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Biomedical subjects

J F Giudicelli

Publications and source records attributed to J F Giudicelli.

At least 109 records · Page 6Linked to original sources
PubMed1992

Long-term treatment with trandolapril opposes cardiac remodeling and prolongs survival after myocardial infarction in rats.

Long-term treatment with angiotensin I converting enzyme inhibitors (ACEIs) prolongs survival in rats developing congestive heart failure after myocardial infarction (MI). In this experimental model, we investigated at regular intervals the effects of a 1-year oral treatment with trandolapril, a new ACEI, on (a) survival rate and duration and (b) hemodynamic, biological, and cardiac and vascular histomorphological parameters. Control MI rats and sham-operated trandolapril-treated and control rats were simultaneously studied. In MI rats, trandolapril significantly increased the survival rate and duration, increasing the life expectancy by approximately 6 months. It also significantly decreased the arterial blood pressure and increased diuresis. These effects occurred as soon as the treatment was started and persisted throughout the study. Trandolapril significantly limited the development of myocardial hypertrophy, decreasing the heart weight and left ventricular hypertrophic area and increasing the left ventricular myocyte nuclear density, but these effects, starting after 3-6 months, were delayed compared to the hemodynamic ones. Finally, trandolapril limited the development of myocardial (both subendocardial and subepicardial) and aortic fibrosis. It is concluded that the early pre- and afterload effects of trandolapril are initially responsible for its beneficial action on survival, whereas later the drug's antihypertrophic and antifibrotic properties together with persistent hemodynamic effects account for the prolonged survival improvement.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Use of ultrasonic and microsphere techniques to evaluate regional aspects of vasodilator therapy in myocardial ischaemia, arterial hypertension and heart failure.

PURPOSE: To review regional aspects of vasodilator therapy in myocardial ischemia, arterial hypertension and heart failure. DATA IDENTIFICATION: Results were obtained from experiments (1) performed either in experimental animals or in human volunteers or patients; (2) using either ultrasonic or microsphere techniques; (3) on the effects of different drug classes, including angiotensin converting enzyme inhibitors, calcium antagonists, potassium channel openers and nitrates; and (4) on the arterial and arteriolar vasodilating effects of different drug classes. CONCLUSIONS: The regional vasodilator effects, both arteriolar and arterial, of the major classes of drugs used in the treatment of coronary insufficiency, arterial hypertension and cardiac failure appear to be heterogenous. This heterogeneity is seen with a given drug in different vascular beds; within a class of drugs in a single vascular region; and between the regional vasodilator profiles of different classes of drugs. From the clinical point of view, the consequences of this heterogeneous vasodilation may be either positive (increase in flow, favourable redistribution of flow) or negative (steal phenomenon, opening of shunts).

Animals↗
PubMed1992

Potassium channel openers dilate large epicardial coronary arteries in conscious dogs by an indirect, endothelium-dependent mechanism.

Cromakalim and pinacidil, two potassium channel openers, dilate both large and small coronary arteries in conscious dogs. Because flow-mediated dilation of large arteries is endothelium-dependent, the consequences of in vivo endothelium removal (balloon denudation) on the response of large epicardial coronary arteries to cromakalim (10 micrograms/kg) and pinacidil (30 micrograms/kg) were investigated in six dogs chronically instrumented for the measurement of arterial pressure, left circumflex coronary artery diameter and coronary blood flow. Endothelium removal abolished the dilation of large coronary arteries induced by acetylcholine (endothelium-dependent dilation) and reactive hyperemia (flow-mediated dilation), but only slightly reduced (-18%) that induced by nitroglycerin. Before endothelium removal, both cromakalim and pinacidil induced a significant decrease in coronary resistance (-71 +/- 2 and -63 +/- 2%, respectively) and a significant increase in coronary diameter (8.5 +/- 1.3 and 6.7 +/- 0.9%). After endothelium removal, the decreases in coronary resistance were unaffected, but the increases in coronary diameter were reduced by 93 and 98% as compared to predenudation responses with cromakalim and pinacidil, respectively (both P < .01). In contrast, in vitro studies performed in isolated large epicardial coronary arteries obtained from five additional dogs showed that cromakalim evoked relaxations that were not affected by prior in vivo endothelium removal. Thus, despite the presence of potassium channels in isolated denuded large coronary arteries, our data demonstrate that cromakalim- and pinacidil-induced dilation of large arteries in vivo is an indirect, flow-mediated effect which is entirely endothelium-dependent.

