Regulation of postocclusive hyperemia by endogenously synthesized prostaglandins in the dog heart.

Alexander, R. Wayne; Kent, K M; Pisano, John J.; Keiser, Harry R.; Cooper, T. L.

doi:10.1172/jci108034

Cited by 119 publications

(25 citation statements)

References 26 publications

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“…In fact, PG release, confirmed by bioassay or radioimmunoassay, has been observed due to anoxia 27 and hypoxia 28 -30 in the isolated rabbit heart, and due to ischemia caused by temporary occlusion of the left main coronary artery in the perfused dog heart. 6 In all of the above experiments, however, as pointed out specifically by Block et al, 27 PG release is not concurrent with the vasodilation observed. In fact, an enhanced PG release occurs at a time when, due to the reinstitution of normal oxygen tension in the perfusate, coronary blood flow falls back toward normal.…”

Section: Discussionmentioning

confidence: 64%

Prostaglandins and the control of blood flow in the canine myocardium.

Hintze¹,

Kaley²

1977

Circulation Research

108

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SUMMARY A comprehensive study was undertaken to evaluate the effects of inhibition of prostaglandin (PG) synthesis on a variety of reactions in the coronary vascular bed of anesthetized, open-chest dogs. In 23 dogs an electromagnetic flow probe (EMFP) and hydraulic occluder were placed around either the left anterior descending or circumflex branches of the coronary artery and a needle was inserted distal to the EMFP. Injections into the coronary artery of arachidonic acid (AA), bradykinin, adenosine, angiotensin, and PGE 2 were given before and after inhibition of PG synthesis by indomethacin (IND) or meclofenamate (MF). The effects of the inhibitors on reactive hyperemia resulting from S-, 10-, 15-, and 20-second occlusions and the dilation resulting from 90-second exposure to 8% O 2 were also examined. In each experiment, inhibition of PG synthesis was ascertained by the elimination of vasodilation to AA. After administration of IND or MF, while baseline coronary blood flow was slightly reduced, the total increment of blood flow to vasodilator agents was not significantly altered. Whereas the peak dilation and volume of reactive hyperemia were decreased, the percent flow debt repaid was unchanged and total increment of coronary flow due to hypoxia-induced vasodilation was not significantly modified. Vasoconstrictor responses to angiotensin were also unchanged. These results indicate that while inhibitors of PG synthesis increase coronary resistance, they do not adversely affect vascular responsiveness. We conclude that prostaglandins play little, if any, role in modulating coronary blood flow.A NUMBER of reports assign an important role for prostaglandins in the regulation of coronary blood flow. The recent discovery that the nonsteroidal anti-inflammatory agents have in common the ability to inhibit prostaglandin (PG) synthesis' has made possible the study of the physiological role of these agents in a number of circulatory beds. The ubiquity of prostaglandins in tissues, 2 their release after pharmacological stimulation of vascular tissue, and the reduction in blood flow after the administration of inhibitors of PG synthesis 3 are all factors that support the hypothesis that prostaglandins of the E series, which are generally vasodilator, 2 are important modulators of vascular tone. Whether prostaglandins subserve this function in the coronary vascular bed, however, is still open to question.It was reported recently that prostaglandins not only are released into the myocardial circulation during episodes of hypoxia, 4 anoxia, 5 and following coronary artery occlusion 6 -7 or administration of bradykinin, 8 but also that the ensuing increase in blood flow is attenuated in the presence of PG synthesis inhibitors. Other investigators, using similar experimental techniques, have found that the inhibitors had no significant effect on the vascular responses of coronary blood vessels. 9 In view of this controversy, we undertook a comprehensive study to investigate the possible role of endogenously produced prostag...

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Section: Discussionmentioning

confidence: 64%

Prostaglandins and the control of blood flow in the canine myocardium.

Hintze¹,

Kaley²

1977

Circulation Research

108

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“…Each point is significant at P < 0.05 or P < 0.02 compared with basal. (16), we also determined the effect of trans-13-azaprostanoic acid on U46619-stimulated water flow in the presence of another inhibitor of fatty acid cyclooxygenase, meclofenamic acid, which does not inhibit cyclic nucleotide phosphodiesterase (17). At a molar concentration ratio of 300:1, trans-13-azaprostanoic acid inhibited U46619-stimulated water flow 65±6% (P < 0.02, n = 5) in meclofenamic acid (1 ,uM)-pretreated hemibladders while U46619-stimulated water flow was inhibited 64±6% in indomethacin (50,uM)-pretreated hemibladders (Fig.…”

Section: Resultsmentioning

confidence: 99%

Thromboxane and Stable Prostaglandin Endoperoxide Analogs Stimulate Water Permeability in the Toad Urinary Bladder

