Biomedical subjects

C Richer

Publications and source records attributed to C Richer.

At least 91 records · Page 5Linked to original sources

PubMed1987

[Atrial natriuretic factor. Systemic and regional hemodynamic profile and interaction with the alpha-adrenergic system in pithed SHR rats].

The hemodynamic effects of ANF (1 and 5 micrograms/kg/min) and its potential interactions with the sympathetic system were investigated at the systemic and regional (pulsed Doppler) levels in the pithed SHR. ANF dose-dependently decreased cardiac output CO, renal (RBF), mesenteric (MBF) and hindquarter (HQBF) blood flows and increased the corresponding vascular resistances: total peripheral (TPR), renal (RR), mesenteric (MR) and hindquarter (HQR), all these effects being significant at 5 micrograms/kg/min. Mean blood pressure (MBP) and heart rate were also significantly decreased at 5 micrograms/kg/min. ANF significantly reduced the responses to cirazoline of MBP, TPR and RR (1 microgram/kg/min) and of MR (5 micrograms/kg/min) but did not affect those of HQR ANF also significantly reduced the responses to UK-14,304 of MBP, TPR and MR (5 micrograms/kg/min) but did not affect those of RR and HQR. These data indicate that (a) ANF, in the absence of reflex phenomenons, exerts intrinsic regional vasoconstrictor effects, (b) ANF exhibits a postsynaptic sympatho-inhibitory effect. The latter is more marked vs the alpha 1-(especially renal) than vs the alpha 2-adrenoceptor-mediated responses but does not affect the hindquarter vascular bed, which suggest that its contribution to the overall antihypertensive action of ANF is of limited importance.

Animals↗

PubMed1986

Systemic and regional pre- and post-junctional sympathoinhibitory effect of perindopril in spontaneously hypertensive rats.

The interaction between converting enzyme inhibition and sympathetic system activity at systemic and regional (renal, mesenteric, hindlimb) levels was investigated in adult pithed spontaneously hypertensive rats (SHR) using perindopril (5 mg/kg orally every day for 8 days) and the pulsed Doppler technique. Perindopril induced a decrease in systolic blood pressure and in regional vascular resistance which was abolished by binephrectomy. In addition, the drug had a sympathoinhibitory effect on the systemic vasopressor and the regional vasoconstrictor responses to cirazoline, especially UK 14304, an effect which was kidney-dependent (abolished by binephrectomy) and postjunctional, and spinal cord stimulation, an effect which was kidney-independent and most likely prejunctional in its mechanism.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1986

[Peripheral hemodynamic and biological effects of perindopril in the healthy subject. Dose-effect relationship].

The effects of three doses of perindopril (4.8 and 16 mg), a new angiotensin I-converting enzyme inhibitor, and of a placebo on systemic blood pressure, heart rate, brachial artery flow and diameter, forearm vascular resistance and the renin angiotensin system biological parameters (plasma converting enzyme activity PCEA, renin activity PRA and aldosterone PA) were compared during a double-blind cross-over study performed in six healthy volunteers. Perindopril dose-dependently inhibited PCEA, increased PRA, augmented brachial artery flow and diameter and decreased forearm vascular resistance, whereas it did not affect systemic blood pressure and heart rate. The perindopril-induced increase in brachial artery flow was related (a) at the low dose to the sole arteriolar and (b) at the two highest doses to both arteriolar and large vessels dilatation. Finally, during the ten first hours following drug intake, there was a significant correlation between perindopril-induced PCEA inhibition and brachial artery flow increase.

Adult↗

PubMed1985

Beta-adrenoceptor blocking effects and plasma levels of bornaprolol and propranolol in man.

