Biomedical subjects

J F Giudicelli

Publications and source records attributed to J F Giudicelli.

At least 91 records · Page 5Linked to original sources

PubMed1993

Arterial hemodynamics and cardiac effects of enoximone, dobutamine, and their combination in severe heart failure.

The acute systemic and regional hemodynamic effects of dobutamine (5, 10, and 15 micrograms/kg/min intravenously), of enoximone (1, 1.5, and 2 mg/kg intravenously), and of the dobutamine-enoximone combination were compared in eight patients with severe congestive heart failure. Dobutamine and enoximone similarly and dose-dependently increased cardiac index and decreased systemic vascular resistance, right atrial pressure, and mean capillary wedge pressure. Dobutamine, but not enoximone, increased heart rate after 10 and 15 micrograms/kg/min. The combination of the two drugs caused a greater increase in cardiac index and a greater decrease in total peripheral resistance than did each drug alone. In the forearm vascular bed, brachial blood flow and brachial artery diameter were increased by enoximone significantly and dose-dependently and by dobutamine only at 5 micrograms/kg/min. Finally, the combination of the two drugs increased brachial blood flow but not brachial artery diameter to a larger extent than enoximone alone. Hepatosplanchnic and renal blood flows were not altered by any of the treatments. These results indicate that (1) enoximone exerts a significantly greater muscular vasodilator action than dobutamine; (2) the dobutamine-enoximone combination potentiates the systemic and brachial vasodilator effects of each drug; and (3) high doses of dobutamine (10 and 15 micrograms/kg/min) improve hemodynamics through their positive inotropic and chronotropic effects, whereas at low doses (5 micrograms/kg/min) a peripheral vasodilation also contributes.

Adult↗

PubMed1993

Regional hemodynamic effects of perindopril in congestive heart failure.

The onset of heart failure is associated with complex neurohumoral, cardiac, and vascular changes. These disorders partly explain that, in this situation, regional distribution of blood flows is hardly modified with stability or increase in heart and brain flows and impairement of limb, renal, and splanchnic blood flows. Using the bidimensional Doppler technique to measure brachial blood flow and diameter and standard clearance techniques to determine renal and hepatic blood flows, we studied the effects of perindopril, a long-lasting angiotensin-converting enzyme inhibitor, on regional hemodynamics. We demonstrated that perindopril produces a very marked increase in forearm and kidney flows but a very minor increase in the hepatosplanchnic territory, resulting in a regional distribution of cardiac output that favors the renal and musculocutaneous territories. This mechanism of action might be an important contribution to clinical improvement observed with perindopril.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1993

Repeatability of transcranial Doppler measurements of arterial blood flow velocities in healthy subjects.

1. Transcranial Doppler measurements of the mean blood flow velocity and the resistance index in the middle cerebral artery are used to assess cerebral haemodynamics. The prerequisite for the use of these parameters in clinical pharmacology studies is an evaluation of their repeatability and spontaneous variation with time. 2. Repeatability of transcranial Doppler measurements of mean blood flow velocity and resistance index was investigated in healthy subjects by calculation of the repeatability coefficient as defined by the British Standards Institution. Intra-observer repeatability (comparison of two successive determinations by one observer, n = 30 subjects), between-observer repeatability (comparison of two successive measurements each performed by a different observer, n = 30) and long-term repeatability (comparison of two determinations performed at the same hour with a 1 week interval by one observer, n = 14) were assessed. In addition, the spontaneous evolution with time of mean blood flow velocity and resistance index was determined over an 8 h period (n = 14). 3. Repeatability coefficients for intra-observer repeatability, between-observer repeatability and long-term repeatability were 4.83, 4.59 and 3.32 cm/s for mean blood flow velocity (normal value = 61.2 +/- 10.2 cm/s) and 2.62, 3.12 and 3.49% for resistance index, respectively (normal value = 53.6 +/- 5.9%), indicating that transcranial Doppler measurements are repeatable enough to be used over periods of time of up to 1 week in clinical pharmacology studies. 4. Finally, a time effect was detected for mean blood flow velocity, indicating that this parameter undergoes diurnal variation.

