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Biomedical subjects

A Berdeaux

Publications and source records attributed to A Berdeaux.

At least 73 records · Page 4Linked to original sources
PubMed1992

[Correlations between plasma concentrations of atrial natriuretic factor and right ventricular function in patients with severe cardiac failure].

The atrial natriuretic factor (ANF) is secreted by the atria in mild and moderate cardiac failure but, during the evolution of the cardiac failure, the ventricles are also recruited and secrete ANF. In order to investigate the relation between plasma ANF and Doppler echocardiographic parameters of severe cardiac failure, the concentrations were measured simultaneously in 20 patients with NYHA Class III and IV cardiac failure (10 due to ischaemic and 10 due to primary dilated cardiomyopathy) despite optimal medical treatment including an angiotensin converting enzyme inhibitor. Overall, there was a weak negative correlation between the plasma ANF concentrations and the decrease in right ventricular surface area (r = -0.58, p less than 0.005, n = 20 patients). This relation was highly significant in ischaemic cardiomyopathy (r = -0.81, p less than 0.002, n = 10 patients) and not significant in primary dilated cardiomyopathy (r = -0.29, NS, n = 10 patients). No relationship was observed between plasma ANF and other echocardiographic parameters (atrial surface area, right and left ventricular dimensions, left ventricular ejection fraction and mass) or with Doppler aortic indices (acceleration, maximum and mean velocities, aortic velocity-time integrals). However, plasma ANF was related to the velocity of mitral regurgitant jets (r = -0.70, p less than 0.01) which is dependent on left ventricular pump function. These results show that plasma ANF concentrations are only related to right ventricular systolic function and the velocity of mitral regurgitation in patients with severe cardiac failure.

Adult↗
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

Clearance of atrial natriuretic peptide in patients with cirrhosis. Role of liver failure.

In non-cirrhotic patients, splanchnic, renal and pulmonary vascular beds are involved in the plasma clearance for atrial natriuretic peptide (ANP). In patients with cirrhosis, endogenous plasma ANP clearance by these vascular beds has not been systematically studied. In addition, the influence of the severity of liver failure on plasma ANP clearance is not known. Thus, in this study we determined plasma ANP clearance by splanchnic, renal and pulmonary circulations using both arteriovenous differences in plasma ANP concentrations and organ plasma flow in 11 patients with cirrhosis. The role of forearm circulation in plasma ANP extraction was also studied. Splanchnic plasma ANP extraction was 29 +/- 7% (mean +/- S.E.) and splanchnic plasma ANP clearance was 404 +/- 130 ml/min (n = 7). Renal plasma ANP extraction and clearance were 32 +/- 8% and 191 +/- 57 ml/min, respectively. Forearm plasma ANP extraction was 11 +/- 4%. Pulmonary plasma ANP extraction and clearance were 8 +/- 5% and 312 +/- 272 ml/min, respectively. A significant negative correlation was found between logarithm of serum bilirubin concentration, on one hand, and splanchnic and forearm plasma ANP extraction, on the other. A significant negative correlation was found between Pugh's score, on one hand, and renal plasma ANP extraction and clearance, on the other. No significant correlation was found between the severity of liver failure and pulmonary plasma ANP extraction and clearance. As a result, we conclude that in cirrhotic patients splanchnic, renal, forearm and pulmonary vascular beds are involved in plasma ANP extraction and clearance. Plasma ANP extraction and/or clearance may be attenuated in the splanchnic, renal and forearm circulations due to liver failure.

Atrial Natriuretic Factor↗
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

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

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

Amiodarone: influence of the route of administration on thyroid status and cardiac beta-adrenoceptors in the rat.

The influence of 2 different routes of amiodarone (AMIO) administration, oral gavage (OG) and subcutaneous injection (SC), on the density of cardiac beta-adrenoceptors (Bmax), hepatic type I 5' iodothyronine deiodinase (5' DI) and thyroid hormone serum concentrations was studied. Compared with respective control values, AMIO treatment (50 mg/kg per day, 7 days) via both OG and SC routes significantly lowered Bmax (OG: 14.6 +/- 1.92 vs 18.2 +/- 1.03 fmol/mg and SC: 16.6 +/- 2.34 vs 19.1 +/- 2.05 fmol/mg) and 5' DI activity (from 409 to 85 and 340 to 47 fmol I-/mg per min, respectively). The SC route induced a fall in thyroid secretion and a generalized hypothyroidism (decreased serum FT4 and FT3, inhibition of body weight gain. The OG route did not modify thyroid secretion. These results demonstrated that the effects on cardiac beta-receptor density in the SC group might be due to the generalized hypothyroidism and that AMIO produced its specific cardiac effects only after oral route medication, suggesting that the oral route is the best choice for studying AMIO cardiac effects on beta-receptor density.

Administration, Oral↗
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↗
PubMed1991

Lidocaine and cardiovascular reflex responses to simulated orthostatic stress in normal volunteers.

The interactions of lidocaine with baroreceptor reflexes during simulated orthostatic stress or moderate volume depletion were investigated in healthy volunteers using the lower body negative pressure (LBNP) test. Cardiopulmonary baroreceptors were selectively unloaded at low levels of LBNP (-15 mm Hg) since the central venous pressure (CVP) decreased (-1.4 +/- 0.3 mm Hg) without changes in arterial pressure (AP) and heart rate (HR) but significant increases in forearm vascular resistance (FVR) and plasma noradrenaline (PNA). Cardiopulmonary as well as arterial baroreflexes were both unloaded at higher levels of LBNP (-40 mm Hg) since the CVP (-3.4 +/- 0.4 mm Hg) and systolic AP (-10 +/- 3 mm Hg) decreased whereas FVR, PNA, and plasma renin activity (PRA) increased further (all p less than 0.05). Following lidocaine infusion (serum level of 3.8 +/- 0.2 micrograms/ml), the AP, HR, FVR, and PNA increased and CVP decreased (p less than 0.05). Compared to LBNP performed under saline, lidocaine did not alter the LBNP (-15 mm Hg)-induced changes in cardiovascular and biological parameters but significantly decreased the induced rises in HR, FVR, PNA, and PRA at a LBNP of -40 mm Hg (p less than 0.05). In an additional study, it was also demonstrated that lidocaine significantly decreased the sensitivity of the reflex-mediated bradycardia following phenylephrine injection and attenuated the vasoconstrictor response to the cold pressor test taken as a nonspecific somatic pressor reflex.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
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↗
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

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

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↗