Acetylcholine↗
PubMed1992

[Systemic and coronary hemodynamic effects of inhibition of nitrogen monoxide synthesis in conscious dogs].

Fourteen mongrel dogs were chronically instrumented on the circumflex coronary artery for measurement of coronary diameter (CD; Piezoelectric crystals) and coronary blood flow (CBF: Doppler flow probe). Coronary resistance (CR) was calculated as mean arterial blood pressure (MAP)/CBF. Systemic and coronary effects of three intravenous doses of NG-nitro-L-arginine (L-NAME: 0.1; 0.3; 1 mg/kg) were recorded (n = 5). Systemic and coronary effects of two vasodilators, acetylcholine (ACH) (endothelium-dependent: 0.3 micrograms/kg) and nitroglycerin (NTG) (endothelium-independent: 1 microgram/kg) were compared before and after L-NAME (1 mg/kg) (n = 6). Finally, the effects of L-NAME (1 mg/kg) were compared one week before and three days after denudation (balloon catheter) of the circumflex coronary artery (2 cm up and downstream from the crystals attachment site). All experiments were performed in conscious dogs. L-NAME induced a dose-dependent constriction of large epicardial coronary arteries [-1.5 +/- 0.5% from 3.1 +/- 0.3 mm, p < 0.05; -4.0 +/- 0.7% from 3.2 mm, p < 0.001; -5.3 +/- 1.2% from 3.0 mm, p < 0.01; respectively]. L-NAME 0.3 and 1 mg/kg induced a significant increase in MAP [+12.5 +/- 3.0% from 90 +/- 4 mmHg, p < 0.01; +11.3 +/- 3.5% from 96 +/- 7 mmHg, p < 0.05; respectively] and CR [+18.0 +/- 8.3% from 9.8 +/- 3.0 mmHg/cm.s, p < 0.01; +18.7 +/- 8.2% from 10.4 +/- 3.0 mmHg/cm.s, p < 0.01; respectively] with a significant bradycardia, but CBF was not modified. Effects of ACH were unchanged after L-NAME.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1992

[Differential action of nitrate derivatives and arterial vasodilators on coronary circulation. An experimental approach and therapeutic consequences].

The discovery of endothelial regulatory properties in the modulation of the vascular response to pharmacological agents and its fundamental role in the phenomenon of flow-dependence has enabled the demonstration of the mode of action of coronary vasodilators on the large epicardial vessels where most coronary spasm occurs. Nitrate derivatives are remarkably selective in their effects on the large vessels which dilate in an endothelial-independent manner, which makes them very effective in the prevention and treatment of coronary spasm occurring, for example, during angioplasty. On the other hand, arterial vasodilators, like calcium antagonists or potassium agonists have decreased vasodilatory effects on these conductance vessels in the presence of endothelial lesions as their action is partially or entirely endothelium-dependent. By their additive coronary vasodilator effects, the association of these two groups of vasodilators provides greater therapeutic efficacy in the prevention of angina whatever its cause.

Animals↗
PubMed1992

Baroreflex control of regional vascular resistances during simulated orthostatism.

