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V Richard

Publications and source records attributed to V Richard.

At least 91 records · Page 5Linked to original sources
PubMed1995

Role of basal and stimulated release of nitric oxide in the regulation of radial artery caliber in humans.

Although it is well established that nitric oxide contributes to the regulation of resistance arterial tone in humans, its role at the level of large arteries is less clear. Therefore, we assessed in healthy volunteers the effect of local administration of the inhibitor of nitric oxide synthesis NG-monomethyl-L-arginine (L-NMMA) on basal radial artery diameter (transcutaneous A-mode echotracking) and radial blood flow (Doppler) as well as on the radial response to acetylcholine and the nitric oxide donor sodium nitroprusside. A catheter was inserted into the brachial artery for measurement of arterial pressure and infusion of L-NMMA (2, 4 and 8 mumol/min for 5 minutes, n = 11), acetylcholine (3, 30, 300 and 900 nmol/min for 3 minutes, n = 8), and nitroprusside (2.5, 5, 10, and 20 nmol/min for 3 minutes, n = 6). None of the treatments affected arterial blood pressure or heart rate. L-NMMA dose-dependently decreased radial blood flow (from 31 +/- 6 to 17 +/- 3 10(-3) L/min after 8 mumol/min, P < .01) but did not affect radial artery diameter (from 2.93 +/- 0.11 to 2.90 +/- 0.14 mm). Acetylcholine dose-dependently increased radial blood flow (154 +/- 43% after 900 nmol/min) and radial artery diameter (16 +/- 4%), and both effects were markedly reduced after L-NMMA (increase in radial blood flow and radial artery diameter: 22 +/- 20% and 3 +/- 2%, respectively; both P < .01 versus controls). Nitroprusside also dose-dependently increased radial artery diameter (14 +/- 4% after 20 nmol/min) but only moderately affected radial blood flow (47 +/- 21%).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1995

Activity of combinations of dapsone, rifampin, minocycline, clarithromycin, and sparfloxacin against M. leprae-infected mice.

In these studies we evaluated the activity of low levels of five antimicrobials against Mycobacterium leprae-infected mice when administered singly and in all possible two- and three-drug combinations. Antibiotics studied were: dapsone (D) 0.0001% in the diet, rifampin (R) 20 mg/kg by gavage once monthly, minocycline (M) 0.004% in the diet, clarithromycin (C) 0.001% in the diet, and sparfloxacin (S) 5 mg/kg by gavage five times weekly. Singly each agent was found bacteriostatic (D + R) or partially bactericidal (M, C, and S) but not fully bactericidal. All 10 two-drug regimens were found at least bacteriostatic, 2 being "partially bactericidal" and 4 being "fully bactericidal." Of the 10 three-drug regimens, 9 were found "fully bactericidal" and the other "partially bactericidal." We conclude that combinations of antibiotics active against M. leprae are generally additive in combination.

Animals↗
PubMed1995

[Role of nitric oxide in the regulation of the mechanical properties of peripheral muscular arteries in man].

Although several experiments have demonstrated the existence of a basal NO-dependent vasodilatory tone at the arteriolar level, the contribution of NO to the mechanical properties of large arteries has not been investigated in humans. To evaluate the effect of NO-synthase inhibition on these mechanical properties, radial artery internal diameter (d, mm) and wall thickness (h, mm) were measured continuously in 11 healthy volunteers (age: 24 +/- 1 years), using an A-mode echo-tracking system coupled to a Doppler device for the measurement of radial blood flow (RBF, ml/min). A catheter was inserted in the brachial artery for measurement of arterial pressure (AP, mmHg), and infusion of the inhibitor of NO synthesis NG-monomethyl L-arginine (L-NMMA: 4 mumol/min for 5 min, infusion rate 0.8 ml/min). Arterial compliance C, 10(-3) mm2/mmHg), distensibility (D, 10(-3)/mmHg), mid-wall stress (sigma, 10(5) dynes/mm2) and incremental modulus (Ei, 10(7) dynes/mm2) were calculated before and after L-NMMA. After L-NMMA, RBF decreased from 31 +/- 6 to 23 +/- 4 (p < 0.05), radial vascular resistance increased from 2.70 +/- 0.35 to 3.77 +/- 0.55 (p < 0.05), without changes in AP or heart rate. Table shows mechanical parameters, assessed at fixed AP (80 mmHg) (*: p < 0.05 vs baseline): [table: see text] Thus, the L-NMMA-induced decrease in radial arterial wall stiffness (Ei) without changes in arterial diameter or stress demonstrates that NO-synthase inhibition induces an isometric relaxation of vascular muscle cells, which explains the increase of arterial compliance at constant mid-wall stress. These results demonstrate that NO contributes to the regulation of peripheral muscular arterial mechanics in humans. At the level of large arteries, the isometric relaxation observed after NO-synthase inhibition is probably the consequence of compensatory vasodilator mechanisms.