Adult↗

PubMed1993

Quinapril prevents stroke both during and after the treatment period in stroke-prone spontaneously hypertensive rats.

The effects of long-term oral administration of quinapril on the occurrence of stroke and on mortality were investigated in young salt-loaded stroke-prone spontaneously hypertensive rats (SHR-SPs) during the treatment period (8th-34th week of age) and up to 6 weeks thereafter. Simultaneously, blood pressure, saline intake, diuresis, and proteinuria were investigated at regular intervals, and cerebrovascular, renal, and cardiac lesions were assessed after death. Untreated SHR-SPs served as controls. Quinapril completely suppressed stroke and mortality, afforded only limited protection v blood pressure rise, and prevented any increase in saline intake, diuresis, and proteinuria both during and after the treatment period. Quinapril long-lastingly prevented vascular fibrinoid necrosis development at the cerebral, but also at the renal and cardiac levels. In the kidneys, vascular intimal and medial hyperplasia were strongly reduced, as were the glomerular and tubulo-interstitial lesions. At the cardiac level, intimal and medial hyperplasia were slightly reduced but infarction and fibrosis were hardly affected. As the renin-angiotensin system is highly stimulated in SHR-SPs and as angiotensin II (AII) is responsible for fibrinoid necrosis formation, vessel obstruction, and stroke in these animals, we conclude that the long-lasting protection afforded by quinapril v stroke and mortality in SHR-SPs both during and after the treatment period is mostly due to the drug-induced interruption of the renin-angiotensin system.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

PubMed1993

Differential effects of celiprolol and atenolol on large epicardial coronary arteries in conscious dogs at rest and during exercise.

The effects of celiprolol (1 mg/kg), a selective beta 1-adrenoceptor antagonist with partial agonist activity (PAA), on large and small coronary arteries and on systemic hemodynamics were investigated and compared with those of atenolol (1 mg/kg) and saline at rest and during three levels of treadmill exercise in the same 7 conscious dogs. Control exercise after saline administration induced increases in heart rate (HR 131 +/- 4%), left ventricular (LVdP/dt 117 +/- 5%), coronary blood flow (CBF 133 +/- 13%), and circumflex artery diameter (CxAD, 6.6 +/- 1.3%) and a decrease in coronary vascular resistance (CVR, -47 +/- 3%). Atenolol decreased LVdP/dt (-19 +/- 2%) and CxAD (-3.2 +/- 0.3%, p < 0.05) at rest, but large epicardial coronary arteries remained constricted during exercise (-4.7 +/- 1.4% at 12 km/h, p < 0.05) despite simultaneous dilation of coronary resistance vessels. In contrast to atenolol, celiprolol did not constrict large coronary arteries at rest (CxAD -0.2 +/- 0.9%, NS), and this beneficial effect of celiprolol was maintained throughout the exercise period. LVdP/dt was not modified and HR was slightly increased (14.3 +/- 2.6%) at rest by celiprolol. Atenolol and celiprolol reduced the exercise-induced positive inotropic and chronotropic effects, atenolol being the most potent. Thus, in dogs at rest when basal sympathetic tone was low, celiprolol, most likely because of its PAA, induced slight cardiac stimulation and prevented vasoconstriction of the large coronary arteries usually observed after beta-adrenoceptor blockade.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Systemic and coronary effects of the angiotensin II receptor antagonist EXP3174 in dogs.