Orthostatic stress or moderate hypovolemia was simulated in 10 healthy volunteers by the lower body negative pressure technique (LBNP at -10, -20 and -40 mm Hg). LBNP induced a progressive and parallel decrease in central venous pressure and cardiac output but mean arterial pressure remained unchanged regardless of the LBNP level. Heart rate and pulse pressure were only significantly increased and decreased at LBNP -40 mm Hg, respectively, indicating that cardiopulmonary baroreflexes were selectively deactivated up to LBNP -20 mm Hg, whereas both cardiopulmonary and arterial baroreflexes were deactivated at LBNP -40 mm Hg. The LBNP-induced increase in total peripheral resistance was heterogeneously distributed within the body. Forearm vasoconstriction occurred at low levels of LBNP and was exclusively related to an increase in sympathetic tone. Splanchnic vasoconstriction also occurred at low levels of LBNP, but was related to activation in sympathetic and renin-angiotensin systems. Renal vasoconstriction occurred mainly at high levels of LBNP (-40 mm Hg), but glomerular filtration rate and filtration fraction increased at low levels of LBNP (-10 mm Hg). Thus, if renal vascular resistance is not of major importance for the control of blood pressure during orthostatism or moderate hypovolemia, neurohumoral mechanisms triggered through deactivation of cardiopulmonary receptors play a key role in the maintenance of intrarenal homeostasis associated with reduction in cardiac filling pressure.

Adult↗
PubMed1991

[Potassium channel activators. Perspectives in the treatment of arterial hypertension].

Potassium channel activators (PCAs) open the membrane potassium channels, thus increasing the cell potassium efflux. This results in hyperpolarization of the cell membrane, the main result of which is a reduction of the penetration of calcium into cells. The resulting decrease of intracellular Ca++ produces relaxation of the smooth muscle fibres, notably in blood vessels. In animals, PCAs reduce total peripheral resistance and lower blood pressure. These vasodilator and hypotensive effects are accompanied by reflex tachycardia and stimulation of the renin-angiotensin system and they are antagonized by glibenclamide, an antagonist of ATP-dependent potassium channels. Very recent experimental data have shown that in the ischaemic myocardium PCAs tend to improve the balance between oxygen supply and demand and to exert a cardioprotective effect. Up to now, the only use of PCAs has been in arterial hypertension, and the only drugs used are pinacidil, minoxidil and diazoxide. Unfortunately, the PCAs that are available at present are rather poorly tolerated, which limits their development in this particular field. However, their combination with beta-blockers and/or diuretics reduces the incidence of their side-effects and improves their effectiveness. A synergistic effect between PCAs and angiotensin-converting enzyme inhibitors is probable.

Antihypertensive Agents↗
PubMed1991

Non invasive study of systemic and regional haemodynamic and cardiac effects of a new calcium antagonist, SR 33557, in healthy volunteers.

The systemic and regional haemodynamic and cardiac effects of two oral doses (100 and 300 mg) of a new sulphone-indolizine calcium antagonist SR 33,557 (SR) and a placebo were non invasively investigated in a double-blind, cross-over study in 6 healthy male volunteers. Arterial pressure, heart rate, cardiac output, brachial and carotid artery diameters and flows and PR and QT intervals were studied. Stroke volume, total peripheral and forearm vascular resistance, regional cardiac output distribution indices and corrected QT intervals were calculated. SR did not produce any significant modification in systemic haemodynamics, although arterial pressure and cardiac output tended to decrease slightly after 300 mg. In contrast, at the regional level, ST produced strong vasodilatation and significantly increased brachial and carotid blood flow. SR-induced vasodilation affected only the arterioles, as shown by a significant decrease in forearm vascular resistance, but not the large arteries, as shown by lack of change in the brachial and carotid artery diameters. SR-induced vasodilation preferentially affected the brachial rather than the carotid vascular bed, resulting in a redistribution of cardiac output towards the musculo-cutaneous territories. SR caused a marked and long-lasting decrease in heart rate, but it did not affect the auriculo-ventricular conduction time.

