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Biomedical subjects

R J Bache

Publications and source records attributed to R J Bache.

At least 109 records · Page 6Linked to original sources
PubMed1990

Effect of pinacidil on myocardial blood flow in the presence of a coronary artery stenosis.

This study examined the effect of pinacidil on transmural distribution of myocardial blood flow during normal conditions and in the presence of a coronary artery stenosis. Studies were performed in 11 awake dogs; blood flow was measured with radioactive microspheres. Two doses of pinacidil were administered to decrease mean arterial pressure (MAP) by approximately 10 mm Hg (low dose, 0.18 +/- 0.02 mg/kg) and 20 mm Hg (high dose, 0.32 +/- 0.03 mg/kg). Measurements were performed during unimpeded arterial inflow and with two levels of coronary stenosis that limited blood flow to approximately 60% above (moderate stenosis) and approximately 30% above basal flow (severe stenosis). With no stenosis, coronary flow increased 227 +/- 17% after low-dose and 321 +/- 31% after high-dose pinacidil (each p less than 0.01). During control conditions, subendocardial (endo) flow exceeded subepicardial (epi) flow (endo/epi ratio = 1.33). This ratio was not changed by low-dose pinacidil but decreased to 0.93 after high-dose pinacidil (p less than 0.05). During high-dose pinacidil, a coronary stenosis caused uniform reduction of blood flow across the left ventricular wall, with no further significant change in the ratio of endo/epi flow. With low-dose pinacidil, both moderate and severe degrees of stenosis caused redistribution of flow away from the subendocardium similar to that observed with high-dose pinacidil. Although a stenosis that limited the increase in mean coronary flow after pinacidil administration to 162% of the predrug control value had a 95% probability of not causing a decrease in absolute subendocardial flow, the data suggest that pinacidil could have potential for aggravating subendocardial ischemia in severe occlusive coronary artery disease.

Animals↗
PubMed1990

Effect of pinacidil on myocardial blood flow in the chronically pressure overloaded hypertrophied left ventricle.

This study examined the effect of pinacidil on the transmural distribution of myocardial blood flow in the chronically pressure overloaded hypertrophied left ventricle. Studies were performed in six dogs in which banding of the ascending aorta had resulted in an 88% increase in left ventricular mass, as well as in six normal control animals. Two doses of pinacidil were administered to decrease mean arterial pressure by approximately 10 mm Hg (low dose) and 20 mm Hg (high dose). Animals with hypertrophy required significantly smaller drug doses to achieve the desired reductions in arterial pressure. During control conditions mean myocardial blood flow was significantly higher in animals with hypertrophy (1.90 +/- 0.21 ml/min/g) than in normal animals (1.12 +/- 0.08 ml/min/g; p less than 0.05). Subendocardial flow (endo) exceeded subepicardial flow (epi) in normal dogs during control conditions (endo/epi = 1.41 +/- 0.13), but not in animals with hypertrophy (endo/epi = 1.06 +/- 0.06; p less than 0.05). Pinacidil caused coronary vasodilation with similar relative increases in blood flow in both normal and hypertrophied hearts, so that after pinacidil, absolute blood flow rates remained higher than normal in animals with hypertrophy. Pinacidil caused a redistribution of blood flow away from the subendocardium in normal hearts (endo/epi = 0.90 +/- 0.11 during high-dose pinacidil) and in hearts with hypertrophy (endo/epi = 0.81 +/- 0.13 during high-dose pinacidil). The endo/epi ratios during high-dose pinacidil were not significantly different between the two groups. This study demonstrates that pinacidil is a potent coronary vasodilator in both normal and hypertrophied hearts.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Effect of coronary stenosis on myocardial blood flow during exercise in the chronically pressure-overloaded hypertrophied left ventricle.

