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Biomedical subjects

J F Giudicelli

Publications and source records attributed to J F Giudicelli.

At least 127 records · Page 7Linked to original sources
PubMed1991

[Flow-dependent vasodilation. Pharmacology and physiopathology].

The phenomenon of flow-dependent vasodilatation is characterised by the variations of vascular tone to changes in regional blood flow. Initially considered to be a purely myogenic reaction of a vessel to a change in blood flow in the microcirculation, it is now generally accepted that "flow-dependent" vasodilatation is closely related to the modulating properties of the vascular endothelium. Local chemical or mechanical destruction of the vascular endothelium abolishes any vasomotor response in that particular region to increased blood flow in that vessel (for example during a hyperemic response or after injection of papaverine), whereas the response to a substance directly relaxing the smooth muscle of the large arteries (such as nitroglycerine) remains unchanged. Bioassay methods have shown that the fundamental mechanism of flow dependence is the liberation of one or more relaxing factors (EDRF) from endothelial cells sensitive to variations in shear stress which accompany all changes in regional blood flow. From the pharmacological point of view, flow-dependent vasodilatation enables identification of several types of vasodilator drugs depending on whether the relaxation of vascular smooth muscle which follows their administration remains the same or not in the absence of concomitant changes in regional blood flow. The vasodilatation caused by calcium antagonists and potassium agonists is largely related to the phenomenon of flow-dependency whilst that induced by nitroglycerin is totally independent. Finally, from the physiopathological view-point, the clinical studies published in this domain show that blood pressure has little influence on flow-dependent vasodilation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Angiotensin converting enzyme inhibition. Systemic and regional hemodynamics in rats and humans.

The systemic and regional hemodynamic effects of angiotensin I converting enzyme inhibitors (ACEIs) have been investigated using different experimental methods (pulsed Doppler, radioactive microspheres), either in rats (normotensive NT or genetically hypertensive SHRs) or in humans (healthy volunteers or patients with congestive heart failure CHF). All ACEIs decreased systemic vascular resistance but the profile of their peripheral vasodilating properties was heterogeneous. ACEI-induced vasodilation primarily affected the kidney in rats and in humans and this effect was accompanied by a strong and consistent increase in renal blood flow. This occurred even at non-hypotensive doses in SHRs and CHF patients and resulted in a favorable redistribution of cardiac output towards the kidney. In the muscular vascular bed, ACEIs also decreased local vascular resistance in rats and in humans, whether normotensive or hypertensive. In humans, this vasodilation affected both the arterioles and the large conductance vessels, more markedly in CHF patients than in normotensive subjects. Muscular blood flow was increased and a favorable redistribution of cardiac output towards the muscle occurred. Cerebral blood flow in SHRs and carotid blood flow in humans were augmented, whereas hepatosplanchnic blood flow was increased in rats but not modified in humans. There was no major difference between the regional vasodilating profiles of the different ACEIs, but captopril was somewhat less active at the muscular level. In conclusion, ACEI-induced regional vasodilation is heterogeneous, preferentially affecting the kidney and the muscle. In the latter, both arterioles and large conductance vessels are dilated.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1990

Cardiac and hemodynamic effects of S(-)- and (R(+)-DPI 201-106 and of racemic DPI 201-106 in conscious dogs.

The cardiac and hemodynamic effects of (+/-)-DPI 201-106 (0.6 mg/kg), S(-)-DPI (0.3 mg/kg), R(+)-DPI (0.3 mg/kg), and their vehicle were compared in chronically implanted conscious dogs. (+/-)-DPI and S(-)-DPI induced qualitatively and quantitatively similar effects, increasing LV dP/dt, cardiac output and stroke volume and reducing total peripheral resistance. In contrast, R(+)-DPI decreased only stroke volume. It is concluded that (a) the positive inotropic effects of (+/-)-DPI in vivo are caused by its S(-) enantiomer, and (b) the peripheral vasodilating effects of (+/-)-DPI may not be linked to the drug's calcium antagonist properties.

Animals↗
PubMed1990

Cardiovascular and biological effects of K+ channel openers, a class of drugs with vasorelaxant and cardioprotective properties.