The beta-adrenoceptor blocking effects and pharmacokinetics of bornaprolol (FM 24), a new beta-adrenoceptor blocking agent, have been compared with those of propranolol and a placebo in a double-blind trial in 6 healthy volunteers. Heart rate, systolic and diastolic blood pressures and peak expiratory flow rate were measured at rest and at the end of 3 min vigorous exercise on a bicycle ergometer, before and 2,24 and 48 h after single oral doses of bornaprolol (120, 240 and 480 mg) and propranolol (40, 80 and 160 mg). Plasma renin activity at rest and the plasma concentrations of the two drugs were determined. Bornaprolol significantly reduced resting heart rate, dose-dependently lowered exercise-induced tachycardia and decreased peak expiratory flow rate and plasma renin activity. In addition, exercise-induced tachycardia was significantly reduced by bornaprolol up to 48 hours after drug intake (pharmacodynamic half-life approximately 63-86 h) and there was a correlation between this reduction and the log plasma bornaprolol concentration over the 48-h period. Thus, bornaprolol behaved in man as a non-cardioselective and long-lasting beta-adrenoceptor blocking drug, probably devoid of intrinsic sympathomimetic activity.

Adult↗

PubMed1985

The effect of enalapril on baroreceptor mediated reflex function in normotensive subjects.

The effects of enalapril, 20 mg orally, on the responses to baroreflex activation and deactivation by respectively phenylephrine and nitroglycerin were investigated in normotensive subjects on a normal sodium diet, with simultaneous measurement of plasma renin activity (PRA), converting enzyme activity (PCEA), aldosterone and catecholamines. Enalapril, 4 h after administration, lowered artificial blood pressure without modifying heart rate and plasma catecholamines. PCEA was abolished, PRA increased and plasma aldosterone decreased. Enalapril (a) displaced to the left the baroreflex set-point, (b) did not affect baroreflex sensitivity since the slopes of the RR-interval/systolic blood pressure regression lines remained unchanged during both activation and deactivation and (c) did not modify baroreflex efficacy since the maximal RR-interval responses as well as the overall RR-interval-time products to identical blood pressure variations were not modified. Thus, enalapril induced a resetting of the baroreflex, which probably accounts for the lack of reflex tachycardia observed during the drug-induced fall in blood pressure.

Adult↗

PubMed1984

Attenuation by diltiazem of arterial baroreflex sensitivity in man.

The effect of oral diltiazem 120 mg, on the responses to baroreflex activation and deactivation by phenylephrine and nitroglycerin, respectively, were investigated in normotensive subjects, with simultaneous measurement of plasma catecholamine levels. Diltiazem significantly reduced the tachycardia induced by bolus injections of nitroglycerin and abolished the concomitant increase in plasma noradrenaline. It also significantly decreased the bradycardiac response to phenylephrine infusion. Diltiazem reduced, although not significantly so, the bradycardia induced by boluses of phenylephrine. The overall reduction in baroreflex sensitivity, which might contribute to the limited tachycardiac effect of diltiazem in man, is consistent with the drug-induced attenuation of the sympathetic and also of the parasympathetic components of the baroreceptor reflex.

Adolescent↗

PubMed1984

Captopril: pharmacokinetics, antihypertensive and biological effects in hypertensive patients.

The kinetics of captopril plasma levels and of the drug-induced plasma converting enzyme activity (PCEA), plasma renin activity (PRA) and diastolic blood pressure (DBP) modifications were studied over 24 h after oral administration of captopril, 1 mg/kg, to ten hypertensive patients. Free unchanged captopril pharmacokinetic parameters were: t1/2, alpha: 0.45 +/- 0.06 h; tmax: 0.98 +/- 0.13 h; Cmax: 1.31 +/- 0.20 mg l-1; t1/2,z: 0.66 +/- 0.13 h; V: 0.614 +/- 0.104 1 kg-1 and CLtot: 0.690 +/- 0.082 l h-1 kg-1. At 6 h captopril was no longer detectable in plasma. The onset of PCEA inhibition and of DBP decrease closely followed the rise of captopril's plasma levels, while that of PRA increase was delayed. In contrast, while captopril rapidly disappeared from plasma, its biological and antihypertensive effects were long-lasting. The lack of correlation between the relative bioavailability of captopril and the induced reduction in DBP (evaluated by the corresponding AUCs) suggests that free unchanged captopril plasma monitoring is not an adequate indicator of hypertensive patients' potential responsiveness to captopril's blood pressure lowering effects.

Adult↗

PubMed1984

Influence of chronic renal failure on captopril pharmacokinetics and clinical and biological effects in hypertensive patients.

