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Biomedical subjects

G Kaley

Publications and source records attributed to G Kaley.

At least 91 records · Page 5Linked to original sources
PubMed1988

Microcirculatory effects of leukotrienes, LTC4 and LTD4, in rat cremaster muscle.

Studies were performed to determine the vasomotor effects of leukotrienes, LTC4 and LTD4, on rat cremaster third-order arterioles and the effects of PGE2 on arteriolar responsiveness to LTC4. Five to six week-old male rats were anesthetized with sodium pentobarbital (35 mg/kg) and the left cremaster muscle exteriorized and prepared for in vivo television microscopy. Measurement of changes in arteriolar internal diameters was performed with an electronic image shearing device under control conditions and during the topical administration of vasoactive substances before and after the suffusion, onto the surface of the cremaster muscle, of either indomethacin (IND, 10 ug/ml) or 5,8,11,14-eicosatetraynoic acid (ETYA, 20 ug/ml). LTC4 and LTD4 were found to evoke equivalent, dose-dependent arteriolar constrictions, in the dose range of 2 pg to 2 ng, and concomitant decreases in microvascular blood flow. The application of either IND or ETYA, to the cremaster muscle did not significantly effect control diameters nor the constrictor responses to leukotrienes. While the principal action of the two leukotrienes was vasoconstriction, small dilator responses were occasionally observed that were also not affected by IND or ETYA. PGE2 did not inhibit the arteriolar constrictor responses to LTC4. The current observations indicate that LTC4 and LTD4 are extremely potent arteriolar constrictor agents in skeletal muscle and that their vascular effects are not mediated or modulated by products of the cyclooxygenase or lipoxygenase pathway of arachidonic acid metabolism.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1987

Oxygen metabolites and vasodilator mechanisms in rat cremasteric arterioles.

The effects of oxygen metabolites (superoxide anion and hydrogen peroxide) on male Wistar rat cremasteric arterioles and the involvement of these species in the mechanism of vasodilation to arachidonic acid and bradykinin were examined by in vivo television microscopy. In the present study, xanthine oxidase-derived oxygen metabolites from endogenous substrates elicited vasodilation that was selectively and almost completely inhibited by catalase but not by superoxide dismutase. These findings implicate hydrogen peroxide as the vasoactive metabolite generated. Topical application of hydrogen peroxide itself on cremasteric arterioles caused concentration-dependent dilation over the range of 10(-7) to 10(-4) M. Responses to hydrogen peroxide concentrations of up to 10(-5) M were completely inhibited by indomethacin, suggesting that hydrogen peroxide-induced increases in vessel diameter are primarily mediated through the production of vasodilator prostaglandins. In this study, we have not found any evidence to suggest that dilator responses to arachidonic acid or bradykinin are mediated through the extracellular generation of oxygen metabolites. Hydrogen peroxide-induced vasodilation might be involved in the events linking the sensing of oxygen tension through intracellular peroxide formation to the production of vasoactive mediators in the cremasteric microcirculation.

Animals↗
PubMed1986

Prostaglandins modulate baroreflex-induced changes in blood pressure and myocardial function in anesthetized dogs.

The purpose of our study was to investigate the role of prostaglandins in the changes in myocardial function and peripheral and coronary vascular resistance which accompany a generalized increase in sympathetic tone caused by carotid baroreflex unloading in the anesthetized dog. Bilateral carotid artery occlusion (BCO) with heart rate held constant by electrical pacing (150 beats/min) resulted in increases in systolic, (33%) diastolic (40%), and mean (35%) arterial pressures, LV systolic pressure (33%) and left ventricular (LV) dP/dt (37%). After blockade of prostaglandin synthesis with indomethacin (N = 11) or meclofenamate (N = 6) the increases in systolic (41%), diastolic (45%), and mean (41%) arterial pressures, LV systolic pressure (39%), LV dP/dt (52%), and cardiac work caused by BCO were significantly greater, in spite of the initially higher baseline values (11-18%) following the administration of the drugs. In contrast, the changes in circumflex coronary blood flow and coronary vascular resistance to BCO were essentially the same before and after inhibition of prostaglandin synthesis. Systemic prostaglandin synthesis may, therefore, play a significant role in the control of systemic arterial pressure and myocardial function, most probably by modulating the release of norepinephrine from adrenergic nerve terminals, without adversely affecting coronary blood flow regulation.