Adult↗
PubMed1995

[Demonstration of a vasopressor role of endogenous endothelin after inhibition of nitric oxide synthesis in rats].

Although it is clear that vascular endothelial cells synthesize and release endothelin (ET), the contribution of this vasconstrictor peptide to the regulation of vascular tone appears limited in normal conditions. One possibility to explain this moderate effect is that continuous production of nitric oxide (NO) may permanently inhibit the release and the vasoconstrictor effects of ET. In these conditions, inhibition of NO synthesis might unmask a vasopressor response to ET. Thus, we tested whether bosentan (3 mg/kg i.v.), a non-peptide antagonist of ETA and ETB receptors, or BQ-123 (3 mg/kg), an antagonist of ETA receptors, affected the hypertensive response induced by the NO synthase inhibitors NG-nitro-L-arginine methyl ester (L-NAME 3 mg/kg) or NG-nitro L-arginine (3 mg/kg) in anesthetized, normotensive rats. Bosentan or BQ-123 did not affect blood pressure. L-NAME significantly increased mean arterial pressure (% increase from baseline: 25 +/- 5%), and this was reduced by bosentan (13 +/- 3%; p < 0.05) or by BQ-123 (14 +/- 5%; p < 0.01). In contrast, bosentan did not affect the pressor response to phenylephrine. The response to L-NAME (3 mg/kg) was also reduced by bosentan in ganglion-blocked (chlorisondamine: 2.5 mg/kg; controls 89 +/- 10; bosentan: 45 +/- 7%) or pithed rats (controls: 165 +/- 9; bosentan 85 +/- 12%; p < 0.01). Bosentan also inhibited the pressor response to NG-nitro L-arginine (3 mg/kg-1) in normal (controls 24 +/- 5, bosentan 10 +/- 3%; p < 0.01) or ganglion-blocked rats (controls 86 +/- 13; bosentan 25 +/- 8; p < 0.01). Finally, L-NAME induced a modest increase in plasma levels of ET-1 (controls: 26.8 +/- 4.1; L-NAME: 38.5 +/- 3.3 pg/ml; p < 0.05). Thus, acute inhibition of NO synthesis unmasks a tonic vasopressor influence of ET.

Animals↗
PubMed1994

Is guanidino succinate a precursor for nitric oxide synthesis in rat vascular tissue?