This study was performed to determine if a coronary artery stenosis would result in more-severe perfusion abnormalities in hypertrophied compared with normal canine hearts during exercise. Studies were performed in eight normal control dogs and in seven adult dogs in which a 67% increase in left ventricular mass wa produced by banding the ascending aorta at 9 weeks of age. Myocardial blood flow was measured by the microsphere method during treadmill exercise in the presence of a coronary artery stenosis that decreased distal coronary perfusion pressure to 55 or 42 mm Hg. At a coronary pressure of 55 mm Hg, mean myocardial blood flow was decreased by 23 +/- 5% in normal control dogs but was decreased by 53 +/- 10% in dogs with left ventricular hypertrophy (LVH) (p less than 0.05, comparing normal vs. LVH dogs). Similarly, at a coronary pressure of 42 mm Hg, mean blood flow was decreased by 53 +/- 6% below control in normal dogs but was decreased by 76 +/- 5% below control values in dogs with LVH (p less than 0.01, comparing normal vs. LVH dogs). In both groups of dogs, the stenosis caused a gradient of hypoperfusion, worsening from epicardium to endocardium. However, for each level of stenosis, subendocardial blood flow and the ratio of subendocardial to subepicardial blood flow was less in LVH than in normal canine hearts. These findings demonstrate that the presence of LVH secondary to long-term pressure overload is associated with an increased vulnerability to myocardial hypoperfusion during exercise in the presence of a coronary artery stenosis.

Animals↗
PubMed1990

Correlation between transmural high energy phosphate levels and myocardial blood flow in the presence of graded coronary stenosis.

Spatially localized nuclear magnetic resonance spectroscopy was used to investigate with transmural differentiation the response of myocardial high energy phosphate compounds and inorganic orthophosphate (Pi) to graded reductions in coronary blood flow caused by sustained coronary stenosis. In an open-chest model, localized 31P nuclear magnetic resonance spectra from five layers across the left ventricular wall were obtained simultaneously with transmural blood flow measurements during control conditions and during sustained graded reductions in intracoronary pressure. Both the blood flow, and high energy phosphate and Pi contents displayed transmural heterogeneity in response to decreases in intracoronary pressure. The subendocardial creatine phosphate (CP) level remained unchanged as blood flow was reduced to approximately 0.7 ml/min/g wet wt and decreased precipitously beyond this critical flow level. The relation between CP and flow in the midmyocardium and especially in the subepicardium was more complex. Subepicardial CP content did not correlate well with blood flow; however, in cases in which a coronary stenosis resulted in subendocardial hypoperfusion but subepicardial flow was near or above normal, a close correlation was present between subepicardial and subendocardial CP levels. ATP levels in all layers remained unaltered until blood flow was severely reduced. These results demonstrate that 1) the myocardial high energy phosphate and Pi levels at any transmural layer are not generally determined by O2 and blood flow limitation under basal conditions; 2) during subtotal coronary occlusion, increased oxygen extraction is able to meet myocardial needs until a critical level of stenosis is reached; 3) below a critical flow level, subendocardial CP and Pi contents are closely correlated with absolute subendocardial blood flow; and 4) in the presence of a coronary stenosis, subepicardial CP and Pi contents may change even in the absence of perfusion deficit secondary to loss of subendocardial function.

Adenosine Triphosphate↗
PubMed1989

Spectroscopic imaging and spatial localization using adiabatic pulses and applications to detect transmural metabolite distribution in the canine heart.

Adiabatic pulses have been employed in spectroscopic imaging and relaxation rate measurements at 4.7 T to demonstrate the feasibility of obtaining spectroscopic data from the complete sensitive volume of a surface coil using the surface coil as a transmitter and receiver. With conventional B1 sensitive pulses, spectroscopic localization or imaging techniques, such as chemical-shift imaging, yield resonance intensities that are distorted severely as a function of space, and maximal signal is detected from a small region within the complete sensitive volume of the coil. With adiabatic pulses, however, this problem is eliminated completely. In addition, a new method of spatial localization is introduced. This method, referred to as FLAX-ISIS, is a derivative of longitudinally modulated Fourier series window and ISIS approaches and utilizes adiabatic inversion and excitation pulses. The method allows construction of localized spectra for multiple regions along the surface coil axis by postacquisition data manipulation of a single set of free induction decays. These techniques were applied to the study of the myocardium using an implanted surface coil in an instrumented closed-chest canine model and in an open-chest preparation. The results demonstrate that one-dimensional techniques are adequate for transmural detection of metabolites provided signal origin is restricted to a column perpendicular to the left ventricle wall.

Animals↗
PubMed1989

Transmural metabolite distribution in regional myocardial ischemia as studied with 31P NMR.