Animals↗
PubMed1986

Prostaglandins participate in the renal vasodilation due to hydralazine in dogs.

The authors studied the effects of bolus injections of hydralazine (500 micrograms) into the renal artery of chloralose-anesthetized dogs. In control dogs, hydralazine injection resulted in an increase in renal artery blood flow of 110 +/- 10.4 ml/min (53 +/- 4.7%) from 214 +/- 28 ml/min. In dogs that were pretreated with the alpha-1 adrenergic antagonist, prazosin (1 mg/kg), hydralazine injection increased renal blood flow by 95 +/- 22 ml/min (37 +/- 7.4%) from 253 +/- 19 ml/min, an increase not different from that found in control dogs. However, in dogs pretreated with indomethacin (5 mg/kg) or sodium meclofenamate (3 mg/kg), inhibitors of cyclooxygenase, hydralazine injection resulted in an increase in renal artery blood flow of only 44 +/- 5.3 ml/min (19 +/- 2.7%) from 235 +/- 23 ml/min, an increase significantly different from that in control dogs (P less than .05). The renal blood flow response to hydralazine injection developed slowly, reached a maximum in 20 min and was maintained for at least 1 hr. Arterial blood pressure, heart rate and descending aortic blood flow were not significantly changed after hydralazine injection. The authors conclude that hydralazine increases renal blood flow in dogs by a mechanism independent of alpha-1 adrenergic receptors and that this increase is, in large part, mediated by prostaglandin release.

Animals↗
PubMed1984

Nitroglycerin and nitroprusside increase coronary blood flow in dogs by a mechanism independent of prostaglandin release.

The hypothesis that local release of vasodilator prostaglandins mediates, in part, the decrease in coronary resistance after nitroglycerin (NG) administration was tested. NG (60 micrograms/min) and nitroprusside (NP) (30 micrograms/min) were infused for 10 minutes into the left circumflex coronary artery of 9 open-chest, chloralose-anesthetized dogs before and after blockade of prostaglandin synthesis with indomethacin (5 mg/kg). Also, to eliminate the effects of reflex tachycardia on the responses to NG and NP, these experiments were repeated in 6 dogs with heart rate held constant by pacing. NG infusion into dogs without pacing resulted in a maximal increase in coronary blood flow of 55% and after 8 minutes of infusion an increase of 20%, from a baseline of 57 ml/min. NP infusion resulted in a maximal increase in blood flow of 89% and after 8 minutes an increase of 71%, from a baseline of 64 ml/min. In dogs with heart rate held constant, NG infusion caused a maximal increase in coronary artery blood flow of 132% and after 8 minutes of infusion an increase of 18%, from a baseline of 48 ml/min; NP infusion resulted in increase from 51 ml/min of 132% and 62%, respectively. In neither group of dogs did indomethacin significantly change the increases in coronary blood flow or decreases in coronary resistance to NG or NP. Thus, both NG and NP, when infused into the coronary artery of dogs, cause increases in coronary blood flow and decreases in coronary resistance by a mechanism which is independent of prostaglandin release.

Animals↗
PubMed1984

Mechanisms of reflex bradycardia and hypotension by metabolites of arachidonic acid in the cat.

In the cat, intravenous injections of arachidonic acid or prostaglandin (PG)F2 alpha caused significant reductions in mean arterial pressure and heart rate which were eliminated or significantly lessened, respectively, by previous administration of indomethacin. The bradycardia to intravenous prostacyclin (PGI2) was unaffected by indomethacin. In cats with bilateral ligation of the carotid arteries to eliminate competition between systemic baroreflexes and cardiopulmonary reflexes, PGI2, PGF2 alpha and arachidonic acid caused significantly greater hypotension and bradycardia than in cats with intact carotid baroreflexes. The bradycardia to PGI2, PGF2 alpha and arachidonic acid was eliminated by bilateral vagal section or atropine. PGE1, PGE2 and nitroprusside caused dose-related falls in mean arterial pressure and a small tachycardia. In a small group of cats (7 of 67) nitroprusside also caused a reduction in heart rate which was eliminated by indomethacin. We conclude that the reflex bradycardia to PGF2 alpha, like that to arachidonic acid is, at least in part, the result of the stimulation of synthesis of another prostaglandin, most likely PGI2.

Animals↗
PubMed1984

Ventricular receptors activated following myocardial prostaglandin synthesis initiate reflex hypotension, reduction in heart rate, and redistribution of cardiac output in the dog.