Although L-Arginine (L-Arg) is considered the physiological precursor of nitric oxide (NO) synthesis in endothelial cells, recent experiments suggested that another guanidino derivative, guanidino succinate, may also serve as a major source of NO in this tissue. We tested this hypothesis in rat aortas, using two experimental situations in which L-Arg had previously shown significant activity, i.e., the ability to counteract contractile responses to the L-Arg analogue NG-nitro-L-arginine methyl ester (L-NAME) and the relaxation observed after prolonged incubation in physiologic buffer. Rat aortic rings, with or without endothelium, were suspended in organ chambers for recording of isometric tension and were contracted by phenylephrine (PE). After a brief incubation period (0.5 h), L-Arg, D-Arg, or guanidino succinate induced only minor relaxations in rings with or without endothelium. In the presence of L-NAME, L-Arg (but not the D-enantiomer), induced concentration-dependent relaxations of rings with endothelium (relaxation to L-Arg 10(-3) M 52 +/- 13%), reflecting a reversal by L-Arg of the L-NAME-induced potentiation of the contraction to PE. In contrast to L-Arg, guanidino succinate was less effective in the presence than in the absence of L-NAME (relaxation to guanidino succinate 10(-3) M before L-NAME 37 +/- 8% and after L-NAME 14 +/- 3%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Role of endogenous endothelin in myocardial and coronary endothelial injury after ischaemia and reperfusion in rats: studies with bosentan, a mixed ETA-ETB antagonist.

1. Previous studies suggested that endothelin-1 (ET-1) may play a role in myocardial ischaemia and reperfusion. This study was designed to test the effect of a new nonpeptide antagonist of endothelin ETA and ETB receptors, bosentan, on myocardial infarct size, ventricular arrhythmias, and coronary endothelial dysfunction after ischaemia and reperfusion. 2. Anaesthetized male Wistar rats were subjected to 20 min ischaemia (left coronary artery occlusion) followed by 1 h (for the evaluation of coronary endothelial dysfunction) or 2 h (for the evaluation of infarct size) reperfusion, or 5 min ischaemia followed by 15 min reperfusion (for the evaluation of reperfusion arrhythmias). Vascular studies were performed on 1.5-2 mm coronary segments (internal diameter 250-300 microns) removed distal to the site of occlusion and mounted in wire myographs for isometric tension recording. Area at risk and infarct size were determined by Indian ink injection and triphenyl tetrazolium staining, using computerized analysis of enlarged sections after colour video acquisition. 3. Bosentan, administered at a dose which virtually abolished the pressor response to big ET-1 (3 mg kg-1, i.v. before ischaemia) did not affect heart rate, arterial pressure or the rate pressure product before ischaemia, during ischaemia and during reperfusion. Bosentan did not affect the incidence of reperfusion-induced ventricular fibrillation (controls: 86%, n = 14; bosentan: 93%, n = 15), and did not modify infarct size (% of area at risk: controls: 63 +/- 4, n = 10; bosentan: 60 +/- 6, n = 8). Ischaemia followed by reperfusion markedly reduced the endothelium-dependent relaxations to acetylcholine(maximal response: sham: 59 +/- 4%, n = 9; ischaemia-reperfusion: 26+/- 6%, n = 8; P<0.01), characteristic of reperfusion-induced endothelial dysfunction, and this dysfunction was not prevented by bosentan (maximal response to acetylcholine: 25 +/-5%, n = 9; P<0.01 vs sham; P = NS vs ischaemia/reperfusion).4. These experiments suggest that endogenous endothelin does not contribute to myocyte or coronary endothelial injury in this rat model of ischaemia and reperfusion.

Animals↗
PubMed1994

Ischemic preconditioning protects against coronary endothelial dysfunction induced by ischemia and reperfusion.

