Vascular Actions of Frusemide and Bumetanide on the Rat Superior Mesenteric Vascular Bed: Interactions with Prostaglandins

1976 ◽  
Vol 51 (s3) ◽  
pp. 257s-258s
Author(s):  
D. F. Horrobin ◽  
M. S. Manku ◽  
J. P. Mtabaji
Keyword(s):  
Prostaglandin E2 ◽  
Inhibitory Effect ◽  
Prostaglandin Synthesis ◽  
Inhibitory Effects ◽  
Perfusion Fluid ◽  
Endogenous Prostaglandin ◽  
Vascular Bed ◽  
Mesenteric Vascular Bed

1. The addition of frusemide or bumetanide to perfusion fluid inhibited the response of the isolated mesenteric vascular bed to noradrenaline. 2. Addition of prostaglandin E2 to the perfusion fluid completely restored the response to noradrenaline. 3. Inhibition of prostaglandin secretion by indomethacin with restoration of responses to noradrenaline by the addition of exogenous prostaglandin E2 prevented the inhibitory effect of frusemide or bumetanide on responses to noradrenaline. 4. The inhibitory effects of diuretics on responsiveness to noradrenaline is mediated by blockade of endogenous prostaglandin synthesis.

Potentiation of Pressor Effects of Noradrenaline and Potassium Ions in the Rat Mesenteric Arteries by Physiological Concentrations of Angiotensin II: Effects of Prostaglandin E2 and Cortisol

1977 ◽  
Vol 53 (3) ◽  
pp. 233-239 ◽  
Author(s):  
K. Kondo ◽  
M. S. Manku ◽  
D. F. Horrobin ◽  
R. Boucher ◽  
J. Genest
Keyword(s):  
Angiotensin Ii ◽  
Prostaglandin E2 ◽  
Potassium Chloride ◽  
Prostaglandin Synthesis ◽  
Mesenteric Arteries ◽  
Potassium Ions ◽  
Vascular Bed ◽  
Vasoconstrictor Response ◽  
Mesenteric Vascular Bed

1. In the perfused rat mesenteric vascular bed, the effects of angiotensin II, cortisol and prostaglandin E2 on the vascular responses to noradrenaline or potassium chloride were studied. 2. Angiotensin II in subpressor concentrations potentiated the vasoconstrictor response to noradrenaline and potassium chloride. This effect of angiotensin II was inhibited in the presence of indomethacin and prostaglandin E2. 3. Cortisol in physiological concentrations inhibited the potentiating effect of angiotensin II. 4. Prostaglandin E2 enhanced the vasoconstrictor response to noradrenaline. This effect was not abolished by cortisol. 5. These results suggest that some actions of angiotensin II and cortisol in vivo are mediated by the regulation of prostaglandin synthesis or release.

Inhibitory effects of DuP 753 and EXP3174 on responses to angiotensin II in pulmonary vascular bed of the cat

1992 ◽  
Vol 73 (5) ◽  
pp. 2054-2061 ◽  
Author(s):  
T. J. McMahon ◽  
A. D. Kaye ◽  
J. S. Hood ◽  
R. K. Minkes ◽  
B. D. Nossaman ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Dose Response ◽  
Inhibitory Effect ◽  
Response Relationship ◽  
Norepinephrine Release ◽  
Inhibitory Effects ◽  
Dose Response Relationship ◽  
Vascular Bed ◽  
The Right ◽  
Pulmonary Vascular Bed

The effects of the non-peptide antagonist DuP 753 and its metabolite EXP3174 on responses to angiotensin II were investigated in the pulmonary vascular bed of the intact-chest cat. Under conditions of controlled blood flow and constant left atrial pressure, injections of angiotensin II into the perfused lobar artery caused dose-related increases in lobar arterial pressure. Responses to angiotensin II were reproducible and were not changed by meclofenamate or prazosin, indicating that prostaglandin or norepinephrine release does not mediate or modulate pulmonary vascular responses to the peptide. DuP 753 (1–5 mg/kg iv) decreased responses to angiotensin II in a competitive manner, and the duration of the blockade was related to dose of the antagonist. DuP 753 had no significant effect on responses to U-46619, norepinephrine, serotonin, endothelin-1, vasopressin, or BAY K 8644. EXP3174 also decreased responses to angiotensin II without altering responses to agents that act by a variety of mechanisms. The inhibitory effect of EXP3174 (1 mg/kg iv) was not overcome by angiotensin II in the range of doses studied, and the shift to the right of the dose-response curve was nonparallel, suggesting that the blockade was noncompetitive. The blockade was long in duration, and, when the dose of EXP3174 was decreased to 0.1 mg/kg iv, the blockade was surmounted and the shift to the right of the dose-response relationship was parallel. DuP 753 and EXP3174 had little effect on mean baseline pressures in the cat.(ABSTRACT TRUNCATED AT 250 WORDS)