The pharmacokinetic parameters of unchanged plasma captopril and the kinetics of the drug effects on plasma converting enzyme activity (PCEA), plasma renin activity (PRA), plasma aldosterone (PA) and mean blood pressure (MBP) were studied over 24 h after oral administration in three groups of hypertensive patients: with normal renal function (group 1, plasma creatinine less than 110 mumol/l, n = 10), with moderate chronic renal failure (group 2, 135 less than plasma creatinine less than 450 mumol/l, n = 10) and with severe chronic renal failure (group 3, plasma creatinine greater than 500 mumol/l, n = 10). Renal impairment had no effect on plasma captopril Cmax, CLtot and relative bioavailability (AUC). In contrast, captopril kel decreased while T1/2 increased progressively from group 1 to group 3. PCEA blockade (T1/2 and AUC) was increased significantly and proportionally to the degree of renal impairment. However, there were no differences between the three groups regarding captopril-induced modifications of PRA and PA. Although the maximal reduction in MBP was identical in the three groups, the overall antihypertensive effect (AUC) of captopril increased significantly and progressively from group 1 to group 3, especially in duration. There was no correlation between basal plasma creatinine values and unchanged captopril relative bioavailability (AUC) and between unchanged captopril relative bioavailability (AUC) and the drug effects (AUC) on PCEA, PRA, PA and MBP. However there was a correlation between basal plasma creatinine values and plasma captopril T1/2, PCEA blockade (AUC) and overall antihypertensive effect (AUC). The apparent discrepancy between the lack of effects of chronic renal failure on plasma unchanged captopril bioavailability and its potentiating effects on PCEA blockade and MBP reduction may be accounted for by the renal impairment-induced accumulation of captopril metabolites.

Adult↗

PubMed1984

Serum angiotensin I-converting enzyme activity in premature and full-term infants.

Serum angiotensin I-converting enzyme activity (SCEA) was investigated in 15 healthy premature (gestational age ranging from 30 to 36 weeks) and in 14 healthy full-term (gestational age ranging from 37 to 41 weeks) newborns as well as in 16 healthy adults (32.0 +/- 2.6 years). SCEA mean values in the three groups, respectively, 23.3 +/- 1.3, 24.4 +/- 1.6 and 23.2 +/- 1.7 nM . min-1 . ml-1, did not differ significantly from each other and in the newborns there was no correlation between SCEA values and gestational age.

Gestational Age↗

PubMed1984

[Effect of renal insufficiency on the pharmacokinetics of captopril and converting enzyme inhibition in the hypertensive patient].

The influence of renal insufficiency (RI) on the pharmacokinetics of captopril (1 mg/kg, orally) and on the kinetics of the induced converting enzyme inhibition (CEI) was investigated in three groups of hypertensive patients: without RI (n = 10, plasma creatinine less than 100 mumol/l), with moderate RI (MRI) (n = 10,200 less than creatinine less than 400 mumol/l) and with severe RI (SRI) (n = 8, creatinine greater than 500 mumol/l). Captopril pharmacokinetic parameters were not modified by RI, with the exception of elimination half-life which was lengthened, but relative bioavailability of the drug was not modified. In contrast, captopril-induced CEI was strongly potentiated in patients with RI, an effect correlated with plasma creatinine values. This apparent discrepancy between the lack of modification in captopril plasma bioavailability and the prolongation of its biological effects can probably be accounted for by a decreased elimination and/or an increased formation of captopril metabolites during RI.

Adult↗

PubMed1984

Pharmacological, hemodynamic and autonomic nervous system mechanisms responsible for the blood pressure and heart rate lowering effects of pergolide in rats.