Adult↗
PubMed1991

Hemodynamic effects of hydroxocobalamin in conscious dogs.

Hydroxocobalamin has been shown to be a rapid and powerful antidote in acute cyanide poisoning and to prevent cyanide poisoning during sodium nitroprusside administration. However, its hemodynamic effects remain unknown. The authors therefore investigated the effects in chronically instrumented conscious dogs (n = 8) that were randomly given hydroxocobalamin (20, 70, and 140 mg.kg-1) or saline. Determination of peak cobalt plasma concentrations showed that 20 and 70 mg.kg-1 hydroxocobalamin correspond to "therapeutic doses," whereas 140 mg.kg-1 corresponds to a supratherapeutic dose. Hydroxocobalamin did not modify heart rate, mean arterial pressure, left ventricular (LV) end-diastolic pressure, and PR and QT intervals, regardless of the dose administered. The largest dose (140 mg.kg-1) induced a decrease in the maximum increase of LV pressure (-7 +/- 3%; P less than 0.05), maximum aortic blood flow acceleration (-17 +/- 5%; P less than 0.05), and cardiac output (-19 +/- 6%; P less than 0.05), whereas systemic resistance increased (+41 +/- 9%; P less than 0.05). In six other dogs, local administration of hydroxocobalamin (0.5, 1.5, and 5.0 mg.kg-1.min-1) confirmed that, in large doses, this drug has direct vasoconstrictor properties affecting both conductance (decrease in iliac artery diameter: -2.5 +/- 0.8%) and resistance (decrease in iliac artery blood flow: -19.5 +/- 3.4%) vessels. Thus, hydroxocobalamin should be a safe cyanide antidote, considering the lack of hemodynamic effects within the therapeutic range of doses.

Animals↗
PubMed1991

Hemodynamic and morphological effects of quinapril during genetic hypertension development.

The relative contributions of the hemodynamic and morphological (vascular and cardiac) modifications induced by long-term administration of an angiotensin I-converting enzyme inhibitor, quinapril, to the drug's long-lasting preventive effects vis-à-vis genetic hypertension development (GHD) have been investigated in young spontaneously hypertensive rats (SHRs). Two groups of SHRs were given quinapril (10 mg/kg/day) or distilled water from 5 to 20 weeks of age. The drug was then stopped, but observations continued for another 7 weeks. At selected times systemic and regional hemodynamic parameters as well as cardiac and vascular morphological effects were investigated. During the treatment period, quinapril partially opposed GHD and limited the early rise in total peripheral and regional vascular resistances observed in control animals. Quinapril's partial preventive effect vis-à-vis GHD persisted, but faded after treatment withdrawal. From a morphological point of view, quinapril strongly opposed aortic wall hypertrophy as evidenced by significant reductions in media thickness and wall to lumen ratio and by a significant increase in aortic nuclear density. Quinapril also limited vascular fibrosis development. At the cardiac level, quinapril reduced heart weight to body weight ratio and opposed myocardial hypertrophy and cardiac collagen synthesis. All these vascular and cardiac morphological changes were delayed (starting after 9-15 weeks of treatment) as compared to quinapril's hemodynamic effects. Finally, the drug's vascular and cardiac antihypertrophic properties persisted after treatment withdrawal. In conclusion, our data indicate that the early systemic and regional hemodynamic effects of quinapril initiate its antihypertensive action, but the drug-induced delayed and prolonged vascular morphological changes later take over and may be partly responsible for quinapril's residual blood pressure lowering effects after treatment withdrawal.

Animals↗
PubMed1991

Coronary effects of a combined beta adrenoceptor blocking and calcium antagonist therapy in running dogs.