Differential effects of L-N5-(1-iminoethyl)-ornithine on tone and endothelium-dependent vasodilator responses

1997 ◽  
Vol 273 (3) ◽  
pp. L588-L594 ◽  
Author(s):  
B. J. DeWitt ◽  
H. C. Champion ◽  
J. R. Marrone ◽  
D. B. McNamara ◽  
T. D. Giles ◽  
...  
Keyword(s):  
Methyl Ester ◽  
Substance P ◽  
Arterial Pressure ◽  
Inhibitory Effect ◽  
Benzyl Ester ◽  
Inhibitory Effects ◽  
Synthesis Inhibitor ◽  
Vascular Bed ◽  
Pulmonary Vasodilator ◽  
Pulmonary Vascular Bed

The effects of the nitric oxide (NO) synthesis inhibitor L-N5-(1-iminoethyl)-ornithine (L-NIO) on baseline tone and on responses to the endothelium-dependent vasodilator agents were investigated in the pulmonary vascular bed of the cat under constant-flow conditions. When administered in doses of 1 and 5 mg/kg i.v., L-NIO inhibited pulmonary vasodilator responses to acetylcholine, bradykinin, and substance P but did not alter vasodilator responses to adenosine, pinacidil, or adrenomedullin. L-NIO in doses of 1-10 mg/kg i.v. did not significantly affect baseline lobar arterial pressure, and when administered in doses of 10-30 mg/kg i.v. the inhibitory effect on responses to bradykinin and substance P was not greater than that observed when the lower doses of L-NIO were administered. L-NIO in doses of 5-30 mg/kg i.v. reduced plasma reactive nitrogen intermediate levels. The inhibitory effects of L-NIO were similar to the inhibitory effects of N omega-nitro-L-arginine, N omega-nitro-L-arginine methyl ester, and N omega-nitro-L-arginine benzyl ester. The highest dose of L-NIO studied (30 mg/kg i.v.) caused a significant increased in lobar arterial pressure, and the administration of N omega-nitro-L-arginine methyl ester (100 mg/kg i.v.) caused a significant increase in lobar arterial pressure in animals previously treated with L-NIO (1 mg/kg i.v.). The results of the present study show that the effects of L-NIO on endothelium-dependent vasodilator responses and on baseline tone can be separated and may be interpreted to suggest that basal release of NO does not play an important role in the maintenance of baseline tone in the pulmonary vascular bed of the cat.

scholarly journals The interaction between lipid peroxidation and prostaglandin synthesis in rabbit kidney-medulla slices

1983 ◽  
Vol 212 (1) ◽  
pp. 167-171 ◽  
Author(s):  
Y Fujimoto ◽  
H Tanioka ◽  
I Keshi ◽  
T Fujita
Keyword(s):  
Lipid Peroxidation ◽  
Ascorbic Acid ◽  
Arachidonic Acid ◽  
Prostaglandin E2 ◽  
Inhibitory Effect ◽  
Prostaglandin Synthesis ◽  
Rabbit Kidney ◽  
Kidney Medulla ◽  
Prostaglandin Endoperoxide Synthase ◽  
Generating System

Lipid peroxidation induced by ascorbic acid and Fe2+ was inhibited by mepacrine (phospholipase A2 inhibitor) and aspirin (prostaglandin cyclo-oxygenase inhibitor) in rabbit kidney-medulla slices. Moreover, ascorbic acid and Fe2+ potentiated the inhibitory effect on prostaglandin E2 formation by mepacrine, but they had no influence on prostaglandin E2 production decreased by aspirin. Lipid peroxidation induced by ascorbic acid and Fe2+ appears to be affecting the activity of prostaglandin endoperoxide synthase. These results suggest that lipid peroxidation is connected closely with the prostaglandin-generating system, and it has the potential to modulate the turnover of arachidonic acid and prostaglandin synthesis.