BACKGROUND: Repetitive, brief periods of ischemia and reperfusion ("preconditioning") increase the resistance of myocardial tissue to subsequent prolonged ischemic episodes and limit infarct size. We investigated whether preconditioning also protects against coronary endothelial dysfunction induced by ischemia and reperfusion. METHODS AND RESULTS: Experiments were performed in four groups of rats (n = 8 in each group): group 1 rats underwent sham surgery, group 2 rats were subjected to 20 minutes of left coronary artery occlusion without reperfusion, group 3 rats underwent 20 minutes of occlusion followed by 1 hour of reperfusion, and group 4 rats (preconditioning group) underwent the same protocol as group 3 rats, preceded by three cycles of 5 minutes of ischemia and 5 minutes of reperfusion. At the end of the experiments, coronary segments (internal diameter, 250 to 300 microns) were removed distal to the occlusion site and mounted in wire myographs for isometric tension recording. Relaxations induced by increasing concentrations of acetylcholine, the calcium ionophore A23187, or the nitric oxide (NO) donor SIN-1 were determined in arteries precontracted by serotonin. Basal NO release was estimated by measuring contractions to NG-nitro L-arginine methyl ester (L-NAME). In addition, we determined the effect of preconditioning on infarct size in two additional groups that were subjected to the same protocols as those of groups 3 and 4. In those animals, area at risk (India ink injection) and infarct size (triphenyltetrazolium stain) were determined by computerized analysis of enlarged sections after video acquisition. Preconditioning markedly limited infarct size (percent of area at risk: controls, 57 +/- 2; preconditioning, 2.2 +/- 0.6; P < .01). Ischemia (without or with reperfusion) or preconditioning did not affect the coronary responses to L-NAME, serotonin, A23187, or SIN-1. Ischemia without reperfusion did not modify the relaxations to acetylcholine (maximal relaxation: sham, 58 +/- 4%; ischemia, 56 +/- 7%; P = NS). In contrast, ischemia followed by reperfusion markedly impaired the response to acetylcholine (26 +/- 6%; P < .01 versus sham). This impaired response was restored by preconditioning (maximal relaxation: 59 +/- 9%; P = NS versus sham; P < .01 versus ischemia/reperfusion). CONCLUSIONS: In addition to protecting myocardial cells, preconditioning also protects coronary endothelial cells against ischemia/reperfusion injury.

Acetylcholine↗
PubMed1994

Endothelins. A potential target for pharmacological intervention in diseases of the elderly.

The existence of vasoconstrictive factors originating from the endothelium was confirmed by the description of endothelin, a 21-amino-acid peptide derived from a series of precursors, preproendothelin and a 38-amino-acid big endothelin. Three isoforms of endothelin, endothelin-1, -2 and -3, and 3 receptors (ETA, ETB and ETC) have been described and cloned. The cellular mode of action of endothelin seems to involve the modulation of intracellular calcium (through inositol trisphosphate, diacylglycerol and phospholipase C) and activation of calcium channels. The effects of endothelin are predominantly on the cardiovascular system. Its major effect is vasoconstriction, both systemic and pulmonary, with additional positive chronotropic and inotropic effects on the heart. It has also been implicated in homeostatic regulation of kidney microcirculation, and has powerful mitogenic effects on fibroblasts and smooth muscle cells. Many additional effects have been described on the endocrine system and on other systems. However, the clinical relevance of such effects is uncertain. Increased plasma endothelin levels have been reported in many diseases, but as yet it is not certain whether they are a cause or a consequence of the pathology. Pathologies most probably related to endothelin dysfunction are the vasospastic diseases, especially vasospasm after subarachnoid haemorrhage. Endothelin could be implicated to a lesser measure in diseases typical of the elderly population, such as hypertension or atherosclerosis. Drugs are being developed which act on endothelin metabolism, the most promising of which appear to be the inhibitors of endothelin converting enzyme and endothelin receptor antagonists. Some already existing drugs, such as calcium channel blockers or angiotensin converting enzyme inhibitors, probably act at least in part by interfering with endothelin metabolism or effects.

Aged↗
PubMed1994

Hydralazine dilates large epicardial coronary arteries in conscious dogs through an endothelium-independent mechanism.

In chronically instrumented conscious dogs, hydralazine (30-300 micrograms/kg) and nitroglycerin (NTG 0.03-10 micrograms/kg) dose-dependently dilated large epicardial coronary arteries. Simultaneously, hydralazine also dose-dependently dilated small coronary arteries, whereas a similar effect was observed only after NTG > 0.3 microgram/kg. When large coronary arteries were deendothelialized by a balloon angioplasty catheter, dilation of large coronary arteries in response to acetylcholine (ACh 0.3 microgram/kg) and to reactive hyperemia was reduced by 87 and 95%, respectively. In contrast, vasodilation of large coronary arteries induced by hydralazine and NTG was only minimally and similarly affected (-19% for both drugs). These findings demonstrate that in vivo hydralazine-induced dilation of large coronary arteries is endothelium independent.