Arachidonic acid (250 micrograms) injected into the left circumflex coronary artery of anesthetized dogs, with carotid arteries tied to reduce baroreflex-induced changes, caused a reduction in heart rate (-15 +/- 1.6 beats/min), mean arterial pressure (-27 +/- 3.4 mm Hg), and left ventricular dP/dt (-939 +/- 138 mm Hg/sec). In contrast, injection of arachidonic acid into the left anterior descending coronary artery caused smaller changes in heart rate (-4.6 +/- 1.6 beats/min), arterial pressure (-14 +/- 2.8 mm Hg), and left ventricular dP/dt (-118 +/- 131 mm Hg/sec). The hypotension following the injection of arachidonic acid results from an increase in perfusion of the kidney and skeletal muscle (as measured by radioactive microspheres), and is entirely reflex, since the changes in renal blood flow, as well as the reduction in heart rate and the hypotension, are eliminated by bilateral vagal section. Increasing the dose of arachidonic acid results in dose-related changes in heart rate, arterial pressure, and left ventricular dP/dt. Prostacyclin and prostaglandin E2, the two principle coronary vasodilator metabolites of arachidonic acid, but not nitroprusside, cause a fall in blood pressure and heart rate, establishing that coronary vasodilation per se is not responsible for initiating the reflex fall in arterial pressure and heart rate. In two dogs with sinoaortic denervation, circumflex injection of arachidonic acid caused larger reductions in heart rate (-21 +/- 1.5 beats/min) and mean arterial pressure (-51 +/- 3.5 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Leukotriene D4 reduces coronary blood flow in the anesthetized dog.

We studied the effects of intracoronary administration of leukotriene (LT)D4 on coronary blood flow and myocardial function in chloralose anesthetized dogs. For comparison, the effects of injections of U-46619 were examined in the same dogs. Both LTD4 and U-46619 decreased coronary blood flow, left ventricular dP/dt and cardiac output. LTD4 was ten times more potent than U-46619 in decreasing coronary blood flow. The effects of neither drug were different after indomethacin administration.

Animals↗
PubMed1981

Prostacyclin (PGI2) mediates hypoxic relaxation of bovine coronary arterial strips.

Bovine coronary arterial strips (BCA) exhibiting spontaneous tone, relax in response to a decrease in the pO2 of the bathing medium. Experiments were performed to determine if prostaglandins (PGs) mediate the oxygen-induced changes in tension. BCA were equilibrated in Krebs-bicarbonate solution at 37 degrees C gassed with 95% O2, 5% CO2 and tension was measured isometrically. When the pO2 of the bathing medium was decreased, BCA exhibited reversible reductions in tension. Switching from 95% O2, 5% CO2 to 95% N2, 5% CO2 (anoxia) elicited an initial relaxation followed by a contraction. In contrast, a change to 5% O2, 5% CO2, 90% N2 (hypoxia) was followed by a sustained relaxation. Re-introduction of O2 to anoxic strips produced a biphasic response: relaxation followed by contraction. Indomethacin or eicosatetraynoic acid (EYA) increased tone and inhibited the relaxation produced by anoxia or hypoxia. Indomethacin or EYA did not inhibit the relaxation of anoxic strips during re-introduction of O2, but did inhibit the contraction partially. Relaxation of arterial strips to arachidonic acid (AA) was similar to relaxation to prostacyclin (PGI2). Anoxia limited the relaxation to AA but not to PGI2. We conclude that PG synthesis contributes to the basal tone and the hypoxia-induced relaxation of BCA. In addition, hypoxia, unless severe, does not prevent the conversion of AA to PGI2.

Animals↗
PubMed1980

Quantitation by bioassay of mixtures of prostaglandins E2 and I2.

A bioassay method is described for the simultaneous identification and quantitation of small amounts of prostaglandins E2 and I2. Strips of rabbit coeliac and bovine coronary arteries were suspended within a common chamber surrounded by a heated water bath. The tissues were coupled individually to transducers to record their length. Using a superfusion flow rate of 2.0 ml/min the rabbit coeliac and bovine coronary arterial strips responded in a highly reproducible manner to threshold doses of 0.1 ng PGE2 and 1.0 ng PGI2, respectively. This technique is more sensitive than the conventional bioassay methods to quantify and differentiate between prostaglandins.

Animals↗