Phosphorus-31 nuclear magnetic resonance (31P NMR) has been applied to study the canine heart prior to and during regional myocardial ischemia induced by partial flow reduction in the left anterior descending coronary artery (LAD). NMR data were acquired in a transmural fashion by restricting the signal to a column perpendicular to the heart wall using B0 gradients and obtaining spectroscopic spatial resolution along the third dimension using the B1 gradient and adiabatic excitation. With this approach, transmural spectra were accumulated in five separate voxels spanning the wall of the left ventricle from the epicardium to the endocardium. In the normal canine myocardium the levels of high-energy phosphates CP and ATP were relatively constant throughout the left ventricular wall, with only minor evidence of free inorganic phosphate in any of the transmural voxels. However, during sustained partial occlusion of the LAD, significant regional differences between the epi- and the endocardium were noted. The data demonstrate the importance of studying cardiac bioenergetics with transmural differentiation.

Animals↗
PubMed1989

Metabolic consequences of coronary stenosis. Transmurally heterogeneous myocardial ischemia studied by spatially localized 31P NMR spectroscopy.

Coronary stenosis results in transmurally non-uniform blood flow with the inner layers of the left ventricular wall typically suffering a more severe hypoperfusion relative to the outer layers. Coupled with numerous other transmural non-uniformities such as systolic tension development and oxygen needs, the heterogeneous blood flow distribution in the presence of coronary stenosis is expected to result in transmurally heterogeneous ischemia. All previous NMR spectroscopy studies of myocardial metabolism and bioenergetics under normal and ischemic conditions treated the organ as a homogeneous tissue. We have utilized spatially localized 31P NMR spectroscopy together with non-NMR measurements of regional blood flow to study the myocardium with transmural spatial differentiation under normal and flow-restricted conditions. 31P NMR and blood flow data obtained concurrently on each heart revealed that sustained coronary artery stenosis resulted in transmurally non-uniform ischemia which largely paralleled the hypoperfusion pattern. The reduction in creatine phosphate content (with consequent elevation of Pi) and hypoperfusion was tightly correlated in the subendocardium for flow rates less than approximately 0.7 mL/min per g wet myocardium. The high energy phosphate and Pi content of the epicardium, however, was responsive not only to the flow to this region but also to the extent of ischemia in the subendocardial layers. These results document the utility of localized NMR spectroscopy in physiologic research and suggest potential biomedical applications due to the tight correlation noted between alterations in blood flow and changes in the phosphorylated metabolite levels detected by 31P NMR.

Animals↗
PubMed1989

Alpha-adrenergic effects of dopamine and dobutamine on the coronary circulation.

After beta-adrenergic blockade, dopamine causes coronary vasoconstriction that is blocked by non-selective alpha-adrenergic antagonists. This study was carried out to determine the relative importance of alpha 1- and alpha 2-adrenoceptors in mediating coronary vasoconstriction in response to dopamine. Because dobutamine has been reported to cause alpha-adrenergic stimulation, the response to dobutamine was also examined. The circumflex coronary artery was cannulated and perfused at a constant blood flow rate in 14 dogs; coronary vasomotor responses were assessed from changes in perfusion pressure. Central effects were eliminated by vagotomy and stellate ganglionectomy; propranolol (1 mg/kg i.v.) was administered to block beta-adrenergic effects. The coronary responses to intracoronary bolus doses of dopamine and dobutamine were determined; the effects of selective alpha 1-blockade with prazosin (600 micrograms/kg i.v.) and selective alpha 2-blockade with idazoxan or rauwolscine (1-5 micrograms/kg per min intracoronary for 10 min) were examined. Dopamine produced dose-related coronary vasoconstriction; this response was not significantly altered by alpha 1-blockade with prazosin, but was abolished by the addition of alpha 2-adrenergic blockade with idazoxan or rauwolscine. Dobutamine did not produce coronary vasoconstriction at any dose tested. These data demonstrate that coronary vasoconstriction produced by dopamine is mediated through postjunctional alpha 2-adrenergic receptors.

Animals↗
PubMed1989

Vasomotor activity of moderately well-developed canine coronary collateral circulation.

This study examined the ability of moderately well-developed coronary collateral vasculature to undergo vasoconstriction in response to alpha-adrenergic agonists, vasopressin and angiotensin, and vasodilation in response to nitroglycerin. Studies were performed in 20 dogs 4-16 wk after left anterior descending coronary artery occlusion had been produced by an Ameroid constrictor or hollow intravascular plug. Collateral flow was estimated from retrograde flow from the cannulated left anterior descending artery. Tissue flow was measured with microspheres. Agonists were introduced into the left main coronary artery to reach collaterals arising from the left circumflex and septal arteries. Vasopressin and angiotensin II decreased retrograde flow from 22.7 +/- 5.5 to 15.5 +/- 2.7 and from 19.2 +/- 2.8 to 14.3 +/- 1.9 ml/min, respectively (each P less than 0.05). Both agents also significantly decreased tissue flow to normally perfused and collateral dependent myocardium. Neither the selective alpha 1-adrenergic agonist phenylephrine nor the alpha 2-agonist B-HT 933 decreased retrograde flow. Nitroglycerin increased retrograde flow by 63 +/- 27% (P less than 0.01). Thus, although the moderately well-developed coronary collateral circulation is capable of vasoconstriction in response to vasopressin and angiotensin II, these data fail to support a role for alpha-adrenergic mechanisms in modulating collateral flow.