The effects of YM-16151 (1 mg/kg, i.v.), a combined beta 1-adrenoceptor blocking and calcium antagonist drug, on large (circumflex artery) and small coronary arteries and on systemic hemodynamics were investigated in chronically instrumented conscious dogs at rest and during treadmill exercise. These effects were compared to those in the same animals of nicardipine (0.1 mg/kg, i.v.), atenolol (1 mg/kg, i.v.) and their combination (at the same doses). Circumflex artery diameter (CxAD) and coronary blood flow increased and coronary vascular resistance (CVR) decreased during control exercise under saline. YM-16151 and the nicardipine-atenolol combination similarly dilated large and small coronary arteries at rest, but dilation of large conductance vessels was abolished during exercise, while CVR decreased further. Both YM-16151 and the nicardipine-atenolol combination only slightly increased the rate-pressure product at rest, but strongly opposed its exercise-induced rise. Nicardipine maximally increased CxAD, decreased CVR, and enhanced the rate-pressure product at rest and during exercise. Conversely, atenolol decreased CxAD and the rate-pressure product and increased CVR at rest, but large coronary arteries remained constricted during exercise despite the concomitant dilation of small resistance vessels. Thus, in the coronary vascular bed of conscious dogs, YM-16151 really behaves as a hybrid drug, combining beta 1-adrenoceptor blocking and calcium antagonist properties, both at rest and during exercise. As a result, YM-16151 increases oxygen supply at rest and decreases oxygen demand during exercise. Finally, this study emphasizes the major role of beta 1-adrenoceptors in the mediation of exercise-induced dilation of large coronary arteries.

Adrenergic beta-Antagonists↗
PubMed1991

Arterial vasodilating profile and biological effects of pinacidil in healthy volunteers.

1. The effects of pinacidil (25 mg, sustained release formulation) a) on systemic (arterial pressure, cardiac output) and regional (brachial and carotid arteries' diameters and flows) haemodynamics (pulsed Doppler techniques), b) on sympathetic (plasma noradrenaline) and renin-angiotensin (plasma renin activity) systems, and c) on atrial natriuretic factor have been investigated and compared with those of a placebo during the 12 h period following oral administration in a randomized, double-blind and cross-over study performed in six healthy volunteers. Simultaneously, the plasma levels of pinacidil and of its active metabolite, pinacidil N-oxide, were determined. 2. As compared with placebo, pinacidil decreased systemic vascular resistance and arterial blood pressure but cardiac output was not modified. 3. Pinacidil significantly increased brachial and carotid arteries' diameters (by 7 and 8% respectively) and flows (by 60 and 17% respectively) and decreased forearm vascular resistance (by 43%). Thus, pinacidil dilates both large and small arteries, increases large vessels' compliance and redistributes blood flow towards the muscular vascular bed. These effects peaked at 4 h and their duration at the brachial level was 8 h. 4. Pinacidil administration resulted in a stimulation of both sympathetic (increases in heart rate and plasma noradrenaline) and renin-angiotensin systems, and induced a transient increase in atrial natriuretic factor. 5. The duration of pinacidil haemodynamic effects at the brachial level is consistent with the pharmacokinetic data which show that pinacidil and pinacidil N-oxide plasma levels almost plateaued between 3 and 8, and 2 and 8 h respectively after oral administration of the sustained release formulation used.

Adult↗
PubMed1991

Alpha-adrenoceptor subtypes and regional myocardial blood flow distribution during coronary occlusion in dogs.

