Topical application of bradykinin or capsaicin to abdominal visceral organs produces adrenergically mediated, reflex increases in mean arterial pressure and cardiac work. To determine the effects on coronary blood flow, the left main coronary artery of anesthetized cats was perfused at constant pressure with a servo-controlled pump. Cardiovascular parameters were measured during reflex stimulation before and after beta-adrenoceptor blockade with propranolol. Before propranolol, reflex activation led to increases in the double product and myocardial oxygen consumption, usually accompanied by increases in coronary blood flow. However, in 32% of the observations, decreases in flow were observed. During beta-adrenoceptor blockade, reflex stimulation produced increases in cardiac work, whereas the increases in coronary blood flow were attenuated. Marked decreases in average coronary blood flow were observed more frequently (42%). In the presence of propranolol, contrary to the unblocked state, increases in oxygen consumption were achieved by increased oxygen extraction. Subsequent alpha-adrenoceptor blockade with phentolamine abolished all reflex changes. These data indicate that during stimulation of abdominal visceral chemoreceptors, the major coronary response is vasodilation, but in a sizable fraction of cases, abdominal visceral reflexes can produce sympathetically mediated coronary vasoconstriction.
Intra-arterial administration of neuropeptide Y (NPY), a peptide endogenous to sympathetic nerves, increases coronary vascular resistance by 30-40%. To test whether blockade of prostaglandin synthesis altered the severity of the NPY-induced coronary vasoconstriction, dogs (n = 25) were anesthetized and instrumented to record hemodynamic parameters. In control animals (n = 11) paired infusions of NPY (42 nmol/3 min) were given at 0 and 120 min. NPY produced similar increases in coronary resistance by 10 min, 31 +/- 7% (mean +/- SD) with the first dose vs. 32 +/- 12% with the second dose. The increases in resistance were due to an initial decrease in coronary flow (10 +/- 6%) followed by a prolonged increase in aortic pressure (15-20% over 20 min). Each infusion of NPY decreased heart rate (-10 +/- 7%) but did not alter left ventricular dP/dt. The effects of NPY lasted 40-60 min. In a separate group, a cyclooxygenase inhibitor (COI), indomethacin (n = 6) or ibuprofen (n = 8), was given 1 h before the second dose of NPY. The increases in coronary resistance were blunted significantly after cyclooxygenase blockade from a predrug value of 36 +/- 13 to 19 +/- 12%. In these treated animals, the decrease (-12 +/- 6%) in coronary blood flow seen with the first dose of NPY was prevented (4 +/- 14%) during the second dose (P less than 0.05). Of the two drugs, ibuprofen appeared to restore coronary flow more than did indomethacin. Neither drug affected the base line or the NPY-elicited changes in aortic pressure, heart rate, dP/dt, or myocardial oxygen demands.(ABSTRACT TRUNCATED AT 250 WORDS)
Tomographic myocardial imaging with Tc-99m sestamibi during moderately severe partial coronary occlusion underestimated the area of the defect relative to Tl-201 or to the pathologic reference standard in dogs. Defect contrast was sharper with tomographic myocardial Tl-201 than with tomographic myocardial Tc-99m sestamibi during moderately severe partial coronary occlusion.
Intravenous norepinephrine increases glycerol release and blood flow in adipose tissue. The vasodilation may be an indirect effect of norepinephrine through the production of adenosine. Adenosine increases glucose uptake and inhibits lipolysis in vitro. To test whether adenosine regulates blood flow and/or metabolism in vivo, adenosine deaminase (ADA) was infused intra-arterially into the inguinal fat pads of anesthetized dogs. In unstimulated tissues, ADA (n = 7) significantly increased vascular resistance and significantly decreased glucose uptake compared with the effects of a control (boiled deaminase, n = 6) infusion. ADA completely blocked the norepinephrine-induced vasodilation (n = 6). No potentiation of basal or catecholamine-stimulated lipolysis was observed with ADA. The presence of ADA in the interstitial space was verified by analysis of lymph effluents. Interstitial levels of ADA were inversely correlated with the tissue contents of adenosine. These data support the hypothesis that adenosine is a regulator of blood flow in basal and stimulated adipose tissue. Adenosine also appears to regulate glucose uptake, but not lipolysis, in vivo.