Adrenergic alpha-Agonists↗
PubMed1989

Coronary flow during exercise after selective alpha 1- and alpha 2-adrenergic blockade.

This study was carried out to determine the relative importance of alpha 1- and alpha 2-adrenergic vasoconstriction in opposing the increase in coronary blood flow, which occurs during exercise. The response of left circumflex coronary artery blood flow was examined during treadmill exercise in 16 chronically instrumented dogs during control conditions, after selective alpha 1-adrenergic blockade with intracoronary prazosin, and after alpha 2-blockade with intracoronary idazoxan. During control conditions, graded treadmill exercise resulted in progressive increases of coronary blood flow and decreases of coronary vascular resistance. Prazosin produced highly selective alpha 1-adrenergic blockade; coronary blood flow was significantly higher and coronary vascular resistance significantly lower during all but the heaviest exercise stage after prazosin. Idazoxan produced highly effective, but only moderately selective, alpha 2-adrenergic blockade. However, after idazoxan, coronary blood flow and coronary vascular resistance during exercise were not significantly different from control. Combined alpha 1- and alpha 2-adrenergic blockade was not more effective in increasing coronary blood flow during exercise than was alpha 1-adrenergic blockade alone. These data support a role for alpha 1-adrenergic coronary vasoconstriction in limiting the increase in coronary blood flow, which occurs during exercise, but do not support a role for alpha 2-mediated coronary vasoconstriction during exercise.

Adrenergic alpha-Antagonists↗
PubMed1989

Cumulative deterioration of myocardial function after repeated episodes of exercise-induced ischemia.

To determine whether progressive regional myocardial dysfunction occurs after repetitive episodes of exercise-induced ischemia, 10 dogs were instrumented with ultrasonic microcrystals for determination of regional myocardial wall thickening, circumflex artery electromagnetic flow probes, and hydraulic coronary artery occluders. Dogs performed treadmill exercise in the presence of a coronary artery stenosis, which limited coronary blood flow to control levels. Dogs performed a single 10-min exercise period one day and three identical runs separated by 1-h rest periods on the alternate day. At rest before the first exercise period, circumflex wall thickening was 18.8 +/- 6.7% and increased to 25.5 +/- 10.6% during exercise before the application of coronary stenosis. On the day that three exercise trials were performed, circumflex systolic wall thickening at rest before the third exercise period (9.7 +/- 4.0%) and during exercise without coronary stenosis (17.3 +/- 7.3%) were both significantly lower than during the first exercise period (P less than 0.0125). During exercise with stenosis, circumflex systolic wall thickening fell to 4.6 +/- 4.7% during a single run, and 5.0 +/- 2.0% during the third of three consecutive runs. Wall thickening was significantly lower 2 h after the third consecutive run (9.1 +/- 2.4%) than 2 h after a single period of exercise-induced ischemia (14.8 +/- 7.6%; P 0.0125). Transmural myocardial blood flow to circumflex myocardium during the third period of exercise-induced ischemia (0.93 +/- 0.47 ml.min-1.g-1) was not different than during the single period of exercise (0.84 +/- 0.47 ml.min-1.g-1). It is concluded that repetitive episodes of exercise-induced ischemia result in cumulative postexercise regional myocardial dysfunction.

Animals↗
PubMed1989

Oxygen consumption and coronary reactivity in postischemic myocardium.