The involvement of postsynaptic alpha-adrenoceptors in the distribution of regional myocardial blood flows (RMBFs, microsphere technique) within the left ventricle has been investigated during intermittent coronary artery occlusion in open-chest anesthetized dogs. Two types of RMBFs distribution were assessed: (1) between endocardial (endo) and epicardial (epi) layers (endo/epi ratio) and (2) between nonischemic (NIZ) and ischemic zones (IZ) (IZ/NIZ ratio). Equipressor does of selective alpha 1-(cirazoline after rauwolscine) and alpha 2-(UK-14,304 after prazosin) adrenoceptor agonists were infused in dogs previously submitted to ganglionic and muscarinic blockade. In a control group, aortic pressure was mechanically raised by aortic stenosis to levels similar to those reached with both alpha-adrenoceptor agonists. Cirazoline and aortic stenosis increased RMBFs in IZ and NIZ but did not alter the calculated coronary resistance in NIZ and did not affect endo/epi and IZ/NIZ ratios. In contrast, UK-14,304 preferentially augmented coronary resistance in NIZ, increased IZ/NIZ ratio (both P less than 0.05) but did not affect endo/epi ratio in IZ and NIZ. Thus, we conclude that if transmural distribution of RMBFs (endo/epi ratio) is not preferentially controlled by any alpha-adrenoceptor subtype, postsynaptic alpha 2-adrenoceptors are of importance during coronary occlusion in promoting a favorable redistribution of RMBFs from NIZ towards IZ by inducing a selective NIZ coronary vasoconstriction (ie a "reverse coronary steal").

Adrenergic alpha-Agonists↗
PubMed1991

Compared peripheral vascular responses to intravenous and intra-arterial administrations of positive inotropic agents in conscious dogs.

In addition to their direct effects on cardiac contractility, a number of positive inotropic agents also induce, through direct peripheral vasodilation, a reduction in afterload which is of major importance in their beneficial effects in the treatment of congestive heart failure. However, the induced increase in cardiac output can indirectly improve perfusion of peripheral vessels through a flow-mediated mechanism. Thus, the goal of the present study was to compare the direct peripheral vasomotor effects assessed in the iliac vascular bed of four positive inotropic agents: DPI 201-106, ouabain, milrinone and dobutamine, in the presence and absence of simultaneous changes in cardiac function. These drugs were administered either through intravenous or intra-arterial (aorto-iliac catheter) routes in 6 conscious dogs, chronically instrumented for the measurement of heart rate, arterial pressure, left ventricular dP/dt, iliac artery blood flow and iliac artery diameter (sonomicrometry). Intravenous doses were selected as those inducing equipotent positive inotropic responses whereas intra-arterial doses were below those required to induce any significant change in systemic hemodynamics. Ouabain decreased and milrinone increased both iliac blood flow and diameter after either intravenous or intra-arterial administrations. In contrast, iliac blood flow did not change after intra-arterial administration of DPI 201-106 and dobutamine whereas iliac diameter was not modified by DPI 201-106 and even decreased with dobutamine. After intravenous administration, DPI 201-106 but not dobutamine, increased both iliac blood flow and diameter. Thus, this experimental preparation can differentiate inotropic agents with direct vasodilating (milrinone) or constricting (ouabain) properties and those (DPI 201-106 and dobutamine) with indirect vasodilating effects most likely mediated by the improvement in cardiac function.

Acetylcholine↗
PubMed1991

The L-arginine-nitric oxide pathway in the canine femoral vascular bed: in vitro and in vivo experiments.

Vascular endothelial cells synthesize nitric oxide from L-arginine, and this pathway can be inhibited by various analogues of L-arginine, including NG-nitro L-arginine methyl ester (L-NAME). To investigate the role of this pathway in the regulation of femoral arterial tone, the effect of L-NAME was studied in vitro in isolated canine femoral arteries suspended in organ chambers for isometric tension recording, and in vivo in conscious dogs chronically instrumented for the measurement of iliac blood flow and iliac artery diameter. In vitro, L-NAME induced an endothelium-dependent contraction, inhibited the endothelium-dependent relaxations to acetylcholine or bradykinin, and potentiated the relaxation evoked by the nitric oxide donor SIN-1. In vivo, locally administered L-NAME induced a decrease in iliac artery diameter and an increase in iliac resistance, potentiated the iliac responses to the organic nitrate nitroglycerin, but did not affect the iliac responses to the endothelium dependent vasodilator acetylcholine. Thus, in the canine femoral vascular bed: a) basal release of nitric oxide contributes in vivo to the maintenance of a permanent vasodilator tone at the level of both large conductance and small resistance vessels; b) the endothelium-dependent relaxations to acetylcholine and bradykinin in vitro are mostly mediated through the release of nitric oxide from L-arginine; c) the endothelium-dependent relaxations to acetylcholine in vivo are probably mediated by a relaxing factor distinct from nitric oxide, or by a nitric oxide-like molecule released from endothelial pools; and d) removal of the NO-mediated vasodilator tone by L-NAME leads to a supersensitivity to nitrovasodilators, both in vitro and in vivo.