Angioplasty, Balloon↗
PubMed1994

[Changes in the mechanical properties of the arterial wall evaluated in vivo in the spontaneously hypertensive rat].

Recent experiments demonstrated increased isobaric arterial compliance and distensibility in hypertensive patients, which could be explained by a decrease in arterial wall stress, when assessed at constant pressure. We investigated the effect of hypertension on the mechanical properties of the carotid arterial wall, and especially wall stress, assessed in vivo in spontaneously hypertensive rats (SHR). Right carotid artery internal diameter (ID) and wall thickness (WT) were continuously monitored in 30 week old anesthetized SHR (n = 8) or their normotensive controls (WKY, n = 7), using a high resolution (1 micron) transcutaneous A-mode echo-tracking system (NIUS 2), coupled to a measurement of left carotid arterial pressure (micromanometer). Mean arterial pressure was 123 +/- 6 in WKY and 202 +/- 2 mmHg in SHR (p < 0.01). Mechanical parameters were calculated at mean pressure from ID and WT-pressure curves (*: p < 0.01 vs WKY). There was no difference between the groups for ID (WKY: 1.13 +/- 0.07; SHR: 1.20 +/- 0.06 mm, NS) and mid-wall stress (WKY: 10.5 +/- 1.2; SHR: 10.5 +/- 0.7 10(5) dynes/cm2, NS) while WT was increased in SHR (WKY: 105 +/- 8; SHR: 191 +/- 16 microns, p < 0.01). In SHR, incremental modulus (wall rigidity) was increased (WKY: 0.86 +/- 0.09; SHR: 1.96 +/- 0.25 10(7) dynes/cm2, p < 0.01) while distensibility (WKY: 1.77 +/- 0.16; SHR: 0.54 +/- 0.06 10(-3) mmHg-1, p < 0.01) and compliance (WKY: 1.84 +/- 0.30; SHR: 0.61 +/- 0.07 10(-3) mm2/mmHg, p < 0.01) were decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

[Role of nitric oxide in flow-dependent vasodilation of human peripheral arteries in vivo].

Experiments performed in isolated arteries or in animals suggested that flow-dependent dilatation of conduit arteries is mediated through the release of endothelium-derived nitric oxide (NO). The present study was designed to assess whether NO also contributes to flow-dependent dilatation of conduit arteries in humans. Radial artery internal diameter was measured in 8 healthy volunteers (age 22 +/- 1 years), using a transcutaneous A-mode echo-tracking system, coupled to a Doppler device for the measurement of radial blood flow. A catheter was inserted in the brachial artery for measurement of arterial pressure and infusion of the L-arginine analogue NG-monomethyl L-arginine (L-NMMA (8 mumol/min for 7 min, infusion rate 0.8 ml/min). Flow-dependent dilatation was evaluated before and after L-NMMA as the response of the radial artery to an acute increase in flow (reactive hyperemia after a 3 min distal cuff occlusion). Release of the occlusion induced a significant increase in radial blood flow (from 27 +/- 4 to 82 +/- 13 ml/min; p < 0.01) followed by a delayed increase in radial diameter (flow-mediated dilatation; from 2.77 +/- 0.13 to 2.85 +/- 0.13 min; p < 0.01), without any change in heart rate or arterial pressure. L-NMMA induced a significant decrease in basal forearm blood flow (from 27 +/- 4 to 14 +/- 2 ml/min; p < 0.05), without affecting basal radial artery diameter, heart rate or arterial pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Human deoxyhaemoglobin-2,3-diphosphoglycerate complex low-salt structure at 2.5 A resolution.