Effects of insulin, adenosine, and prostaglandin on alpha-adrenergic-stimulated respiration in brown adipocytes

1986 ◽  
Vol 250 (5) ◽  
pp. C738-C743 ◽  
Author(s):  
R. J. Schimmel ◽  
L. McCarthy
Keyword(s):  
Adenylate Cyclase ◽  
Prostaglandin E2 ◽  
Pertussis Toxin ◽  
Mode Of Action ◽  
Inhibitory Effect ◽  
Inhibitory Effects ◽  
Brown Adipocytes

The present study compared the effects of insulin, 2-chloroadenosine, and prostaglandin E2 as inhibitors of respiration in hamster brown adipocytes stimulated with either isoproterenol or phenylephrine. Addition of 2-chloroadenosine or prostaglandin E2 strongly antagonized isoproterenol-stimulated respiration; phenylephrine-stimulated respiration was also partially inhibited by 2-chloroadenosine and prostaglandin E2, but the extent of inhibition caused by these agents was not as great as when isoproterenol was used. Isoproterenol-stimulated respiration was inhibited by insulin, but phenylephrine-stimulated respiration was insensitive to the inhibitory effect of insulin. When brown adipocytes were pretreated with pertussis toxin, isoproterenol-stimulated respiration was enhanced, but phenylephrine-stimulated respiration was not significantly affected. The inhibitory effects of 2-chloroadenosine and prostaglandin E2 on isoproterenol-stimulated respiration were completely blocked by pertussis toxin, indicating that the mode of action of these inhibitory hormones was secondary to inhibition of adenylate cyclase and resultant inhibition of lipolysis. Prostaglandin E2 inhibition of phenylephrine-stimulated respiration was also abolished by pertussis toxin. In contrast, 2-chloroadenosine inhibition of phenylephrine-stimulated respiration persisted in adipocytes treated with pertussis toxin. These data suggest that phenylephrine stimulates respiration through a mechanism that is not altered by pertussis toxin and further that 2-chloroadenosine inhibition of isoproterenol- or phenylephrine-stimulated respiration can be dissociated.

Effects of potassium and ouabain on the vascular reactivity to norepinephrine in the rat mesenteric artery

1979 ◽  
Vol 57 (8) ◽  
pp. 908-912 ◽  
Author(s):  
Kazuoki Kondo ◽  
Tetsuji Okuno ◽  
Konosuke Konishi ◽  
Takao Saruta ◽  
Eiichi Kato
Keyword(s):  
Prostaglandin E2 ◽  
Mesenteric Artery ◽  
Vascular Reactivity ◽  
Potassium Concentration ◽  
Vascular Wall ◽  
Vascular Response ◽  
Vascular Bed ◽  
Rat Mesenteric Artery ◽  
Low Potassium ◽  
Mesenteric Vascular Bed

In the perfused rat mesenteric vascular bed, the effects of potassium and ouabain on the vascular response to norepinephrine were studied. Neither changing the concentration of potassium (1.9 to 7.9 mM) nor adding ouabain (8.6 × 10−7 to 2.2 × 10−4 M) to the perfusate changed the basal pressure. A slight increase in the potassium concentration in the perfusate attenuated the vascular response to norepinephrine, and a slight decrease in the potassium concentration potentiated this response. Ouabain in the perfusate potentiated the vascular response to norepinephrine in a dose-related manner. The effect of potassium on the vascular response was inhibited in the presence of ouabain. In preparations in which vascular reactivity had been abolished by indomethacin and then restored by prostaglandin E2, the effects of potassium and ouabain on the vascular reactivity to norepinephrine were similar to those found in the untreated preparations. These results indicate that a slight change in potassium concentration in the perfusate can affect the vascular response to norepinephrine by changing the activity of a Na+–K+-dependent ATPase. It is also suggested that the potentiating effect of low potassium concentration on the norepinephrine response is, at least in the rat mesenteric vascular bed, not mediated by the synthesis of prostaglandin E2 in the vascular wall.

The influence of phenelzine and tranylcypromine on the release of prostaglandins from the rat mesenteric vascular bed

1988 ◽  
Vol 66 (9) ◽  
pp. 1206-1209 ◽  
Author(s):  
Bassam A. Nassar ◽  
Yung-Sheng Huang ◽  
Alan T. J. McDonald ◽  
Kenneth D. Jenkins ◽  
David F. Horrobin
Keyword(s):  
Arachidonic Acid ◽  
Linolenic Acid ◽  
Inhibitory Effect ◽  
Prostaglandin E ◽  
Low Doses ◽  
Vascular Bed ◽  
Mesenteric Vascular Bed