The effects of EXP3174 (0.03-0.3 mg/kg), the active metabolite of the angiotensin II (AII) receptor antagonist losartan, on systemic and coronary hemodynamics as well as on regional myocardial blood flow (radioactive microspheres) were evaluated in anesthetized, open-chest dogs with or without preactivated renin-angiotensin system (RAS) (furosemide treatment). These effects were compared with those of the angiotensin-converting enzyme (ACE) inhibitor enalaprilat (0.1-1 mg/kg). In dogs without preactivated RAS, EXP3174 or enalaprilat did not exert marked hemodynamic effects other did not exert marked hemodynamic effects other than a significant decrease in mean arterial blood pressure (MAP) at the highest doses. In dogs with preactivated RAS, EXP3174 induced a marked, dose-dependent decrease in MAP (maximum decrease -23 +/- 7%), associated with a significant decrease in total peripheral resistance (TPR), whereas cardiac output (CO), heart rate (HR), and left ventricular dP/dt remained unchanged. At the coronary level, EXP3174 induced a decrease in mean coronary resistance that paralleled that of AP. Similar systemic and coronary hemodynamic effects were obtained with enalaprilat administered at doses three times higher. However, regional myocardial tissue perfusion, assessed by the microspheres technique (whether subendocardial, subepicardial, or transmural) or its transmural distribution (endo/epi ratios) was not affected by EXP3174 or enalaprilat. Thus, these results indicate that blockade of the AT1 receptor of AII by EXP3174 induces hemodynamic modifications similar to those evoked by the ACE inhibitor enalaprilat. The lack of effect of EXP3174 or enalaprilat on regional myocardial blood flow (RMBF) suggests, however, that the RAS does not play a role in regulation of myocardial tissue perfusion.

Angiotensin I↗

PubMed1993

Sympathoinhibitory effects of losartan in spontaneously hypertensive rats.

Nonselective inhibition of endogenous angiotensin II (AII) by AI-converting enzyme inhibitors (ACEI) results in sympathoinhibitory effects. We wished to examine the influence of selective inhibition of endogenous AII by losartan, a nonpeptide AT1-receptor antagonist, on the sympathetic system. Cardiac, systemic, and regional vascular (kidney, mesentery, hindlimb) responses to selective alpha 1- and alpha 2-adrenoceptor agonists and to electrical stimulation of the spinal cord were investigated in pithed spontaneously hypertensive rats (SHR) by pulsed Doppler technique. Losartan (10 mg/kg) was administered orally, either as a single dose or for 8 successive days. Under both conditions, AII systemic pressor, regional vasoconstrictor, and tachycardic responses were completely abolished by losartan. At the vascular level, losartan did not affect postsynaptic alpha 1-adrenoceptor-mediated systemic pressor and regional vasconstrictor responses, but reduced postsynaptic alpha 2-adrenoceptor-mediated renal vasoconstriction. Losartan significantly decreased the systemic pressor and regional vasoconstrictor responses elicited by spinal cord stimulation. This sympathoinhibitory effect was not homogeneously distributed, preferentially affecting the kidney. At the cardiac level, spinal cord stimulation induced a strong tachycardia which remained unaffected by losartan. Thus in SHR, losartan exerts sympathoinhibitory effects against the vascular but not the cardiac responses to spinal cord stimulation. Because the vascular responses to postjunctional alpha 1- and alpha 2-adrenoceptor stimulation, except in the kidney, simultaneously remain poorly affected, the sympathoinhibitory effects of losartan mainly develop prejunctionally through AT1-receptors blockade.

Adrenergic alpha-Agonists↗

PubMed1993

Losartan's protective effects in stroke-prone spontaneously hypertensive rats persist durably after treatment withdrawal.