Acetylcholine↗
PubMed1991

Regional coronary haemodynamic effects of two inhibitors of nitric oxide synthesis in anaesthetized, open-chest dogs.

1. The role of endothelial nitric oxide synthesis from L-arginine in the regulation of coronary vascular tone and myocardial tissue perfusion was evaluated in anaesthetized, open-chest dogs. Coronary blood flow was measured with an electromagnetic flow probe placed around the left circumflex coronary artery. Coronary vascular resistance was calculated from mean arterial blood pressure and mean coronary blood flow, whereas regional myocardial tissue flow was determined by use of the radioactive microspheres technique. 2. NG-monomethyl L-arginine (L-NMMA) and NG-nitro-L-arginine methyl ester (L-NAME), administered directly into the left circumflex artery, induced a small increase in arterial blood pressure and an increase in coronary vascular resistance. However, myocardial tissue perfusion, assessed by the microspheres technique (whether subendocardial, subepicardial, or transmural), was unaffected by L-NMMA or L-NAME. 3. Acetylcholine, administered intracoronarily, induced an increase in left circumflex coronary blood flow and a decrease in coronary vascular resistance, without affecting systemic haemodynamics. This coronary vasodilator effect of acetylcholine was markedly inhibited by L-NMMA and L-NAME, the latter being a more potent antagonist than the former. 4. These results indicate that the endothelial L-arginine pathway is largely responsible for the coronary vasodilator effect of acetylcholine. However, although basal release of nitric oxide from L-arginine apparently contributes to the regulation of resting coronary vascular tone, blockade of this pathway does not affect myocardial tissue perfusion, possibly because of compensatory mechanisms occurring at the level of small arterioles and/or capillaries.

Acetylcholine↗
PubMed1991

Opposed responses of large and small coronary arteries to propranolol during exercise in dogs.

This study was carried out to determine the relative role of alpha- and beta-adrenoceptors at the level of large epicardial and small resistance coronary arteries when sympathetic tone is increased by exercise. The responses of left circumflex coronary diameter and blood flow were examined at rest and during treadmill exercise in seven chronically instrumented dogs during control conditions (saline) and after propranolol administration (1 mg/kg) either alone or in combination with phentolamine (1.5 mg/kg). In control conditions, graded treadmill exercise (5, 10, and 12 km/h) resulted in a progressive increase in coronary artery diameter and decrease in coronary vascular resistance. After propranolol, coronary vascular resistance slightly increased at rest and then progressively decreased during exercise. Surprisingly, coronary artery diameter significantly decreased at rest as well as throughout the exercise period. Phentolamine significantly reduced the propranolol-induced effects on coronary arterial diameter but did not restore the exercise-induced dilation of the large coronary arteries observed during control conditions. In addition, phentolamine prevented the propranolol-induced increase in coronary vascular resistance at rest and reinforced the exercise-induced decrease in coronary vascular resistance observed under propranolol. Thus beta-adrenoceptors are essential in the mediation of exercise-induced dilation of large coronary arteries. In contrast, activation of beta-adrenoceptors is only partially responsible for the decrease in coronary vascular resistance during exercise. Finally, constriction of large coronary arteries after propranolol is mainly explained by the unmasking of alpha-adrenergic tone at rest, but other mechanisms are involved during exercise.

Animals↗