Biomedical subjects

K K Awasthi

Publications and source records attributed to K K Awasthi.

9 recordsLinked to original sources

PubMed1983

Separation and quantitative determination of radiolabeled prostaglandins, thromboxanes, 6-keto-prostaglandin F1 alpha and other arachidonic acid metabolites produced in biological material.

Evaluation of several thin-layer chromatographic procedures for the separation of various labeled arachidonic acid metabolites (including 6-keto-prostaglandin F1 alpha) produced in the biological system is described. Manual scanning and autoradiography of the plates developed by two-dimensional thin-layer chromatography was also done for locating the radioactivities due to arachidonic acid metabolites other than thromboxane B2 and the classical prostaglandins (PGF2 alpha, PGE2, and PGD2).

6-Ketoprostaglandin F1 alpha↗

PubMed1983

In vitro effect of unsaturated fatty acids on the balance between thromboxane A2 and prostacyclin in the blood vascular system.

Unsaturated fatty acids (FAs) (oleic, linoleic, alpha -linolenic, and gamma -linolenic acids) were found to inhibit platelet thromboxane synthetase. This conclusion was based on the following experimental evidence. 1. Reduced formation of TxB2 and increased formation of prostaglandins F2 alpha, E2 and D2 as seen in autoradiography of TLC plate. 2. Inhibition of ADP- and collagen-induced aggregation of PRP samples in the presence of the unsaturated FAs. 3. Reduced formation of TxB2 determined by RIA in PRP samples pretreated with the unsaturated FAs followed by collagen-induced aggregation. 4. Reduced formation of MDA in the presence of the unsaturated FAs. 5. Increased formation of PGI2 (determined as 6-keto-PGF1 alpha), PGE2, PGF2 alpha and PGD2 (redirection effect) in the presence of the unsaturated FAs in a system consisting of washed human platelet preparation and a piece of rat aorta from labelled arachidonate. TxB2 was reduced. 6. Aggregation experiment confirming above.

Animals↗

PubMed1983

Arachidonic acid metabolism in isolated aorta and lung of the rat: effects of dipyridamole, nifedipine, propranolol, hydralazine and verapamil.

Effects of some vasodilating (dipyridamole, nifedipine and verapamil) and antihypertensive (propranolol, hydralazine) drugs on arachidonic acid metabolism in isolated rat aorta and lung have been studied. Dipyridamole significantly increased the formation of PGI2 in aorta and lung. Nifedipine and verapamil decreased the formation of PGI2 in aorta, these drugs though significantly increased the formation of PGI2 in lung. Nifedipine showed no appreciable effect on the generation of TxA2 in rat aorta but in lung both nifedipine and verapamil reduced TxA2 formation though significantly only in the latter case. Dipyridamole showed no effect. The beneficial effect of dipyridamole, seems, at least in part, to be due to its ability to enhance the production of PGI2 both in the aorta and lung, and probably in other tissues as well. Nifedipine and verapamil may show their antianginal effect by a combined effect of enhanced PGI2 and reduced TxA2 formation in lung. In lung, whereas hydralazine reduced the formation of both PGI2 and TxA2, propranolol increased the formation of PGI2. Hydralazine reduced the formation of TxA2 and increased PGI2 formation in aorta. The effect of the drugs on the ability of rat aorta to inhibit collagen induced platelet aggregation of human blood platelets was also examined.

Animals↗

PubMed1983

Unsaturated fatty acids and platelet aggregation: in vitro study.

The effects of several cis and two trans fatty acids (elaidic and linoelaidic acids) - sodium salt and also in free acid form - on ADP-induced platelet aggregation were studied. The effects of the cis and trans fatty acids (sod. salt) on collagen-induced aggregation were also examined. Besides, the effects of several cis fatty acids, including dihomo-gamma-linolenic acid, on arachidonic acid induced aggregation were examined. The results indicate that unsaturated fatty acids inhibit platelet aggregation induced by ADP and collagen. The unsaturated fatty acids, however, with most blood samples did not show any antiaggregation effect on arachidonic acid-induced aggregation. While showing an antiaggregation effect on collagen-induced aggregation and failing to do so on arachidonic acid-induced aggregation, this difference in the behaviour of the unsaturated fatty acids in the two aggregations can be explained on the basis of binding of exogenous test fatty acids to plasma proteins. The mechanism(s) by which unsaturated fatty acids, in general, may exert their antiaggregation effect is discussed.

Adenosine Diphosphate↗

PubMed1983

Effects of labetalol on the arachidonic acid metabolism in human blood platelets, and in lung and aorta of the rat.