In conscious spontaneously hypertensive rats, pergolide (50.0 micrograms/kg s.c.) produced a sustained decrease in tail artery pressure which was blocked by haloperidol (1.0 mg/kg s.c.) pretreatment. In anesthetized spontaneously hypertensive rats this effect was accompanied by a fall in total peripheral resistance inasmuch as pergolide did not significantly change cardiac output. In anesthetized normotensive rats, pergolide (30.0 micrograms/kg i.v.) also lowered blood pressure. This effect was not significantly modified by adrenalectomy, methysergide, idazoxan (alpha-2 adrenoceptor antagonist), vagotomy alone or plus ligation of carotid arteries or plus atenolol, but was entirely prevented by domperidone or sulpiride pretreatment and was reverted to a pressor response (due to stimulation of alpha adrenoceptors and 5-hydroxytryptamine receptors) by blockade of ganglionic transmission with chlorisondamine. Pergolide given either i.v. or into the cisterna magna or the lateral cerebral ventricle produced changes in blood pressure of the same magnitude. In intact or adrenalectomized rats, i.v. pergolide significantly lowered plasma norepinephrine concentration. Furthermore, in saline but not sulpiride-pretreated pithed rats, pergolide reduced the pressor responses and the accompanying increases in plasma norepinephrine evoked by electrical stimulation of the spinal cord. However, pergolide failed to modify the vascular reactivity to several pressor agents and lacked beta-2 and DA-1 dopamine receptor agonist properties. These results indicate that the decrease in blood pressure produced by pergolide can be accounted for by an inhibition of sympathetic tone resulting from stimulation of peripheral neuronal dopamine receptors. A possible central contribution remains to be substantiated. The pronounced bradycardia produced by pergolide (30.0 micrograms/kg i.v.) in anesthetized intact rats was partly reduced by vagotomy, methylatropine, domperidone, sulpiride, idazoxan, phentolamine or atenolol. The effects of pergolide in vagotomized rats were further diminished by domperidone but they were blocked by the combination of phentolamine or idazoxan plus domperidone. In rats pretreated with atenolol or in rats with the cervical section of spinal cord and the low level of heart rate increased with an isoprenaline infusion, the decrease in heart rate produced by pergolide was abolished by domperidone, methylatropine or idazoxan. In pithed rats, pergolide changed neither the base-line heart rate nor the tachycardia to exogenous norepinephrine nor the bradycardia evoked by carbachol or electrical stimulation of the peripheral cervical vagus.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenalectomy↗

PubMed1983

Postsynaptic alpha adrenoceptors and attenuation of vascular sympathetic responses in SHRs by captopril and enalapril.

The effects of a short-term oral treatment with captopril or enalapril, two converting enzyme inhibitors (CEIs) administered in equipotent antihypertensive doses, on the systemic vasopressor and on the renal, mesenteric and hind-limb vascular responses to cirazoline and UK 14304, respectively alpha1- and alpha2- adrenoceptor specific agonists, were investigated in the adult pithed SHR. Cirazoline and UK 14304 induced vasoconstrictor responses in the three investigated territories, demonstrating the location and a functional role at these levels of the two sub-types of alpha-adrenoceptors. Both captopril and enalapril reduced, to the same extent, the systemic pressor and the regional vasoconstrictor responses, especially in the renal and mesenteric territories, elicited by cirazoline and UK 14304, demonstrating that both subtypes of alpha-adrenoceptors are involved in the CEIs-induced attentuation of sympathetic responses.

Animals↗

PubMed1982

MK 421 and prevention of genetic hypertension development in young spontaneously hypertensive rats.

MK 421, at the dose of 25 mg/kg, administered daily by gavage to spontaneously hypertensive rats (SHRs) from their 4th to 15th weeks of age almost completely inhibited development of genetic hypertension. Since heart rate and cardiac and systolic indexes were not affected by the drug, prevention of genetic hypertension development was solely related to an early, potent and long-lasting reduction of the progressive increase of the peripheral resistance which generally develops in SHRs during ageing. MK 421 reduced body growth but did not modify fluid intake, plasma NA+ and urine volume, thus water and salt retention did not develop. MK 421 enhanced vascular responsiveness to norepinephrine and angiotension II and reduced myocardial hypertrophy. Plasma renin concentration was increased and urinary antidiuretic hormone did not change. Finally, MK 421's preventive effects against genetic hypertension development persisted up to 10 weeks after discontinuation of treatment.

Aging↗

PubMed1982

Theophylline kinetics and ventilatory flow in bronchial asthma and chronic airflow obstruction: influence of erythromycin.

The kinetics and the effects on the ventilatory function peak expiratory flow rate (PEFR) of a single 600-mg oral dose of theophylline were investigated in 46 adult patients with bronchial asthma (BA) and in 16 adult patients with chronic airflow obstruction (CAO). In the former, theophylline induced an early and potent bronchodilatation (60% rise in PEFR), the kinetics of which correlated with plasma concentration. Theophylline was also effective in patients with CAO, but the magnitude of its bronchodilator effect was less than in those with BA: this was despite plasma concentrations of much the same order. In adult patients with BA (but not with CAO) theophylline plasma levels and bioavailability are higher after simultaneous erythromycin dosing.