Several new chemical entities (RP 52891, cromakalim and its derivatives) are potent and specific openers of vascular K+ channels. This mechanism is also shared, at least partially, by drugs such as minoxidil, diazoxide, pinacidil and nicorandil. The opening of plasmalemma K+ channels produces loss of cytosolic K+. This effect results in cellular hyperpolarization and functional vasorelaxation. In normotensive or hypertensive rats, K+ channel activators decrease aortic blood pressure (by producing a directly mediated fall in systemic vascular resistance) and reflexly increase heart rate. The former effect is not modified by specific blockers of classical vascular receptors but it is completely antagonized by the hypoglycemic sulphonylurea, glibenclamide, an established blocker of ATP-regulated K+ channels. K+ channel openers produce selective coronary vasodilatation and afford functional and biochemical protection to the ischemic myocardium. This salutary effect is mediated via cardiac K+ channel modulation and may result from an improved myocardial oxygen balance in the ischemic region. K+ channel openers increase plasma renin activity in animals as well as in man. However, only diazoxide, but not cromakalim or RP 52891, lowers plasma insulin concentration. The dose of glibenclamide entirely blocking the latter effect is over 50-fold smaller than that antagonizing the hypotensive and hyper-reninemic responses to diazoxide. In conclusion, K+ channel activators are potent vasorelaxant and cardioprotective agents possessing an original mechanism of action which is the opening of plasmalemma ATP-regulated K+ channels. Their clinical use as antihypertensive agents may be accompanied by undesirable effects (characteristic of peripheral vasodilators) which are likely to be attenuated or avoided by controlled release formulations. However, inasmuch as low doses of K+ channel openers may be sufficient to produce selective coronary artery dilatation and cardioprotection, these compounds could be of particular value in treating patients with coronary artery disease efficaciously and possibly without adverse cardiovascular effects.

Animals↗
PubMed1990

Systemic and regional hemodynamic effects of perindopril in congestive heart failure.

The acute systemic and regional hemodynamic responses to a single oral dose (4 mg) of the angiotensin converting enzyme inhibitor perindopril were investigated in 10 patients with severe congestive heart failure. Perindopril produced significant and long-lasting decreases in systemic vascular resistance (-18%), right atrial pressure (-60%), and mean pulmonary capillary wedge pressure (-28%), whereas it significantly increased cardiac index (+ 12%). Brachial (+ 130%, pulsed Doppler technique) and renal (+ 34%) blood flows were also significantly increased whereas hepatic blood flow remained unchanged. Brachial flow/cardiac output and renal flow/cardiac output ratios increased significantly from 0.8 to 1.6 and from 13.2 to 16.5, respectively. The maximal decreases in forearm and renal (but not in systemic) vascular resistances were correlated with the basal plasma norepinephrine concentrations but not plasma epinephrine concentrations or plasma renin activity. We conclude that in severe heart failure (a) perindopril considerably improves systemic hemodynamics and exerts an inhomogeneous vasodilating effect, resulting in a redistribution of flows toward the forearm and renal territories, (b) norepinephrine is a major determinant of the arteriolar tone in these two vascular beds, and (c) the pulsed Doppler is a particularly suitable method to non-invasively detect and assess hemodynamic improvements in heart failure patients.

Administration, Oral↗
PubMed1990

Hemodynamic and cardiac effects of spiraprilat in normal and sodium depleted conscious dogs.

The cardiac and hemodynamic effects of 3 doses (0.1, 0.3 and 1 mg/kg, iv) of spiraprilat, the diacid active metabolite of the new angiotensin I converting enzyme inhibitor spirapril, have been investigated and compared to those of saline in chronically implanted conscious dogs at rest. Under a normal sodium diet, spiraprilat, 1 mg/kg, induced significant (at least P less than 0.05) decreases in mean arterial pressure (MAP, -11%), total peripheral resistance (TPR, -21%), left ventricular end diastolic pressure (LVEDP, -15%) and increases in heart rate (HR, +12%) and cardiac output (CO, +16%) whereas dP/dtmax remained unchanged. Spiraprilat-induced tachycardia was not modified by propranolol pre-treatment but was abolished by previous administration of the propranolol-N-methylatropine combination. Spiraprilat, 0.1 mg/kg, did not affect any parameter, but spiraprilat, 0.3 mg/kg, showed intermediate effects. Finally, sodium depletion strongly potentiated spiraprilat effects on MAP, TPR, LVEDP, HR and CO. We conclude that: a), in conscious dogs under normal sodium diet, spiraprilat reduces TPR and MAP through peripheral vasodilating properties; b), spiraprilat-induced tachycardia is mainly related to parasympathetic tone withdrawal, possibly in relation with high and low pressure baroreceptors deactivation; and c), sodium depletion considerably potentiates spiraprilat cardiac and hemodynamic effects.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1990

Systemic and regional haemodynamic interactions between K+ channel openers and the sympathetic nervous system in the pithed SHR.

1. The interactions between two K+ channel openers, cromakalim and SR 44866 (infused i.v. at equihypotensive doses), and the sympathetic nervous system at the systemic and regional (mesentery, kidney, hindlimb) vascular levels were investigated in the pithed spontaneously hypertensive rat (SHR) by use of the pulsed Doppler technique. 2. The two K+ channel openers did not affect postsynaptic alpha 1- but slightly reduced postsynaptic alpha 2-adrenoceptor mediated systemic pressor and regional vasoconstrictor responses. 3. Both drugs significantly decreased the systemic pressor and regional vasoconstrictor responses elicited by spinal cord stimulation. These sympathoinhibitory effects were not homogeneously distributed among the different vascular beds, the decreasing rank order being: mesentery greater than kidney greater than hindlimb. Simultaneously, the spinal cord stimulation-induced tachycardia remained unaffected. 4. After treatment with K+ channel openers, restoration of initial blood pressure and vascular tone values by infusion of prostaglandin F2 alpha (PGF2 alpha) and vasopressin respectively did not affect and abolished the sympathoinhibitory effects of cromakalim and SR 44866. 5. We conclude that in SHRs the two K+ channel openers that we investigated exert similar sympathohibitory effects which affect some vascular beds more than others. These effects are not dependent upon the arterial blood pressure level and are most likely prejunctionally located.

Animals↗
PubMed1990

[The humeral artery and clinical pharmacology].

Regional haemodynamic parameters such as blood flow, brachial artery diameter and forearm resistances may be measured or calculated non-invasively by pulsed Doppler techniques, and, in the absence of blood pressure changes, provide a method of observing and quantifying the vasomotor tone of small or large arteries. This type of study therefore allows characterisation of the vascular effects of drugs whether they be vasodilators or substances with a preferential mode of action on the myocardium. These effects can be situated with respect to the central hemodynamics in order to determine the presence of phenomena of regional redistribution of cardiac output, the regional vascular changes observed after taking a meal or in cardiac failure, with and without treatment; this should lead to a better understanding of the mode of action of drugs used in cardiovascular disease and also of the underlying physiopathological mechanisms.

Arm↗
PubMed1990

Effects of cromakalim and pinacidil on large epicardial and small coronary arteries in conscious dogs.

The effects of i.v. bolus administration of cromakalim (1-10 micrograms/kg) and pinacidil (3-100 micrograms/kg) on large (circumflex artery) and small coronary arteries and on systemic hemodynamics were investigated in chronically instrumented conscious dogs and compared to those of nitroglycerin (0.03-10 micrograms/kg). Nitroglycerin, up to 0.3 micrograms/kg, selectively increased circumflex artery diameter (CxAD) without simultaneously affecting any other cardiac or systemic hemodynamic parameter. In contrast, cromakalim and pinacidil at all doses and nitroglycerin at doses higher than 0.3 micrograms/kg simultaneously and dose-dependently increased CxAD, coronary blood flow and heart rate and decreased coronary vascular resistance and aortic pressure. Cromakalim was approximately 8- to 9.5-fold more potent than pinacidil in increasing CxAD. Vasodilation of large and small coronary vessels and hypotension induced by cromakalim and pinacidil were not affected by prior combined beta adrenergic and muscarinic receptors blockade but drug-induced tachycardia was abolished. When circumflex artery blood flow was maintained constant, the increases in CxAD induced by cromakalim (10 micrograms/kg), pinacidil (30 micrograms/kg) and nitroglycerin (10 micrograms/kg) were reduced by 68 +/- 7, 54 +/- 9 and 1 +/- 1%, respectively. Thus, whereas nitroglycerin preferentially and flow-independently dilates large coronary arteries, cromakalim and pinacidil dilate both large and small coronary arteries and this effect is not dependent upon the simultaneous beta adrenoceptors-mediated rise in myocardial metabolic demand. Finally, two mechanisms at least, direct vasodilation and flow dependency, are involved in the cromakalim- and pinacidil-induced increase in CxAD.

Animals↗
PubMed1990

[Modeling of the relation between plasma concentration of the active metabolite of perindopril and inhibition of the activity of plasma converting enzyme in healthy volunteers].

UNLABELLED: The purpose of this study was to investigate the relationship between plasma concentration (Cp) of perindoprilat (P), the active metabolite of perindopril, and plasma converting enzyme activity (CEA) after a single oral administration of perindopril. CEA and Cp were investigated before, and, 1, 2, 3, 4, 6, 8, 10, 24 and 48 hours after a random administration of a placebo or 4, 8, 16 mg perindopril in a double-blind and crossover study performed in 6 healthy male volunteers. Effect on CEA was expressed as the percentage of inhibition of pretreatment value (CEA0): CEI = 100 (CEA0 = CEA)/CEA0. The CEI-Cp relationship was non linear and displayed an hysteresis loop. Following Sheiner et al. (Clin Pharmacol Ther, 1979; 25: 358-71), we used an effect compartment in which drug dissipation is governed by a first-order rate constant keo. Concentration of P in the effect compartment (Ce) was related to CEI by the Hill equation CEI = 100 Emax Cen/(EC50n + Cen), where Emax (expressed as a percentage) is the theoretical maximum effect, EC50 the Ce which produces 50 p. 100 of Emax, and n the Hill coefficient. Pharmacodynamic parameters were estimated by the non parametric approach proposed by Unadkat et al. (Clin Pharmacol Ther, 1986; 40: 86-93). The Hill equation was fitted to the data for 3 different values of n: 1, 2, and 3. RESULTS: for all the 3 doses, the best curve fitting was achieved for n = 1 or 2. We obtained keo = 0.60 +/- 0.30 h-1 (mean +/- s.d.), Emax = 90 +/- 10 p. 100, EC50 = 1.30 +/- 0.95 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

Cardiac and hemodynamic profile of the new cardiotonic agent, DPI 201-106, in the conscious dog.

The cardiac and hemodynamic effects of increasing doses (0.1-3 mg/kg i.v.) of the novel cardiotonic agent, DPI 201-106 (DPI), were investigated over a 60 min period in conscious dogs chronically instrumented for the measurement of arterial pressure, heart rate, left ventricular pressure (LVP), LV (+) dP/dtmax and cardiac output. LV (+) dP/dtmax, cardiac output and stroke volume were significantly increased by DPI whereas the total peripheral resistance was significantly decreased. These effects were dose-dependent in intensity and in duration. The mean arterial pressure and heart rate remained unaffected, except by the 3 mg/kg dose, which increased them slightly. Autonomic blockade with hexamethonium, atropine and propranolol did not alter the positive inotropic properties of DPI but unmasked its intrinsic bradycardic effect. At equipotent positive inotropic doses, DPI (0.3 mg/kg), milrinone (40 micrograms/kg) and dobutamine (5 micrograms/kg per min) induced similar increases in cardiac output and similar decreases in total peripheral resistance, but only dobutamine and milrinone accelerated the heart rate, whereas ouabain (17.5 micrograms/kg) induced a strong rise in the total peripheral resistance and markedly lowered the heart rate and cardiac output. After coadministration of DPI and ouabain, LV (+) dP/dtmax was further increased whereas the ouabain-induced bradycardia, the rise in the total peripheral resistance and the decrease in cardiac output were reinforced, halved and unaltered, respectively. We conclude that (a) DPI exhibits potent and direct positive inotropic properties, associated with a peripheral vasodilating action, and almost no positive chronotropic effects, and (b) coadministration of DPI and ouabain results in synergistic positive inotropic effects.

Animals↗
PubMed1989

Differential systemic and regional hemodynamic profiles of four angiotensin-I converting-enzyme inhibitors in the rat.

Angiotensin-converting enzyme (ACE) inhibitors decrease blood pressure by reducing systemic vascular resistance. That the peripheral vasodilating properties of ACE inhibitors might not be homogeneously distributed in all vascular beds and might differ from one drug to another has been investigated in the normotensive rat by the pulsed Doppler technique using the active components of four different ACE inhibitors: captopril, enalapril, perindopril, and ramipril. Systemic (cardiac output and blood pressure) and regional (kidney, mesentery, hindquarter) hemodynamic responses to saline or to cumulative bolus injections (0.01-1 mg/kg) of captopril, enalaprilat, perindoprilat, or ramiprilat were continuously monitored. The effects of successive bolus injections (0.3-300 ng/kg) of angiotensinII were also investigated. The four ACE inhibitors produced an almost complete blockade of plasma angiotensin-II converting-enzyme activity (83%, 100%, 100%, and 100%, respectively), induced dose-dependent decreases in mean blood pressure, did not significantly affect cardiac output, and reduced total peripheral and mesenteric vascular resistances to the same extent. Hindlimb vascular resistance was identically decreased, but to a lower extent than total peripheral resistance by enalaprilat, perindoprilat, and ramiprilat, whereas it was increased by captopril at low doses only. Renal resistance was markedly decreased by the four drugs, and especially by captopril. The decreasing rank order for ACE-inhibitor-induced vasodilation is exactly the same (renal greater than total peripheral = mesenteric greater than hindlimb vascular resistances) as that of angiotensin-H-induced regional vasoconstriction, indicating that the vasodilator properties of ACE inhibitors are mainly due to angiotensin-II vasomotor tone suppression. None of the investigated compounds significantly affected mesenteric and hindlimb blood flows, except captopril, which lowered the latter significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1989

Comparison of the efficacy of propranolol and amiodarone in suppressing ventricular arrhythmias following myocardial infarction.

The purpose of this prospective randomized trial was to compare the efficacy of propranolol and amiodarone in suppressing ventricular arrhythmias during the first 6 months following myocardial infarction (MI). 97 patients were treated with either amiodarone (n = 48) or propranolol (n = 49) starting on the 9th day following MI. Holter monitoring was carried out on four occasions: on D7, D21, D90 and D180. There was no statistical difference in the incidence of 'major' arrhythmias (an average of at least 10 ventricular premature complexes (VPCs) h-1, multiform or paired VPCs or runs) between the two groups on D7. A significant difference in favour of amiodarone became apparent at D180 (P = 0.04). Patients were also classified according to whether treatment failed or was successful. 'Success' was recorded when arrhythmias remained minor or became minor (less than 10 uniform VPCs h-1) and 'failure' when arrhythmias remained major or became major, or when patients were withdrawn because of side-effects, or lost to follow-up. The difference remained in favour of amiodarone (P = 0.03 at D21; P = 0.05 at D90; P = 0.06 at D180). Evaluation of the percentage reduction in the number of VPCs at D21, D90 or D180 compared with D7 showed superiority of amiodarone at D90 (P less than 0.01) and D180 (P less than 0.04). In this study, the overall effect of amiodarone on ventricular arrhythmias following MI was shown to be superior to that of propranolol.

Aged↗
PubMed1989

Functional antagonism between PK 11195, a peripheral benzodiazepine receptor antagonist, and nicardipine at the vascular level in healthy subjects: a peripheral hemodynamic study.

The effects of PK 11195, a peripheral benzodiazepine receptor antagonist (200 mg orally), of nicardipine (20 mg orally), of their combination, and of a placebo on brachial and carotid arteries, diameters, and flows were determined and compared over a period of 8 h after drug intake during a double-blind and cross-over study performed on six healthy volunteers. Simultaneously, plasma concentrations of both drugs were measured. PK 11195 significantly increased carotid and more markedly brachial arteries, flows (20 and 39%, respectively), and diameters (4 and 7%, respectively) and decreased forearm vascular resistance. Thus, PK 11195 preferentially affected the resistance vascular beds where it dilated both large arteries and arterioles. The intensity and duration of the peripheral vasodilating effects of PK 11195 were similar to those of nicardipine. Simultaneous administration of PK 11195 and nicardipine abolished almost all the peripheral vasodilating effects of both drugs. This finding, which was not related to a pharmacokinetic interaction between PK 11195 and nicardipine, demonstrates that in humans a functional antagonism develops between these two drugs at the vascular level.

Adult↗
PubMed1989

Relationship between mixed venous oxygen saturation and cardiac index in patients with chronic congestive heart failure.

The use of mixed venous oxygen saturation (SvO2) in patients with chronic congestive heart failure (CHF) has been advocated to analyze the action of therapy on cardiac index (CI). To evaluate the relationship between CI and SvO2, ten CHF patients (mean age 65 years) were studied before and one, two, three, four (T4), six, eight and 24 hours after oral administration of an angiotensin converting enzyme (ACE) inhibitor (perindopril, 4 mg). At T4, a 12 percent increase in CI (p less than 0.01) was associated with a 16 percent decrease in arteriovenous oxygen difference (p less than 0.01), a 13 percent increase in mixed venous oxygen pressure (PvO2) (p less than 0.01), and a 9 percent increase in SvO2 (p less than 0.05) with no significant change in arterial oxygen pressure. There was no correlation between CI and SvO2 (r = 0.22) and between CI and PvO2 (r = 0.23). Individual analyses were performed and patients were divided into two groups based on CI versus SvO2 r value; group 1, n = 6, r greater than 0.65 (0.65-0.90), group 2, n = 4, r less than 0.65 (0.14-0.20). The lack of correlation in group 2 was due to a drug-dependent increase in oxygen consumption (VO2) +18 percent vs -3 percent in group 1 (p less than 0.05) associated with a lack of increase in PvO2 +3 percent vs +14 percent in group 1 (p less than 0.05) despite a similar increase in oxygen availability +19 percent versus +16 percent. It was concluded that (1) a correlation between CI and SvO2 is not found in every patient with CHF; (2) the lack of correlation in four out of our ten patients was due to an associated and significant increase in CI and VO2 in group 2; (3) group 2 patients probably had an important oxygen debt before treatment; (4) SvO2 cannot be used instead of CI to determine the hemodynamic consequences of the use of cardiovascular drugs.

Administration, Oral↗
PubMed1989

Ketanserin: systemic and regional hemodynamic characterization of its serotonergic and alpha-adrenergic receptor blocking effects in the pithed SHR.

The interactions between ketanserin and serotonin (5-HT)- and alpha-adrenoceptor agonists (alpha 1, cirazoline; alpha 2, UK-14,304)-induced systemic and regional (kidney, hindquarter, mesentery) hemodynamic responses were investigated in the pithed spontaneously hypertensive rat (SHR) using the pulsed Doppler technique. Serotonin, cirazoline, and UK-14,304 dose dependently increased systemic blood pressure and local vascular resistances. However, the regional vasoconstrictor profiles of serotonin (hindquarter greater than kidney greater than mesentery) and cirazoline (kidney greater than hindquarter greater than mesentery) were found not to be homogeneous. Ketanserin antagonized the systemic and regional hemodynamic effects of serotonin and cirazoline but not of UK-14,304. The ketanserin-serotonin antagonism was noncompetitive and occurred at doses (3-30 micrograms/kg) 100-fold lower than those (300-3,000 micrograms/kg) at which a presumably competitive antagonism developed between ketanserin and cirazoline. Furthermore, ketanserin antagonized serotonin, as well as cirazoline, homogeneously in all vascular beds. These data together with those previously obtained with ketanserin in the intact SHR (reduction in blood pressure starting at 300 micrograms/kg, heterogeneous regional vasodilator profile: hindquarter greater than kidney greater than mesentery) indicate that (a) the antihypertensive effects of ketanserin in the SHR can principally, although perhaps not exclusively, be ascribed to the drug's alpha 1-adrenoceptor blocking properties, and (b) the heterogeneous regional vasodilator profile of the drug is not due solely to the homogeneous antagonism that it exhibits versus the regional vasoconstrictor effects of alpha 1-adrenoceptors activation.

Adrenergic alpha-Antagonists↗
PubMed1989

[Non-invasive regional and cardiac output determination in healthy volunteers. Predictive value].

The effects of nifedipine (20 mg), propranolol (80 mg), the nifedipine (20 mg) + propranolol (80 mg) combination and a placebo on cardiac [heart rate (HR), cardiac output (CO, Doppler determination)] and systemic [mean arterial pressure (MAP), systemic vascular resistance (SVR)] and regional hemodynamic [brachial blood flow (BBF) and arterial diameter (BAD) (pulsed Doppler), forearm vascular resistance (FVR)] parameters were investigated during the 3 hours following their random administration in a double blind and cross over study performed in 6 healthy subjects. At their peak effects, (a) nifedipine decreased SVR (-17 p. 100, p less than 0.01), increased HR (+ 12p. 100, p less than 0.001) and CO (+ 18 p. 100, p less than 0.001), did not change MAP and increased BBF (+31 p. 100, p less than 0.001) with a vasodilating effect which affected both large and small arteries; (b) propranolol decreased HR (-14 p. 100, p less than 0.05) and CO (-25 p. 100, p less than 0.01), increased SVR (+25 p. 100, p less than 0.01), did not change MAP and decreased BBF (-28 p. 100, p less than 0.05) with a vasoconstrictor effect which affected both large and small arteries; (c) in the nifedipine-propranolol combination, nifedipine neutralized propranolol-induced systemic and regional vasoconstrictor effects while propranolol antagonized nifedipine-induced increases in HR and CO. Thus, the favorable synergistic effects of the nifedipine-propranolol combination in hypertensive patients could be demonstrated in healthy subjects inasmuch as MAP was decreased and peripheral vascular blood flows were preserved.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