Burch¹,

Halushka²

1980

J. Clin. Invest.

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A B S T R A C T The effects of thromboxane B2 and the stable prostaglandin endoperoxide analogs (15Z)-hydroxy -9a -1 la -(epoxymethano)prosta -5Z,13E -dienoic acid (U44069) and (15Z)-hydroxy-1 la,9a-(epoxymethano) prosta-5Z,13E-dienoic acid (U46619) were tested on water flow across the toad urinary bladder. In the presence of indomethacin or meclofenamic acid, inhibitors of prostaglandin and thromboxane A2 synthesis, thromboxane B2 stimulated water flow in a dose-dependent manner. U44069 (1 gM) stimulated water flow from 3.6 +0.8 to 12.4+ 1.2 mg/min per 10 cm2 hemibladder surface area, while U46619 (1 ,M) stimulated water flow from 2.8± 1.0 to 21.8±2.0 mg/min per 10 cm2. The prostaglandin endoperoxide/thromboxane A2 antagonist trans-13-azaprostanoic acid, an inhibitor of vasopressin-stimulated water floy, inhibited thromboxane B2-and U46619-stimulated water flow in a dose-dependent manner. The inactive cis-13-azaprostanoic acid did not inhibit vasopressin-stimulated water flow in untreated hemibladders and had no effect on U46619-stimulated water flow in indomethacin or meclofenamic acid pretreated hemibladders. U46619 (1,M) enhanced vasopressin-stimulated water flow in indomethacin pretreated hemibladders, producing a significant parallel shift (P < 0.001) in the dose-response relationship to submaximal concentrations of vasopressin (0.1-0.6 mU/ml), while not affecting water flow stimulated by supramaximal concentrations of vasopressin (10 mU/ml). trans-13-Azaprostanoic acid abolished the potentiating effects of U46619 on vasopressin-stimulated water flow. These

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“…28-35 days later, the firm, highly vascularized, lipid-laden, subcutaneous nodules were removed with aseptic technique. The nodules were minced into 1-mm3 explants, and tissue cultures were initiated in 75-cm2 plastic flasks (20)(21)(22)(23)(24)(25) explants per flask) with the RPMI-tissue culture medium supplemented with Hepes buffer, fetal bovine serum, penicillin, and streptomycin as described above (15 ml/flask). Cultures were incubated at 37°C in a 95% air-5% CO2 atmosphere, and the tissue culture medium was changed every Characterization of the factors affecting prostaglandin biosynthesis by renal interstitial cells in tissue culture.…”

Section: Methodsmentioning

confidence: 99%

Prostaglandin biosynthesis by rabbit renomedullary interstitial cells in tissue culture. Stimulation by angiotensin II, bradykinin, and arginine vasopressin.

Zusman¹,

Keiser²

1977

J. Clin. Invest.

Self Cite

335

117

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A B S T R A C T Rabbit renomedullary interstitial cells were isolated and grown in tissue culture. These cells synthesize 0.8 ng ofprostaglandin E2 (PGE2) per microgram cellular protein per hour in monolayer tissue culture; prostaglandins A2 and F2x (PGA2 and PGF2c) biosynthesis was 10 and 5% of PGE2 biosynthesis, respectively. Arachidonic acid markedly stimulated the production of PGE2 and PGFax, with conversion rates of 0.24 and 0.02%o/h, respectively. Angiotensin II, hyperosmolality, bradykinin, and arginine vasopressin each stimulated PGE2 biosynthesis; maximum stimulation was 20, 3.7, 3.6, and 3.2 times basal production, respectively. PGE2 biosynthesis by the renomedullary interstitial cells was inhibited by isoproterenol, potassium, nonsteroidal anti-inflammatory agents (indomethacin, naproxen, ibuprofen, suprofen, meclofenamate, and acetylsalicylic acid), mepacrine (a phospholipase inhibitor), hydrocortisone, and cortisone.The rabbit renomedullary interstitial cell in tissue culture is a model system for the study of hormonal regulation of PGE2 biosynthesis. (6)(7)(8)(9). PGE has been shown to antagonize the effect of antidiuretic hormone in the toad urinary bladder (10, 11), whereas indomethacin, a potent prostaglandin synthetase inhibitor, potentiates antidiuretic hormone in in vitro and in vivo studies (12-14).The renal medullary interstitial cell is the major site of prostaglandin biosynthesis within the kidney (15). These highly specialized cells exist in high density in the renal medulla and papilla (16,17), and contain large amounts of arachidonic acid, the precursor of PGE2 biosynthesis (18).To study the production of prostaglandins by renal interstitial cells independent of the many interlocking systems which characterize renal function, we have grown rabbit renal interstitial cells in tissue culture. The rabbit renomedullary interstitial cell in tissue culture is a model system for the study of the molecular events associated with hormonal stimulation of PGE2 biosynthesis. The characterization of prostaglandin production by these cells and the effects of a number of vasoactive peptides, hormones, physiologic stimuli, and drugs on PGE2 biosynthesis comprise this investigation. Effect of cellular growth on PGA, PGE, and PGF biosynthesis by rabbit renal interstitial cells in tissue culture. Trypsin-dispersed cells from 75-cm2 flasks were pooled and replicate 25-cm2 flasks containing 5 ml of fresh tissue culture medium were inoculated. Tissue culture medium was changed at 24-h intervals. At each 24-h interval, two flasks were scraped to remove the cells from the plastic surface, and the cellular protein was determined by the method of Lowry et al. (23), with bovine serum albumin as the standard. METHODSCharacterization of the factors affecting prostaglandin biosynthesis by renal interstitial cells in tissue culture. Before the study of the effects of vasoactive substances and prostaglandin synthesis inhibitors on prostaglandin biosynthesis, the effects of osmolality, time of incubation, sodium, ...

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Regulation of postocclusive hyperemia by endogenously synthesized prostaglandins in the dog heart.

Cited by 119 publications

References 26 publications

Prostaglandins and the control of blood flow in the canine myocardium.

Prostaglandins and the control of blood flow in the canine myocardium.

Thromboxane and Stable Prostaglandin Endoperoxide Analogs Stimulate Water Permeability in the Toad Urinary Bladder

Prostaglandin biosynthesis by rabbit renomedullary interstitial cells in tissue culture. Stimulation by angiotensin II, bradykinin, and arginine vasopressin.

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