Coronary vascular responses in regions of reversible postischemic myocardial contractile dysfunction (stunned myocardium) were examined in chronically instrumented, awake dogs. Left anterior descending coronary artery blood flow and oxygen extraction, aortic and left ventricular pressures, and regional myocardial segment shortening were determined. Regional myocardial blood flow was measured with microspheres. Coronary reactive hyperemia and vasodilator reserve, and regional myocardial oxygen consumption were determined. Three sequential 10-minute left anterior descending coronary artery occlusions separated by 30-minute reperfusion periods resulted in progressive postischemic dysfunction so that 1 hour after the final coronary artery occlusion, myocardial segment shortening was reduced to 37% of baseline. Despite this decrease in contractile function, left anterior descending artery flow (19.6 +/- 2.6 vs. 18.4 +/- 3.0 ml/min), myocardial blood flow and the transmural distribution of flow measured with microspheres, and regional myocardial oxygen consumption were unchanged. Although the coronary vasodilator reserve in response to adenosine was unaltered (63 +/- 9 vs. 70 +/- 15 ml/min), the reactive hyperemia response to a 10-second coronary occlusion was decreased in intensity (debt repayment ratio = 474 +/- 78% vs. 322 +/- 74%; p less than 0.05) and duration (57 +/- 9.1 vs. 35 +/- 4.5 seconds; p less than 0.05), while the peak flow response was unchanged (57 +/- 6.8 vs. 60 +/- 7.1 ml/min). Thus, in the intact awake animal postischemic myocardial contractile dysfunction was not associated with decreased myocardial oxygen consumption and did not impair the normal relation between coronary blood flow and myocardial oxygen utilization. Although coronary vessels showed a normal ability to vasodilate in response to adenosine, coronary reactive hyperemia was reduced.

Animals↗
PubMed1989

Effect of atrial natriuretic peptide on coronary collateral blood flow.

This study was carried out to examine the effects of atrial natriuretic peptide on coronary collateral blood flow. Studies were performed in nine adult mongrel dogs 3.4 months after embolic occlusion of the left anterior descending coronary artery had been performed to stimulate collateral vessel growth. At the time of study the anterior descending coronary artery was cannulated to allow estimation of interarterial collateral flow from measurements of retrograde blood flow. Injection of radioactive microspheres during retrograde flow collection allowed simultaneous determination of continuing tissue flow for evaluation of microvascular collateral communications. Atrial natriuretic peptide in doses of 20 and 200 micrograms administered into the left atrium resulted in 17 +/- 3.0% and 34 +/- 4.5% increases in retrograde flow, respectively (each p less than 0.01). Tissue flow in the collateral dependent myocardial region did not change in response to atrial natriuretic peptide. After the larger dose of atrial natriuretic peptide, the administration of nitroglycerin (10 micrograms/kg into the left atrium) caused no further increase of retrograde blood flow, and no further decrease of collateral vascular resistance. These data indicate that atrial natriuretic peptide causes vasodilation of moderately well-developed interarterial coronary collateral vessels.

Animals↗
PubMed1989

The role of alpha 1- and alpha 2-adrenergic receptors in mediation of coronary vasoconstriction in hypoperfused ischemic myocardium during exercise.

This study was carried out to test the hypothesis that adrenergic coronary vasoconstriction limits blood flow to hypoperfused regions of myocardium during exercise. The vasoconstrictor influence of alpha-adrenergic receptor subtypes was assessed by use of selective adrenergic blocking agents. Dogs chronically instrumented with a circumflex coronary artery hydraulic occluder and an intra-arterial catheter underwent treadmill exercise in the presence of a coronary stenosis that decreased distal perfusion pressure to 40 mm Hg. Myocardial blood flow was measured with radioactive microspheres (15 microns) before and during selective alpha 1- or alpha 2-adrenergic receptor blockade produced by intracoronary infusion of prazosin (1 microgram/kg/min x 10 min) or idazoxan (1 microgram/kg/min x 10 min), respectively. Coronary perfusion pressure was held equal before and during receptor blockade with the hydraulic occluder. Compared with control exercise, subendocardial blood flow increased during alpha 1-receptor blockade with prazosin from 0.60 +/- 0.14 to 1.12 +/- 0.17 ml/min/g (p less than 0.05), and mean transmural flow increased from 1.07 +/- 0.19 to 1.60 +/- 0.22 ml/min/g (p less than 0.05). In contrast, subendocardial and mean transmural blood flow were not different from control during selective alpha 2-adrenergic receptor blockade with idazoxan (0.48 +/- 0.10 vs. 0.67 +/- 0.14 ml/min/g, p = 0.33, and 0.82 +/- 0.15 vs. 1.02 +/- 0.20 ml/min/g, p = 0.45, respectively). These data indicate that even in the presence of a coronary stenosis that causes substantial myocardial underperfusion during exercise, residual coronary vasoconstrictor tone is present in ischemic myocardium, and this vasoconstriction is mediated predominantly by the alpha 1-adrenergic receptor.