Effects of labetalol on the arachidonic acid metabolism in washed human blood platelets, and in lung and aorta of the rat was studied. Effects of this drug on the aggregation induced by usual aggregation agents, and on the prostacyclin generating capacity of rat aorta as assessed by its antiaggregation effect were also studied. The following results were obtained. 1. Reduced generation of thromboxane and HHT in platelets was observed at 1 mM conc. of the drug. 2. This drug inhibited ADP-, collagen-, and epinephrine-induced aggregation in a dose dependent manner. 3. Arachidonate-induced aggregation was only slightly inhibited at 1 mM conc. of labetalol. 4. Aorta and lung synthesized more prostacyclin in its presence from exogenous labelled arachidonate. 5. Aorta synthesized more prostacyclin from its endogenous AA pool in the presence of labetalol as assessed by inhibition of platelet aggregation.

Animals↗

PubMed1982

Effect of furosemide on the in vitro prostaglandin biosynthesis in human platelets.

Effect of furosemide at various concentrations (0.05-4 mM) was examined on the in vitro biosynthesis of prostaglandins in human platelets. At lower furosemide concentrations (0.05 and 0.1 mM) no effect was observed. At 1 and 2 mM concentrations, PGE2 significantly (P less than 0.01) increased. At 3 and 4 mM concentrations PGE2 increased though not significantly probably because of the small number of samples (n=5). A decrease in PGD2 formation was noted at 1-4 mM furosemide concentrations, though significantly only at 3 mM conc. At 1 and 2 mM concentrations, TxB2 and HHT increased whereas at 3 and 4 mM concentrations these metabolites were decreased. These effects were, however, not significant. No effect was observed on endoperoxide generation at 1 and 2 mM conc. Furosemide at 1 and 2 mM concentrations inhibited ADP- and arachidonic acid induced platelet aggregation. An increased platelet formation of PGE2 in the presence of furosemide may point to the fact that this drug shows its effect mainly on the formation of PGE2 which has been found to exert a profound effect on renal blood flow and thus ameliorates some forms of hypertension.

Arachidonic Acid↗

PubMed1982

A comparative study on the effect of cis (oleic, linoleic) and trans (elaidic, linoelaidic) fatty acids on the in vitro prostaglandin biosynthesis in human blood platelets from (1-14C) arachidonic acid.

Dietary fatty acids affect the synthesis and thus ultimate availability of prostaglandin precursors. During processing of edible fats a significant portion of the naturally occurring cis fatty acids is changed to the respective trans isomers. Trans fatty acids could have a wide variety of effects including their effect on prostaglandin synthesis. A comparative study on the effect of cis (oleic and linoleic) fatty acids and their corresponding trans isomers (elaidic and linoelaidic acids) on the in vitro prostaglandin biosynthesis in human blood platelets was made. Linoleic acid (0.5, 1.0 mM) showed the same effect on the various arachidonic acid (AA) metabolites as reported earlier by us, that is, increased generation of prostaglandins and thromboxanes and reduced amounts of HHT and HETE (26). Linoelaidic acid at these two concentrations had the same effect but to a lesser extent. Both linoleic and linoelaidic acids at 0.25 mM concentration reduced TxB2 formation. Oleic and elaidic acids (0.5, 1.0 mM) decreased the formation of TxB2 though not significantly. With oleic acid, the results in respect of other AA metabolites were similar to those reported by us earlier (26). MDA was reduced significantly in the presence of linoleic, linoelaidic and oleic acids; cis isomers being more effective. In the presence of linoleic and linoelaidic acids, prostaglandin endoperoxides were reduced significantly; there was no change in the presence of oleic and elaidic acids. Thus fatty acids seem to affect the platelet cyclo-oxygenase activity; this being more pronounced in the case of cis fatty acids compared to their trans isomers. Reduction in cyclo-oxygenase activity also depends upon the number of double bonds in the acids.

Arachidonic Acids↗

PubMed1982

Effect of some saturated and unsaturated fatty acids on prostaglandin biosynthesis in washed human blood platelets from (1-14 C)arachidonic acid.

The effects of some saturated (lauric, palmitic and stearic) an unsaturated (linoleic, gamma-linolenic, alpha-linolenic and oleic) fatty acids at 0.1. 0.25 and 0.5 mM concentrations on the in vitro metabolization of (1-14 C) arachidonic acid by washed human blood platelets have been studied. Effects of these fatty acids were studied with intact as well as lysed platelet preparations. With intact platelet preparations it was found that (i) all unsaturated fatty acids enhanced the biosynthesis of TxB2, PGE2, PGD2 and PGF2 alpha, (ii) unsaturated fatty acids reduced the formation of HHT and HETE with the exception of oleic acid which showed very little effect, (iii) unsaturated fatty acids reduced the formation of MDA, whereas palmitic and stearic acids increased its formation and (iv) all unsaturated fatty acids reduced the synthesis of prostaglandin endoperoxides. These results support our previous observations where effects of fatty acids were examined at higher concentrations (10). At 0.1 mM FA concentration, inconsistent results were obtained. With lysed platelet preparations all cyclooxygenase products were reduced in presence of unsaturated fatty acids, whereas HETE formation was reduced only in presence of linoleic and gamma-linolenic acids. