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Biomedical subjects

C Thuillez

Publications and source records attributed to C Thuillez.

At least 55 records · Page 3Linked to original sources
PubMed1997

Altered flow-dependent vasodilatation of conduit arteries in maintenance haemodialysis.

BACKGROUND: An altered arterial nitric oxide (NO) pathway could partly explain the damage to arteries observed in haemodialyzed (HD) patients. The present study was designed to non-invasively evaluate the NO pathway of peripheral conduit arteries in HD patients. METHODS: Twelve normotensive, non-diabetic HD patients treated with erythropoietin and 12 matched healthy controls (C) were included in the study. The effect of endogenous release of NO was assessed by measuring the flow-dependent vasodilatation of the radial artery (post-ischaemic hyperaemia), and the response to exogenous NO assessed using sublingual glyceryl trinitrate administration (GTN). RESULTS: Radial artery diameter (echo-tracking), radial blood flow (RBF: Doppler) and mean arterial pressure (Finapres) were identical at baseline in HD patients and in healthy subjects. The flow-dependent vasodilatation of the radial artery was decreased in HD patients (C: 9 +/- 1% vs HD: 3 +/- 05%, P < 0.05). The decrease in radial vascular resistance (C: -44 +/- 4% vs HD: -24 +/- 2%, P < 0.05) and the increase in radial diameter (C: 31 +/- 2% vs HD: 25 +/- 2%, P < 0.05) after GTN administration were less in HD patients than in controls. The ratio between the increase in diameter after hyperaemia to the increase in diameter after GTN, was also diminished in HD patients (C: 30 +/- 3% vs HD: 13 +/- 2%, P < 0.001). CONCLUSIONS: The flow-dependent vasodilatation of peripheral conduit arteries is altered in HD patients and is associated with a slight but significant decrease in the vasodilating response to exogenous NO. These results suggest, in the absence of changes in basal radial vascular resistance and arterial diameter, more a decrease in endothelial NO bioavailability, than an increase in basal vascular tone.

Administration, Sublingual↗
PubMed1997

Pharmacokinetic-pharmacodynamic model relating spiraprilat plasma concentrations to systemic and regional hemodynamic effects in congestive heart failure.

The aim of this study was to investigate the relations between the plasma concentrations of spiraprilat (the active metabolite of the angiotensin-converting enzyme inhibitor spirapril) and its effects on plasma converting enzyme activity (PCEA), pulmonary capillary wedge pressure (PCWP), and brachial blood flow (BBF), after a single oral administration of 6 mg of spirapril in eight patients with severe congestive heart failure (CHF). Concentrations and effects were determined before and repeatedly during 48 h after drug intake. A sigmoid model was fitted to individual observations. Maximal effects, concentrations inducing half-maximal effects, and Hill coefficients were -99 +/- 2%, 3.9 +/- 1.9 ng/ml, and 2.4 +/- 0.7 for PCEA inhibition, -15 +/- 8 mm Hg, 11.8 +/- 9.2 ng/ml, and 2.6 +/- 1.3 for PCWP decrease, and 36 +/- 19 ml/min, 13.8 +/- 7.6 ng/ml, and 3.3 +/- 1.0 for BBF increase. In severe CHF, although a 14 ng/ml plasma concentration of spiraprilat may induce a 95% inhibition of PCEA, a 30 ng/ml plasma concentration is mandatory to normalize PCWP and BBF. This concentration corresponds to the peak achieved after a 6-mg oral dose of spirapril.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Response of large and small vessels to alpha and beta adrenoceptor stimulation in heart failure: effect of angiotensin converting enzyme inhibition.

The increased sympathetic drive in chronic heart failure (CHF) might provoke vascular adrenoceptor desensitization, which, together with endothelial dysfunction, could contribute to the altered vasomotor tone seen in CHF. We investigated 1) whether CHF alters the responses mediated by alpha and beta adrenoceptors in small and large peripheral arteries, and 2) the effect of angiotensin-converting enzyme (ACE) inhibition. Rats with CHF (coronary artery ligation) were treated with placebo or the ACE inhibitor lisinopril (10 mg/kg/d) starting 7 days after ligation. Responses to phenylephrine (alpha 1 agonist), salbutamol (beta 2 agonist) as well as acetylcholine (endothelium-dependent), were assessed after 3 months in isolated and pressurized segments of the abdominal aorta, the femoral and the mesenteric arteries. In animals with hemodynamic signs of CHF, neither the vasoconstrictor responses to phenylephrine nor the vasodilator response to salbutamol were affected. In contrast, the dilator response to acetylcholine of both small arteries, but not that of the aorta, was impaired. Furthermore, CHF did not modify vessel structure. While lisinopril did not modify the responses to adrenergic agonists, it normalized the response to acetylcholine. Furthermore, ACE inhibition reduced vascular media cross sectional area and collagen density. Thus, the unchanged arterial responsiveness to adrenoceptor agonists does not indicate any vascular adrenoceptor desensitization, while endothelial dependent vasodilation of small arteries is impaired in CHF. ACE inhibition does not modify the response to adrenergic stimuli, prevents endothelial dysfunction and induces both cardiac and vascular remodeling, which probably contribute to the effect ACE inhibitors have on exercise tolerance and survival.

Acetylcholine↗
PubMed1997

Gut ischemia and mesenteric synthesis of inflammatory cytokines after hemorrhagic or endotoxic shock.

The intestine plays a major role in the pathophysiology of multiorgan failure. Although the systemic inflammatory response might be induced by endotoxin released through bacterial translocation, other factors such as intestinal ischemia might be implicated. We investigated the relationship between intestinal ischemia-reperfusion and cytokine release in rat models of hemorrhagic or endotoxic shock. Plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), lactate, and endotoxin, as well as macrophage TNF-alpha and IL-6 mRNA expression, were assessed at the end of shock and resuscitation. Hemodynamic changes and lactate levels suggested the presence of intestinal ischemia in both models. Mesenteric levels of TNF-alpha and IL-6 were increased by hemorrhage and further increased after saline resuscitation. Similar results were obtained with mRNA cytokine gene expression in macrophages. Endotoxin was not detectable in the hemorrhagic group. Endotoxic shock also increased production of cytokines, which, in contrast to hemorrhage, was not further increased by resuscitation. These results suggest that intestinal ischemia-reperfusion upon hemorrhage and resuscitation may be a major trigger for cytokine gene expression in the absence of endotoxin.

Animals↗
PubMed1997

Role of nitric oxide in the regulation of the mechanical properties of peripheral conduit arteries in humans.

Whether nitric oxide (NO) contributes to the regulation of the mechanical properties of large arteries in humans is not known. We measured the effect of local administration of the inhibitor of NO synthesis N(G)-monomethyl-L-arginine (L-NMMA; 1 and 4 micromol x L[-1] x min[-1] for 5 minutes) and acetylcholine (3 and 30 nmol x L[-1] x min[-1] for 3 minutes) on radial artery diameter and wall thickness in 11 healthy volunteers using an echo-tracking system coupled to a measurement of radial blood flow (Doppler) and arterial pressure. At the highest dose, L-NMMA reduced radial blood flow but surprisingly decreased incremental elastic modulus (from 1.36+/-0.22 to 1.00+/-0.22 kPa x 10[3]; P<.05) and increased arterial compliance (from 3.20+/-0.46 to 4.07+/-0.45 m2 x kPa x 10(-8), P<.05), without affecting radial artery internal diameter, wall thickness or midwall stress, thus reflecting a decrease in vascular tone. Acetylcholine decreased incremental elastic modulus (from 1.27+/-0.08 to 0.88+/-0.07 kPa x 10[3]; P<.05) and increased arterial diameter, radial blood flow, and compliance (from 2.82+/-0.16 to 5.30+/-0.62m2 x kPa x 10[-8]; P<.05). These results demonstrate in vivo that NO is involved in the regulation of the mechanical properties of large arteries in humans. However, the effects of L-NMMA, ie, a decrease in arterial wall rigidity and an increase in arterial compliance, which occur in the absence of any changes in blood pressure or arterial geometry, suggest that inhibition of NO synthesis is associated in humans with a paradoxical isometric smooth muscle relaxation. This effect could be due to the development of compensatory vasodilating mechanisms after NO synthesis inhibition.

Acetylcholine↗
PubMed1997

[Endothelial dysfunction in cardial failure: potential mechanisms].

From the vascular point of view, cardiac failure is characterised by increased systemic resistances secondary to an increased concentration of a number of vasoconstrictor substances and also to decreased endothelium dependent vasodilatation. Endothelial dysfunction has been described both in man and in animal models, but its causes are not well understood. Such dysfunction could be due to a decrease in the production of nitric oxide, a decrease in its vasodilator effect due to an increased degradation or an increased vasoconstrictor tone. Recent data suggests an improvement or prevention of this endothelial dysfunction observed in cardiac failure by physical training and by chronic treatment with an angiotensin converting enzyme inhibitor. The improvement or preservation of endothelial function induced by exercise or ACE inhibitor could explain some of the benefits of these treatments in terms of tissue perfusion and haemodynamic conditions.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Simple high-performance liquid chromatographic method for the quantitation of 5-fluorouracil in human plasma.

A simple, rapid, specific and sensitive high-performance liquid chromatography method has been developed for quantitation of 5-fluorouracil (5-FU) in human plasma. The method involves deproteinization of a small sample volume of plasma (150 microliters) followed by HPLC on a cation-exchange resin column, Aminex HPX-87H (300 x 7.8 mm I.D.), preceded by a similar guard cartridge with UV detection at 265 nm. This method allows a good separation of 5-FU with a retention time of 24 min and a detection limit at 25 ng/ml. The calibration curve was linear from 25 to 2000 ng/ml. The coefficient of variation was < or = 4.4% for within-day reproducibility and < or = 9.5% for day-to-day reproducibility.

Antimetabolites, Antineoplastic↗
PubMed1996

Fixed-dose combination of perindopril with indapamide in spontaneously hypertensive rats: haemodynamic, biological and structural effects.

OBJECTIVE: The present study was designed to test the effects of chronic combined treatment with low doses of an angiotensin converting enzyme inhibitor (perindopril) and of the diuretic indapamide in spontaneously hypertensive rats (SHR). METHODS: Adult SHR were treated with placebo or increasing doses of the combination of the drugs (0.3, 1 and 3 mg/kg per day; ratio of doses 0.32). In a separate set of experiments, the effects of the drugs combined (1 mg/kg per day) was compared with those induced by each drug alone. RESULTS: The drug combination dose-dependently decreased systolic blood pressure and its hypotensive effect was more marked than those induced by each treatment administered alone (untreated 208 +/- 5 mmHg, indapamide 185 +/- 5 mmHg, perindopril 150 +/- 3 and the combination 123 +/- 7 mmHg). A 12-week treatment with the drug combination (1 mg/kg per day) was not accompanied by any change in diuresis or urinary excretion of Na or K. The same treatment decreased cardiac hypertrophy and collagen. At the vascular level, the drug combination decreased aortic, carotid and femoral media cross-sectional areas, as well as aortic and carotid collagen density. This latter effect was accompanied by a significant increase in carotid artery compliance assessed in vivo at constant pressure. Finally, in isolated aortae, chronic combined drug treatment was associated with an increased basal release of nitric oxide and a decrease in the hypertension-induced endothelium-dependent contractions in response to acetylcholine. CONCLUSION: These experiments suggest that chronic combined treatment with low doses of an angiotensin converting enzyme inhibitor and a diuretic such as indapamide may be of value in the treatment of hypertension.

Acetylcholine↗
PubMed1996

Systemic, pulmonary, brachial, renal and hepato-splanchnic hemodynamic effects of spirapril in severe congestive heart failure.

The effects of a single oral dose (6 mg) of the angiotensin-I converting enzyme inhibitor, spirapril, on systemic, pulmonary and regional (brachial, renal, hepato-splanchnic) hemodynamics as well as on biological parameters investigating the renin-angiotensin-aldosterone and sympathetic nervous systems were studied over a 24-hour period in eight patients with severe congestive heart failure (CHF). As compared to pretreatment values, spirapril significantly decreased mean arterial (-19%, peak effect), right atrial (-42%), mean pulmonary arterial (-38%) and pulmonary capillary wedge (-46%) pressures. Spirapril significantly decreased heart rate (-14%) and increased stroke volume index (+43%) thus resulting in a slight increase in cardiac index. All these effects were maximal between 2.5 and 4 h. Brachial artery diameter (+12%) and brachial (+41%) and renal (+36%) blood flows increased significantly whereas brachial (-41%) and renal (-36%) vascular resistances decreased significantly. All these effects were usually maximal between 1 and 2.5 h. Hepato-splanchnic hemodynamics were not drug-affected. Spirapril significantly inhibited plasma converting enzyme activity (-96% at 4 h), increased plasma renin activity (+505% at 4 h), and decreased plasma aldosterone (-46% at 24 h), norepinephrine (-31% at 24 h) and atrial natriuretic factor (-33% at 7 h). Thus, in severe CHF, acute administration of spirapril, 6 mg orally, exerts both arterial and venous vasodilating properties and improves both the systemic and regional hemodynamics and the biological status of the patients.

Aged↗
PubMed1996

The arterial wall: a new pharmacological and therapeutic target.

In recent years, two key concepts having numerous interrelationships were advanced for the understanding of various cardiovascular diseases: the "endothelial dysfunction" and the "arterial remodelling". Both endothelial dysfunction and arterial remodelling occur in various pathologies including essential hypertension, heart failure, atherosclerosis, restenosis after angioplasty, and pulmonary hypertension, and have modified the therapeutic approach by offering new pharmacological targets: specific receptors not only at the site of the vascular smooth muscle cells but also on the endothelial cells, growth factors that stimulate proliferation of smooth muscle, and receptors and enzymes of the extra-cellular matrix. Among the various substances under research, the present review will discuss angiotensin II receptor antagonists, endothelin receptor antagonists, nitrates-NO donors, potassium channel activators, and substances interfering with proteoglycans and other components of the extra-cellular matrix.

Angiotensin Receptor Antagonists↗
PubMed1996

Delayed protection of the ischemic heart--from pathophysiology to therapeutic applications.

Preconditioning the heart with brief episodes of ischemia paradoxically increases its resistance to subsequent ischemic episodes, and markedly limits infarct size. Although preconditioning is now considered as the most powerful antiischemic intervention known, its beneficial effects are short-lived since they are lost if the reperfusion period after preconditioning is extended past 2-3 h. There is, however, some evidence of a delayed phase of protection, manifest 24 h after the initial preconditioning stimulus, associated with a decrease in infarct size, a prevention of postischemic contractile dysfunction (stunning) and a reduction in endothelial injury. The delayed beneficial effects of preconditioning resemble those induced by prior heat stress, and might be related to the expression of stress proteins (heat shock proteins or HSP). Evidence for a role of HSP derives from observations showing that brief ischemia is a potent stimulus for HSP expression. Moreover, transfection of isolated cells with HSP or overexpression of HSP in transgenic mice renders the myocytes more resistant to ischemia. Once produced, HSP are believed to facilitate protein synthesis, stabilize newly formed proteins and repair denatured ones. Alternatively, delayed preconditioning may be mediated by antioxidant enzymes such as superoxide dismutase or catalase, which are also upregulated by ischemia and this could lead to a lesser production of oxygen-derived free radicals during reperfusion. Indeed, in isolated myocytes, prevention of hypoxia-induced expression of superoxide dismutase (using an antisense oligonucleotide) abolished the delayed protective effect of preconditioning. Importantly, recent in vivo evidence suggests that the delayed protection may be mediated by adenosine, through activation of A1-receptors, and by stimulation of protein kinase C. Finally, although the exact mechanisms by which preconditioning induces delayed protection are still mostly unknown, the fact that the expression of protective proteins such as HSP can be induced by many other means than ischemia suggests that it is possible to pharmacologically stimulate this expression and thus possibly mimic the endogenous protective pathway. This could lead to the development of new pharmacological interventions which induce delayed myocardial protection in clinical situations such as angioplasty, coronary bypass surgery or even in patients at high risk of infarction.

Animals↗
PubMed1996

Preconditioning prevents chronic reperfusion-induced coronary endothelial dysfunction in rats.

Experiments were designed to test whether preconditioning protects against chronic endothelial injury after ischemia and reperfusion. Coronary arteries were isolated from rats subjected to sham surgery or 20 min of ischemia followed by 1 h, 1 day, 1 wk, or 1 mo of reperfusion without or with preconditioning. The endothelium-dependent relaxations to acetylcholine (ACh; assessed in vitro) were markedly reduced after ischemia and 1 h of reperfusion (31 +/- 6 vs. 57 +/- 6% in sham; P < 0.01) and did not recover after longer durations of reperfusion (1 mo: 32 +/- 5 vs. 56 +/- 2%; P < 0.01). The impaired response to ACh was restored by preconditioning at all time points (1 h: 53 +/- 6; 1 mo: 65 +/- 4%). After 1 mo, the potency of ACh in preconditioned arteries was also increased compared with that in sham animals. Electron microscopy showed marked endothelial damage after 1 h of reperfusion and signs of regenerated endothelium after 1 mo of reperfusion. Both acute and chronic ultrastructural changes were prevented by preconditioning. Thus preconditioning, in addition to protecting myocardial cells, also protects against chronic reperfusion-induced endothelial injury, both in terms of functional and structural changes.

Acetylcholine↗
PubMed1995

Vascular and myocardial protective effects of converting enzyme inhibition in experimental heart failure.

Systemic vasoconstriction due to stimulation of the sympathetic and renin-angiotensin-aldosterone systems is a hallmark of heart failure and this is accompanied by impaired endothelium-dependent relaxations at the level of large arteries. This study investigated, in a rat model of heart failure, whether such an endothelial dysfunction also exists at the level of the resistance artery, and whether this is associated with morphologic changes, as well as the effects of chronic treatment with the angiotensin-converting enzyme inhibitor perindopril (2 mg/kg/day). After 12 months, arterial pressure, left ventricular (LV) end diastolic pressure (LVEDP), and LV dP/dt were measured in anesthetized rats. Responses to acetylcholine and nitroprusside were determined in isolated and perfused mesenteric artery segments (diameter: 280 +/- 15 microns). After fixation, vessel diameter, media cross-sectional area, and media collagen and elastin densities were measured by image analysis. After 12 months, untreated rats showed signs of heart failure, i.e., reduced LV dP/dt, and increased LVEDP, heart weight/body weight, LV cavity circumference, and myocardial collagen density. In mesenteric vessels the endothelium-dependent vasodilator response to acetylcholine was impaired, whereas the response to the nitric oxide donor nitroprusside was unaffected. Heart failure did not affect vascular morphological parameters. Perindopril decreased blood pressure and LVEDP without any modification of LV dP/dt, and prevented cardiac remodeling. At the vascular level, perindopril improved the response to acetylcholine and reduced media cross-sectional area and collagen density without affecting internal vessel diameter or elastin density. Thus, heart failure decreases endothelium-dependent vasodilator response to acetylcholine without modification of vessel structure.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1995

Nitric oxide is responsible for flow-dependent dilatation of human peripheral conduit arteries in vivo.

BACKGROUND: Experimental evidence suggests that flow-dependent dilatation of conduit arteries is mediated by nitric oxide (NO) and/or prostacyclin. The present study was designed to assess whether NO or prostacyclin also contributes to flow-dependent dilatation of conduit arteries in humans. METHODS AND RESULTS: Radial artery internal diameter (ID) was measured continuously in 16 healthy volunteers (age, 24 +/- 1 years) with a transcutaneous A-mode echo-tracking system coupled to a Doppler device for the measurement of radial blood flow. In 8 subjects, a catheter was inserted into the brachial artery for measurement of arterial pressure and infusion of the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA; 8 mumol/min for 7 minutes; infusion rate, 0.8 mL/min). Flow-dependent dilatation was evaluated before and after L-NMMA or aspirin as the response of the radial artery to an acute increase in flow (reactive hyperemia after a 3-minute cuff wrist occlusion). Under control conditions, release of the occlusion induced a marked increase in radial blood flow (from 24 +/- 3 to 73 +/- 11 mL/min; P < .01) followed by a delayed increase in radial diameter (flow-mediated dilatation; from 2.67 +/- 0.10 to 2.77 +/- 0.12 mm; P < .01) without any change in heart rate or arterial pressure. L-NMMA decreased basal forearm blood flow (from 24 +/- 3 to 13 +/- 3 mL/min; P < .05) without affecting basal radial artery diameter, heart rate, or arterial pressure, whereas aspirin (1 g PO) was without any hemodynamic effect. In the presence of L-NMMA, the peak flow response during hyperemia was not affected (76 +/- 12 mL/min), but the duration of the hyperemic response was markedly reduced, and the flow-dependent dilatation of the radial artery was abolished and converted to a vasoconstriction (from 2.62 +/- 0.11 to 2.55 +/- 0.11 mm; P < .01). In contrast, aspirin did not affect the hyperemic response nor the flow-dependent dilatation of the radial artery. CONCLUSIONS: The present investigation demonstrates that NO, but not prostacyclin, is essential for flow-mediated dilatation of large human arteries. Hence, this response can be used as a test for the L-arginine/NO pathway in clinical studies.