The effects of long-term oral administration of losartan on the occurrence of stroke and on mortality were investigated in young salt-loaded stroke-prone spontaneously hypertensive rats (SHR-SPs) during the treatment period (5-20 weeks of age) and up to 8 weeks thereafter. Two doses of losartan, 1 and 10 mg/kg/day, were investigated, which afforded no and only moderate antihypertensive effects, respectively. During the treatment period, losartan at both doses completely suppressed stroke and mortality and strongly opposed (low dose) or abolished (high dose) the increases in saline intake, diuresis, and proteinuria observed in controls. It markedly limited (low dose) or abolished (high dose) vascular fibrinoid necrosis formation in the brain, kidneys, and heart. Finally, losartan, especially at the high dose, reduced arterial thickening and glomerular and tubulo-interstitial lesions in the kidneys, as well as arterial thickening, infarction, and fibrosis in the heart. Eight weeks after treatment discontinuation, all animals but one (low dose) were still alive. Vascular fibrinoid necrosis development remained strongly prevented (low dose) or fully suppressed (high dose) in all investigated organs. Finally, cardiac and renal lesions tended to worsen, and proteinuria was noted only in the low-dose group. We conclude that in SHR-SPs, angiotensin II, through AT1 receptor stimulation, most likely plays a major role in fibrinoid necrosis formation, vascular proliferative changes, and stroke occurrence and that losartan, most likely independently of its effect on blood pressure, affords a full and long-lasting protection against stroke and mortality both during and after the treatment period.

Aging↗

PubMed1993

Effects of an angiotensin-converting enzyme inhibitor, lisinopril, on cerebral blood flow autoregulation in healthy volunteers.

The effects of a single oral dose (20 mg) of lisinopril on systemic, carotid (pulsed Doppler), and cerebral (middle cerebral artery, transcranial Doppler) hemodynamics have been investigated over an 8-h period in eight healthy volunteers in a double-blind placebo-controlled crossover study. In addition, cerebral vasodilatory reserve was measured (acetazolamide test). Lisinopril did not affect systemic hemodynamics but it increased both common carotid artery blood flow (+26.2%, p < 0.01) and diameter (+4.5%, p < 0.05) after 8 h. Lisinopril did not affect middle cerebral artery mean blood flow velocity but increased cerebral resistance index (+8.1%, p < 0.05) at 4 h and cerebral vasodilatory reserve (+24.8%, p < 0.05). These data suggest that lisinopril produces a paradoxical vasoconstriction of the small cerebral arterioles. This vasoconstriction might be a compensatory mechanism to a dilation of large cerebral arteries, thus resulting in an unchanged cerebral blood flow.

Acetazolamide↗

PubMed1993

Alpha 1 and alpha 2-adrenergic control of large and small coronary arteries during exercise in conscious dogs under beta-blockade.

The aim of this study was to determine the relative roles of alpha 1-and alpha 2-adrenoceptors at the level of large epicardial and small resistance coronary arteries when sympathetic tone is increased by exercise in conscious dogs. The responses of left circumflex coronary artery diameter and blood flow were investigated at rest and during graded treadmill exercise (5, 10 and 12 km/h) in six chronically instrumented dogs during control conditions (saline) and after administration of propranolol (1 mg/kg) either alone or in combination with either prazosin (50 micrograms/kg), or idazoxan (300 micrograms/kg), or the association of prazosin+idazoxan (same doses). In control conditions, graded treadmill exercise resulted in a progressive increase in coronary artery diameter (+3.8 +/- 0.6% from 3479 +/- 80 microns) and in a decrease in coronary vascular resistance (-46.0 +/- 4.5% from 8.49 +/- 1.51 mmHg/cm/s). Propranolol significantly constricted large (-4.4 +/- 0.6% from 3486 +/- 87 microns) and limited dilation of small coronary arteries during exercise. These coronary effects of propranolol remained unchanged following additional alpha 2-adrenoceptor blockade by idazoxan but were abolished following alpha 1-adrenoceptor blockade by prazosin, given either alone or combined with idazoxan. Thus, alpha 1- but not alpha 2-adrenoceptors are responsible for propranolol-induced constriction of large coronary arteries and limitation of small coronary arteries dilation during exercise in conscious dogs.

Adrenergic beta-Antagonists↗

PubMed1993

Comparison of the effects of EXP3174, an angiotensin II antagonist and enalaprilat on myocardial infarct size in anaesthetized dogs.