Animals↗
PubMed1989

Effects of calcium entry blockade on myocardial blood flow.

The calcium entry-blocking drugs produce effects on the coronary vasculature that might be expected to exert anti-ischemia activity. Although these agents cause little vasodilation of the epicardial coronary arteries during basal conditions, they block vasoconstriction that can increase stenosis severity during isometric exercise and interrupt coronary artery spasm in patients with variant angina. Administration of the calcium blockers causes transient vasodilation of the coronary resistance vessels, followed by decreased responsiveness to a brief ischemic stimulus. This results in decreased coronary reactive hyperemia after transient coronary occlusion. By preventing excessive ischemic vasodilation of the resistance vessels, these agents can enhance perfusion of the subendocardium distal to a flow-limiting coronary stenosis. The calcium entry blockers have relatively little effect on the immature coronary collateral vessels that exist at the time of acute coronary occlusion. Diltiazem, however, has been demonstrated to increase collateral blood flow in animals in which chronic coronary occlusion has resulted in growth of moderately well-developed collateral vessels.

Animals↗
PubMed1988

Combined effects of calcium antagonists and nitroglycerin on large coronary artery diameter.

Nitroglycerin and calcium antagonists are direct dilators of large coronary arteries. Their amelioration of myocardial ischemia may be in part related to their dilating action on coronary stenoses. The present study was done to determine if the effects of calcium antagonists and nitroglycerin on large coronary arterial diameter are additive. External circumflex coronary arterial diameter was measured by sonomicrometry in 16 awake, instrumented dogs. Intravenous nifedipine (mean dose 30 +/- 4 micrograms/kg) caused dilation of the circumflex coronary artery (4.01 +/- 0.13 to 4.10 +/- 0.12 mm, p less than 0.05). The addition of intravenous nitroglycerin (10 to 20 micrograms/kg) caused further coronary arterial dilation (4.10 +/- 0.12 to 4.13 +/- 0.12 mm, p less than 0.05). Intravenous verapamil (mean dose 520 +/- 77 micrograms/kg) also caused dilation of the circumflex coronary artery (4.14 +/- 0.35 to 4.26 +/- 0.35 mm, p less than 0.05). The addition of intravenous nitroglycerin caused further dilation (4.26 +/- 0.35 to 4.31 +/- 0.35 mm, p less than 0.05). Intravenous diltiazem (mean dose 640 +/- 140 micrograms/kg) caused circumflex coronary arterial dilation in four of the five dogs studied (mean change 4.14 +/- 0.36 to 4.21 +/- 0.33 mm). The addition of intravenous nitroglycerin caused further circumflex coronary dilation (4.21 +/- 0.33 to 4.26 +/- 0.33 mm, p less than 0.05). Therefore, the effects of nitroglycerin and each of these three calcium antagonists on large coronary diameter are additive, with the combination of nitroglycerin and the calcium antagonist causing more large coronary dilation than the calcium antagonist alone.

Animals↗
PubMed1988

Effects of atrial natriuretic peptide on coronary vascular resistance in the intact awake dog.

Atrial natriuretic peptide has been reported to cause vasoconstriction, vasodilation or no change of coronary vascular resistance in isolated perfused hearts or in open chest animal models. Because general anesthesia and acute surgical trauma may perturb baseline coronary hemodynamics and alter responses to experimental interventions, this study examined the effects of human atrial natriuretic peptide (arginine-102-tyrosine-126) and rat atriopeptin II (serine-103-arginine-125) on the coronary circulation of unsedated, awake dogs. Studies were performed in 12 chronically instrumented animals in which a surgically implanted electromagnetic flow probe and intracoronary catheter allowed measurement of left circumflex coronary blood flow during intraarterial administration of the atrial natriuretic peptides. Bolus doses of both human atrial natriuretic peptide and rat atriopeptin II produced dose-dependent coronary vasodilation; the threshold for coronary vasodilation was 0.2 micrograms/kg body weight for both agents. Coronary vasodilation produced by human atrial natriuretic peptide was not antagonized by adenosine receptor blockade or by cyclooxygenase inhibition with indomethacin. Thus, atrial natriuretic peptides produced dose-dependent coronary vasodilation in intact awake dogs that was not dependent on adenosine-mediated or prostaglandin-mediated mechanisms.

Animals↗