Adult↗

PubMed1982

[Prevention of the development of genetic hypertension by MK 421 in the SHR].

MK 421, 25 mg/kg, administered daily by gavage to young spontaneously hypertensive rats (SHRs) from their 4th to 15th weeks of age almost completely inhibited genetic hypertension development. Since heart rate and cardiac index were not drug affected, prevention of genetic hypertension development was solely related to an early, potent and long-lasting limitation of the progressive increase in peripheral resistance which normally develops in SHRs during ageing. MK 421 slightly enhanced vascular responsiveness to exogenous norepinephrine and angiotensin II and reduced myocardial hypertrophy. Plasma renin concentration was increased. MK 421 slightly reduced body growth but did not affect fluid intake, urinary volume and urinary ADH, demonstrating that no water or salt retention developed. Finally, MK 421's preventive effects against genetic hypertension development persisted up to 10 weeks after treatment discontinuation.

Angiotensin II↗

PubMed1981

[Preventive effect of captopril on the development of genetic hypertension in SHR rats (author's transl)].

Captopril, an inhibitor of the angiotensin-converting enzyme, is very effective in preventing the development of genetic hypertension in SHR rats. This effect results from early, overall lowering of local vascular resistances and, consequently, suppression of the age-related increase in total peripheral resistance. Contrary to that of dihydralazine and atenolol, it persists for up to 12 weeks after the drug is discontinued. Captopril may act by inhibiting the angiotensin-converting enzyme present in the vascular wall, with subsequent temporary arrest of the vascular lesions associated with progressive genetic hypertension.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1981

Immediate effects of captopril in acute left ventricular failure secondary to myocardial infarction.

In eight patients with acute left ventricular failure secondary to myocardial infarction the haemodynamic effects of captopril (25 mg), an orally active converting enzyme inhibitor, were measured. Haemodynamic modifications were maximal at 60 min and lasted for 2-3 h. Pulmonary wedge pressure fell from 23.5 +/- 4.9 (mean +/- SD) to 16.8 +/- 4.7 mmHg (P less than 0.01), cardiac output rose from 3.24 +/- 1 to 4.05 +/- 0.91 1/min (P less than 0.01). Systemic vascular resistance decreased from 27.34 +/- 3.81 to 17.52 +/- 1.65 mmHg min l-1 (P less than 0.01). Mean arterial pressure fell from 89.6 +/- 13.9 to 75.7 +/- 16.3 mmHg (P less than 0.001) while heart rate was not significantly modified. Six patients who had high pretreatment plasma renin activity values responded by a decrease in ventricular filling pressure and/or an increase in cardiac output. One patient with normal initial plasma renin activity value showed similar haemodynamic effects. THese data suggest that in the short term captopril is a vasodilator with both arterial and venous effects and improves cardiac function in acute left ventricular failure secondary to myocardial infarction.

Acute Disease↗

PubMed1981

[Comparison of the effects of betablockers and captopril on the development of genetic hypertension in the rat].

The preventative effects of betablockers and captopril on the development of genetic hypertension in genetically hypertensive rats, were studied after long-term daily dosage by forced feeding, from the 5th to the 20th week of age of the animals. Of the drugs studied, captopril, atenolol and propranolol limited the development significantly, but pindolol only had a modest effect and acebutolol was ineffective. No correlation was found between the degree of prevention of genetic hypertension and the intensity of betablockade. Atenolol and propranolol prevent genetic hypertension by I) reducing cardiac output, a reduction which is not neutralised by the simultaneous change in peripheral resistance, 2) decreasing plasma renin concentrations, and 3) limiting the development of myocardial hypertrophy. Captopril is very effective in preventing the development of genetic hypertension and acts: 1) by causing an early and lasting fall in peripheral resistance related to the suppression of Angiotensin II, and possibly by potentialising the vasodilatation of bradykinins and, 2) by limiting myocardial hypertrophy.

Adrenergic beta-Antagonists↗