1. In order to determine whether the renin-angiotensin system is involved in myocardial ischaemia-reperfusion injury, we investigated and compared the effects on infarct size of two different drugs which interfere with this system, i.e., an angiotensin II (AT1) antagonist, EXP3174, and an angiotensin I-converting enzyme inhibitor (ACEI), enalaprilat in a canine model of ischaemia-reperfusion. 2. EXP3174 (0.1 mg kg-1, i.v. followed by 0.02 mg kg-1 h-1 for 5.5 h) and enalaprilate (0.3 mg kg-1, i.v. followed by 0.06 mg kg-1 h-1 for 5.5 h) were used in doses inducing a similar level of inhibition (87 +/- 4 and 91 +/- 3%, respectively) of the pressor responses to angiotensin I. Control animals received saline. 3. Infarct size and area at risk were quantified by ex vivo dual coronary perfusion with triphenyltetrazolium chloride and monastral blue dye. Regional myocardial blood flows (ischaemic and nonischaemic, endocardial, epicardial) were assessed by the radioactive microsphere technique. 4. Both EXP3174 and enalaprilat induced a decrease in mean arterial blood pressure. However, non significant changes in regional myocardial blood flows, whether ischaemic or nonischaemic, were observed after administration of either the ACEI or the AT1 antagonist. 5. The size of the area at risk was similar in the three groups. By direct comparison, there were no significant differences between infarct sizes in the three groups. Furthermore, there was a close inverse relationship between infarct size and transmural mean collateral blood flow in controls, and none of the treatments altered this correlation. Thus, neither EXP3174 nor enalaprilat limited infarct size. 6. These results indicate that activation of the renin-angiotensin system does not contribute to myocyte death in this canine ischaemia/reperfusion model.

Anesthesia↗

PubMed1993

The role of NO release in the control of large and small coronary artery tone in conscious dogs.

Intravenous administration of the nitric oxide donor CAS 754 (10-100 micrograms/kg) elicited a long-lasting, highly selective, and dose-dependent increase in large epicardial coronary diameter in conscious dogs, whereas nitroglycerin (up to 0.3 micrograms/kg) induced a shorter and less selective dilation of the large conductance vessels. In contrast, acetylcholine simultaneously increased large epicardial coronary artery diameter and decreased coronary resistance, regardless of the doses administered (0.01-3 micrograms/kg). Three days after endothelium removal by limited coronary angioplasty, the vasodilator effects of acetylcholine and reactive hyperemia were suppressed, whereas those induced by CAS 754 and nitroglycerin were not significantly different from those observed before endothelium removal. These data show that the epicardial coronary vasodilator effects of both CAS 754 and nitroglycerin are endothelium-independent in vivo. Thus, the unique pharmacological profile of CAS 754 on coronary dynamics could prove to be of major importance in the treatment of angina pectoris.

Acetylcholine↗

PubMed1993

[Interaction between SR 47436, a new angiotensin II antagonist and sympathetic nervous system in pithed SHR rats].

In vivo studies have previously shown that exogenous angiotensin II (AII) reinforces sympathetic nervous system activity. Conversely, non selective inhibition of endogenous AII by angiotensin I converting enzyme inhibitors (ACEIs) results in sympathoinhibitory effects. The aim of the present study was to examine the influence of selective inhibition of endogenous AII by SR 47436, a non peptide AT1-receptor antagonist, on the sympathetic nervous system. Cardiac, systemic and regional vascular (kidney, mesentery, hindlimb) responses to selective alpha 1- and alpha 2-adrenoceptor agonists and to electrical stimulation of the spinal cord were investigated in the pithed spontaneously hypertensive rat (SHR). Male adults SHRs were orally treated by SR 47436 (10 mg/kg/day for 8 days) or by distilled water. Two hours later, they were anesthetized with pentobarbital (50 mg/kg, i.p.), pithed and artificially ventilated. Blood pressure, heart rate, cardiac output and regional (kidney, mesentery and hindlimb) blood flows (pulsed Doppler technique) were measured. Corresponding vascular resistances were calculated. Three hours after SR 47436--at the time of the drug's maximal effects--or distilled water administration, cardiac, systemic pressor and regional vasoconstrictor responses (a) to increasing i.v. doses of AII, (b) to increasing frequencies of electrical stimulation of the spinal cord, and (c) to increasing i.v. doses of cirazoline, a selective alpha 1-adrenoceptor agonist, and of UK-14,304, a selective alpha 2-adrenoceptor agonist, were investigated. AII systemic pressor, regional vasoconstrictor and tachycardic responses were completely abolished by SR 47436. SR 47436 significantly reduced the systemic pressor responses elicited by spinal cord stimulation, cirazoline and UK-14,304.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