Adenosine may mediate coronary vasodilation during work-related hyperemia and during ischemia. We tested whether adenosine blockade with 8-p-sulfophenyltheophylline (PSPT) prevented dobutamine-induced hyperemia or magnified the reductions in flow due to vasopressin. Control (n = 8) and test (n = 7) dogs received paired infusions of dobutamine (70 micrograms/min iv for 5 min). Test dogs received PSPT (10 mg/kg iv) between doses. In both groups, paired infusions elicited comparable increases in oxygen consumption. However, in test dogs, the hyperemia was reduced significantly. Thus adenosine mediates the hyperemia of dobutamine. Separately, control dogs (n = 9) received vasopressin (0.6 microgram ic over 5 min); test dogs (n = 7) received PSPT before vasopressin. Vasopressin maximally increased coronary resistance by 3 min; effects were gone by 10 min. With PSPT, coronary resistance was increased further and remained high beyond 10 min. Thus adenosine-mediated vasodilation moderates the severity and duration of ischemia. These results indicate the importance of adenosine in mediating coronary flow during increased demand and reduced supply.
We examined the role of adenosine in modulating the coronary constrictor effect of neuropeptide Y (NPY). Anesthetized dogs (n = 22) were instrumented to record hemodynamics and to collect arterial and coronary venous blood. In control dogs (n = 7), during the first 30 min before NPY, baseline coronary resistance fell slightly. By 10 min after NPY (42 nmol over 4 min), coronary resistance was increased by 30% and fell slowly to pre-NPY levels over the ensuing hour. Intravenous (7.5 mg/kg, n = 3) or intracoronary (to 100 microM arterial concentration, n = 12) infusion of 8-p-sulfophenyltheophylline (8-THEO) blocked the vasodilator effects of adenosine but did not alter the peak dilation seen with papaverine or reactive hyperemia. Over 30 min before NPY, infusion of 8-THEO increased baseline resistance by 31% as it reduced coronary blood flow, despite no change in other hemodynamic parameters or myocardial oxygen consumption. The coronary constrictor effect of NPY was magnified in the presence of adenosine receptor blockade. At 3 min, coronary resistance was increased by 34%, at 5 min by 52%, and at 10 min by 59%. The effect of adenosine receptor blockade on constriction due to NPY could not be attributed to a nonspecific alteration in cardiac function or oxygen consumption. In addition, the increase in baseline coronary resistance following receptor blockade correlated with the worsening of the coronary constriction following NPY (r = 0.48, P less than 0.05). Thus it appears that adenosine modulates an imposed constriction of coronary vessels and acts as a "host defense" to restore coronary tone toward normal.
We previously reported that coronary constriction following neuropeptide Y (NPY) was alleviated by cyclooxygenase blockade. To determine the role of thromboxane A2 (TxA2), anesthetized dogs received two paired doses of NPY given 2 h apart. Nine control dogs received NPY alone. Nine test dogs received one of three TxA2 receptor antagonists given between the doses of NPY. Also, five dogs received NPY during which prostaglandins were measured. In controls, NPY decreased coronary blood flow and increased aortic pressure; coronary resistance was increased significantly. Heart rate fell, and myocardial oxygen consumption was unchanged. Thromboxane receptor blockers significantly relieved the coronary constrictor effect of NPY. The reduction in coronary blood flow was blunted, while heart rate, first derivative of left ventricular pressure, and myocardial oxygen consumption were unchanged. Alleviation by TxA2 receptor blockade paralleled that reported for cyclooxygenase inhibitors. Also, significant increases in coronary venous TxA2 were seen at the time of maximal increases in coronary resistance, while prostacyclin was unchanged. In summary, TxA2 appears to mediate part of the coronary constrictor effect of NPY.
These adverse effects of intracoronary papaverine have important implications in its use in patients, particularly in those in whom abnormal cardiac function already exists. Adenosine, on the other hand, seems to be without deleterious effects.
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