We investigated the effects of phenelzine and tranylcypromine on the release of prostacyclin, thromboxane A2, prostaglandin E2, and prostaglandin E1 from the isolated perfused rat mesenteric vascular bed. Perfusion of the preparation with phenelzine in concentrations of 15, 45, and 135 μM for 150 min led to attenuated release of all four prostaglandins measured. Inhibition generally occurred with the lowest dose used and was most prominent with the highest concentration. Tranylcypromine also decreased prostaglandin formation. However, low doses were not effective in the suppression of prostacyclin release. Both drugs had an inhibitory effect on production of prostaglandin E1, which is a metabolite of dihomo-γ-linolenic acid, the precursor of arachidonic acid, but this was only shown to be significant with phenelzine. In this work we demonstrate that phenelzine and tranylcypromine have an inhibitory effect on the production of 2-series prostaglandins derived from arachidonic acid, and possibly a similar effect on prostaglandins of the 1-series derived from dihomo-γ-linolenic acid.

Vascular actions of furosemide and bumetanide on the rat superior mesenteric vascular bed: interactions with prolactin and prostaglandins

1976 ◽  
Vol 54 (3) ◽  
pp. 357-366 ◽  
Author(s):  
J. P. Mtabaji ◽  
M. S. Manku ◽  
D. F. Horrobin
Keyword(s):  
Pressor Response ◽  
Prostaglandin Synthesis ◽  
Prostaglandin E ◽  
Vascular Effects ◽  
Adequate Amount ◽  
Vascular Bed ◽  
Pressor Responses ◽  
Mesenteric Vascular Bed ◽  
Ovine Prolactin

The mesenteric vascular bed of the rat was used to investigate the effects of furosemide, bumetanide, prolactin, aspirin, indomethacin and prostaglandin E2 on the pressor response to norepinephrine. Furosemide, bumetanide and indomethacin could all inhibit the responses to norepinephrine: in each case responsiveness was restored by the addition of prostaglandin E2 to the perfusate. Bumetanide and furosemide both failed to inhibit responsiveness in the presence of an adequate amount (50 pg/ml) of prostaglandin E2. As has been shown previously, ovine prolactin in a concentration of 50 ng/ml enhanced pressor responses to norepinephrine while 500 ng/ml, after an initial potentiation, inhibited responsiveness. Aspirin, furosemide and bumetanide all reversed both the potentiation produced by the lower prolactin concentration and the inhibition produced by the higher one. When taken in conjunction with other evidence these results suggest that the diuretics exert their vascular effects by inhibiting prostaglandin synthesis whereas prolactin acts by stimulating such synthesis.

Itanoxone, An Inhibitor Of Cyclo-Oxygenase, Acts Preferentially On Platelet Than On Vascular Enzyme

1981 ◽  
Author(s):  
S Villa ◽  
A DeLhon ◽  
C Palmier ◽  
M Livio ◽  
B Maynardier ◽  
...  
Keyword(s):  
Competitive Inhibition ◽  
Cumulative Effect ◽  
Inhibitory Effect ◽  
Prostaglandin Synthesis ◽  
Measurable Effect ◽  
Inhibitory Effects ◽  
Antithrombotic Drug ◽  
Repeated Doses ◽  
Dose Dependent ◽  
Potential Use

Several attaints have been made to dissociate the inhibitory effects of aspirin on platelet and vascular cells, but no definite results have been obtained. Other drugs, presumably acting on cyclo-oxygenase, are therefore being investigated for their relative inhibitory effect on platelet and vascular prostaglandin synthesis.The present study was performed in male CD-COBS rats. Itanoxone [ (chloro-2' -diphenyl) -4-oxo-4 methylene 2-butyric acid ], a newly developed, hypolipidemic and hypouricemic compound with moderate anti-inflanmatory activity, showed a short lived, dose dependent (20-200 mg/kg, orally) apparently competitive inhibition of platelet MDA stimulated by either thrombin or arachidonic acid. Repeated doses did not result in any cumulative effect. At doses which completely blocked MDA production, itanoxone also inhibited thrombin-stimulated thromboxane B2 production in platelets but had no measurable effect on vascular prostacyclin generation measured both by a bioassay and a radioimmunoassay of its stable derivative 6-Keto-PGF1α . Pretreatment with itanoxone partially prevented therrhibitory effect of aspirin on both platelet and vascular prostaglandin synthesis. This suggests that itanoxone - like aspirin - acts at the level of cyclo-oxygenase but has much greater selectivity on the platelet enzyme.This pharmacological activity is of great theoretical interest for potential use of this compound as an antithrombotic drug.

Sign in / Sign up

Export Citation Format

Share Document