PubMed1992

Beneficial effects of trandolapril on experimentally induced congestive heart failure in rats.

Angiotensin-converting enzyme (ACE) inhibitors have been shown to prolong life expectancy in patients with congestive heart failure. In order to determine the relative contributions of the different factors involved in this beneficial effect, we investigated in an experimental model of postinfarction cardiac insufficiency in the rat over a 9-12-month period (1) the kinetics of the development of the hemodynamic, biologic, and morphologic alterations that accompany heart failure, and (2) the kinetics of the effects of a new, long-acting ACE inhibitor, trandolapril. Following induction of infarction, systolic blood pressure, left ventricular dP/dt, and end-diastolic pressure were immediately decreased, decreased, and increased, respectively, and these modifications persisted throughout the study. Cardiac index, on the other hand, was only initially and transiently decreased. Cardiac remodeling (left ventricular dilation, myocardial hypertrophy, and fibrosis) occurred as early as 7 days after infarction and worsened throughout the study. Plasma atrial natriuretic factor (ANF) and urinary cyclic guanosine monophosphate (cGMP) were also increased. In this model, a 1-year oral treatment with trandolapril resulted in early hemodynamic and biologic beneficial effects (reductions in pre- and afterload, increase in cardiac index, and decrease in plasma ANF), and in a delayed reversal of the infarction-induced cardiac morphologic alterations. Hence, the trandolapril-induced increase in survival rate is due initially to the drug's hemodynamic effects and over the long-term to both its hemodynamic and cardiac morphologic (limitation of remodeling) effects.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1992

Systemic and regional hemodynamic effects of zabicipril in healthy volunteers.

The effects of two oral doses of zabicipril, a new angiotensin converting enzyme inhibitor, on systemic (arterial pressure, heart rate, and cardiac output) hemodynamic parameters and regional (brachial, carotid and femoral arteries' diameters and flows) hemodynamic parameters and on biologic (plasma-converting enzyme and renin activities, catecholamines, and atrial natriuretic factor) parameters were noninvasively investigated and compared with those of a placebo in a double-blind crossover study performed in six healthy male volunteers. Although it did not affect the systemic hemodynamic parameters, zabicipril induced a strong peripheral vasodilation, significantly reducing brachial, carotid, and femoral resistances and increasing the corresponding blood flows from 3 or 4 1/2 hours to 9 hours. This vasodilation affected only the arterioles, not the large arteries, and resulted in a redistribution of cardiac output toward the three regional vascular beds. Zabicipril induced an early, potent, and long-lasting converting enzyme inhibition. Furthermore, zabicipril did not affect plasma catecholamines and atrial natriuretic factor.

Analysis of Variance↗

PubMed1992

Differential effects of nitrovasodilators, K(+)-channel openers, and nicorandil on large and small coronary arteries in conscious dogs.