Adult↗
PubMed1995

In vivo evidence of an endothelin-induced vasopressor tone after inhibition of nitric oxide synthesis in rats.

BACKGROUND: Continuous production of nitric oxide (NO) from endothelial cells permanently inhibits the synthesis and the vasoconstrictor effects of endothelin. Thus, inhibition of NO synthesis might unmask a vasopressor response to endothelin. To assess whether endothelin contributes to the pressor response induced by inhibition of NO synthesis, we tested whether bosentan, a nonpeptide antagonist of ETA and ETB endothelin receptors, affected the hypertensive response induced by the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME). METHODS AND RESULTS: Anesthetized rats received increasing doses of L-NAME (0.1 to 3 mg.kg-1) in the absence or the presence of bosentan (3 mg.kg-1 IV 15 minutes before L-NAME). Bosentan itself did not affect blood pressure. L-NAME induced a dose-dependent increase in mean arterial pressure (percent increase from baseline after 3 mg.kg-1, 25 +/- 5%), and this was reduced by bosentan (13 +/- 3%; P < .05) or by the selective ETA antagonist BQ-123 (3 mg.kg-1: controls, 25 +/- 4%; BQ-123, 14 +/- 5%; P < .01). In contrast, bosentan did not affect the pressor response to phenylephrine (1 to 100 micrograms.kg-1). The response to L-NAME (3 mg.kg-1) was also reduced by bosentan in ganglion-blocked (chlorisondamine 2.5 mg.kg-1: controls, 89 +/- 10%; bosentan, 45 +/- 7%) or pithed rats (controls, 165 +/- 9%; bosentan, 85 +/- 12%; P < .01). Bosentan also inhibited the pressor response to another inhibitor of NO synthesis, NG-nitro L-arginine (3 mg.kg-1) in normal (controls, 24 +/- 5%; bosentan, 10 +/- 3%; P < .01) or ganglion-blocked (controls, 86 +/- 13%; bosentan, 25 +/- 8%; P < .01) rats. Finally, L-NAME induced a modest increase in plasma levels of endothelin-1 (controls, 26.8 +/- 4.1 pg.mL-1; L-NAME, 38.5 +/- 3.3 pg.mL-1; P < .05). CONCLUSIONS: These experiments demonstrate that inhibition of NO synthesis unmasks a tonic pressor influence of endothelin, suggesting that this peptide could play a major role in pathophysiological situations associated with an impaired formation of NO.

Animals↗
PubMed1995

Prevention of endothelial dysfunction in small and large arteries in a model of chronic heart failure. Effect of angiotensin converting enzyme inhibition.

Chronic heart failure (CHF) impairs endothelium-dependent vasodilatation of large conductance arteries. We investigated whether a similar reduction also occurs in small arteries, and whether such a reduction can be prevented by the angiotensin converting enzyme inhibitor perindopril (P) in a rat model of CHF (left coronary artery ligation). After 1 month treatment with placebo or P (2 mg/kg/day), rats were anesthetized and arterial pressure, left ventricular end-diastolic pressure, and central venous pressure were measured with a micromanometer. Segments of aorta and mesenteric artery (mean diameter, 281 +/- 8 microns) were then isolated, cannulated, and perfused at constant pressure using an arteriograph. Responses to increasing concentrations of acetylcholine (Ach), nitroprusside, and to 10(-4) mol/L NG-nitro-L-arginine methyl ester (L-NAME) were studied after preconstriction by phenylephrine. Heart failure resulted in a decrease in systolic and diastolic pressures, an increase in left ventricular end-diastolic and central venous pressures, and a significant depression of Ach-induced dilatation of the mesenteric artery (maximal dilatation, from 90 +/- 4% to 63 +/- 4%, P < .05) but not of the aorta (from 56 +/- 8% to 45 +/- 5%, NS) without any modification in the endothelium-independent vasodilatation induced by nitroprusside. In the group treated by the angiotensin converting enzyme (ACE) inhibitor perindopril, systolic and diastolic pressures were slightly decreased, whereas left ventricular end diastolic, central venous pressures, and the endothelium-dependent vasodilating response to Ach were normalized. Responses to L-NAME were not affected by CHF or perindopril. Perindopril also decreased hypertrophy, as evidenced by a significantly lower heart weight in treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