The haemoglobin-2,3-diphosphoglycerate complex structure has been solved at 2.5 A resolution using crystals grown from low-salt solutions. The results show some important differences with the precedent haemoglobin-2,3-diphosphoglycerate high-salt structure solved by Arnone. First, we observe a loss of symmetry in the binding site, secondly both of the lysine residues 82 beta interact with 2,3-diphosphoglycerate at the same time, each making two contacts. This level of interaction is in agreement with the functional behaviour of natural haemoglobin mutants with mutations at the 2,3-diphosphoglycerate binding site.

2,3-Diphosphoglycerate↗
PubMed1993

Ischaemic preconditioning is not mediated by oxygen derived free radicals in rats.

OBJECTIVE: Although several studies have shown that ischaemic preconditioning greatly limits myocardial infarct size in the rat, the mechanisms of the beneficial effect of preconditioning in this species are not known. Experiments in dogs and rabbits have suggested that this effect could be related in part to the production of oxygen derived free radicals, as free radical scavengers partially prevent the limitation of infarct size induced by preconditioning. This study was designed to assess the contribution of oxygen derived free radicals in the infarct size limiting effects of preconditioning in rats, using the cell diffusible free radical scavenger N-2-mercaptopropionyl glycine (MPG). METHODS: Open chest rats underwent 20 minutes of coronary occlusion followed by one hour of reperfusion. Preconditioning was elicited by three cycles of five minutes ischaemia and five minutes reperfusion. MPG (20 mg.kg-1) was infused for 60 minutes starting 30 minutes before preconditioning. Control hearts (with or without MPG) were treated identically but without ischaemic preconditioning. Area at risk and infarct size were determined by India ink injection and triphenyltetrazolium chloride stain, with computerised analysis of enlarged sections after colour video acquisition. RESULTS: During preconditioning, reperfusion after the first episode of ischaemia was associated with a high occurrence of severe ventricular arrhythmias, and this was reduced by MPG. Preconditioning, however, reduced arrhythmias and mortality during subsequent episodes of ischaemia and reperfusion. In the absence of MPG, preconditioning greatly limited infarct size (from (mean (SEM)) 59.8(3.9)% to 1.2(0.6)% of the area at risk; p < 0.01). MPG alone did not affect infarct size (60.5(6.1)%), and did not modify the infarct size limiting effect of preconditioning (infarct size: preconditioning 1.2(0.6)%; preconditioning + MPG 2.9(1.2)%. CONCLUSIONS: Preconditioning greatly reduced infarct size, and this was not affected by MPG. These experiments suggest that production of oxygen derived free radicals does not contribute to preconditioning in the rat heart.

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

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

[Mechanical adaptation of muscular arteries to acute increase of blood pressure in man. Contribution of the measurement of arterial wall thickness].

Although it was usually admitted that hypertension is associated with a reduction in conduit artery compliance and distensibility, recent experiments using newly developed high precision echo-tracking devices allowing simultaneous, non-invasive measurements of blood pressure and arterial diameter have suggested that compliance and distensibility, when calculated at equal transmural pressure, could indeed be maintained, or even increased, in hypertensive subjects. Such a maintained arterial compliance could be explained best by a decrease in wall stress despite the increase in arterial blood pressure, through either an increase in wall thickness or a decrease in arterial wall elastic modulus. Thus, the goal of the present study was to assess the role of the changes in these determinants of vessel compliance in the arterial response to an acute increase in arterial pressure in 7 healthy volunteers. Arterial pressure (AP, Finapress) as well as right radial artery internal diameter and wall thickness (Echo-Tracking, NIUS 2, Asulab) were measured continuously before and after a 2 min cold pressor test (CPT). The following parameters were then calculated at fixed (105 mmHg) pressure from the pressure/diameter curve: compliance (mm2/mmHg) and distensibility (mmHg-1) mid-wall stress (dynes/cm2) and incremental elastic modulus (dynes/cm2). During CPT, mean AP increased (from 83 +/- 4 to 106 +/- 8 mmHg; p < 0.01), compliance distensibility; and mean internal diameter (mm) decreased, mean wall thickness (mm) increased, whereas wall stress and elastic modulus remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