When administered intravenously to conscious dogs, nicorandil, nitrovasodilators (nitroglycerin and SIN-1), and the K(+)-channel opener cromakalim exhibited marked differential effects on large epicardial and small resistance coronary arteries. Nitrovasodilators markedly increased the left circumflex coronary artery diameter at doses at which coronary resistance was not significantly decreased. In contrast, both cromakalim and nicorandil dilated large and small coronary arteries in the same conditions. When coronary blood flow was held to its control value by partial inflation of a hydraulic occluder implanted around the artery, the nitroglycerin- and nicorandil-induced increases in large coronary diameter remained unchanged whereas the response to cromakalim was reduced significantly. This coronary dynamic profile indicates that both nitrovasodilators and nicorandil directly dilate large coronary vessels, whereas the effect of cromakalim on these vessels is mediated partially through a flow-dependent mechanism. This suggests that nicorandil mainly dilates large coronary arteries through its nitroglycerin-like properties, whereas its ability to dilate coronary resistance vessels depends mainly on its K(+)-channel opener-like properties.

Animals↗

PubMed1992

Flosequinan does not affect systemic and regional vascular responses to simulated orthostatic stress in healthy volunteers.

1. The effects of a single oral dose (100 mg) of flosequinan on systemic and regional (forearm, splanchnic and renal) vascular responses to simulated orthostatic stress (lower body negative pressure, LBNP) were investigated in nine healthy male volunteers, in a double-blind, placebo-controlled crossover study. 2. Forty-five minutes after its administration and before LBNP, flosequinan induced a significant decrease in total peripheral and in forearm vascular resistances without any concomitant change in arterial pressure, in heart rate and in the investigated biological parameters (plasma catecholamines, arginine vasopressin and renin activity). 3. After flosequinan and placebo, LBNP induced similar decreases in central venous pressure at all levels of LBNP (-10, -20 and -40 mm Hg) and in pulse pressure at LBNP -40 mm Hg. LBNP-induced increase in forearm vascular resistance was significantly more marked after flosequinan than after placebo at all levels of LBNP, and this was also true for splanchnic vascular resistance but at LBNP -40 mm Hg only. However, inasmuch as the basal values of these two parameters before LBNP were lower after flosequinan than after placebo, their final values after LBNP -40 mm Hg were similar. Finally, LBNP-induced changes in renal vascular resistance, glomerular filtration rate and filtration fraction as well as in plasma catecholamines, arginine vasopressin and renin activity were similar after flosequinan and placebo at all levels of LBNP. 4. Flosequinan affected neither reflex control of heart rate (phenylephrine test) nor non-specific vasoconstrictor responses (cold pressor test). (ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1992

Effects of an angiotensin converting enzyme inhibitor, ramipril, on intracranial circulation in healthy volunteers. off.

1. The effects of a single oral dose (10 mg) of ramipril on (a) systemic haemodynamics (arterial pressure, cardiac output), (b) carotid artery haemodynamics (blood flow and diameter, pulsed Doppler technique), (c) intracranial haemodynamics (middle cerebral artery mean blood velocity, transcranial Doppler technique), and (d) renin-angiotensin system (plasma converting enzyme and renin activities) have been investigated and compared with those of a placebo during the 24 h period following administration in a randomized, double-blind and cross-over study performed in six healthy volunteers. 2. Ramipril induced a strong and sustained inhibition of plasma converting enzyme activity (-96% at 4 h, -63% at 24 h) and an increase in plasma renin activity (+993% at 8 h). 3. As compared with placebo, ramipril did not significantly affect arterial blood pressure, heart rate, cardiac output and total peripheral resistance. 4. Ramipril significantly increased carotid blood flow (by 27% at 8 h) without significantly changing carotid artery diameter, indicating, given the unchanged arterial pressure, an arteriolar vasodilation in the carotid territory. 5. The middle cerebral artery mean blood flow velocity underwent spontaneous modifications during the placebo period but these changes were not affected by ramipril. This lack of influence of ramipril on intracranial haemodynamics suggests that the drug-induced arteriolar vasodilation and increase in carotid blood flow only concern the extracranial, musculo-cutaneous part of the carotid territory.

Blood Flow Velocity↗