9 nmol). On the contrary, ethylketocyclazocine (78.7 nmol) and dynorphin (1-13) (62.3 nmol) produced decreases in blood pressure and heart rate. The cardiovascular effects of ethylketocyclazocine and dynorphin (1-13) were antagonized by higher doses of naloxone than that required to counteract the effects of fentanyl. These results suggest that opposite central cardiovascular effects could be induced by activation of various opiate receptors.

Animals↗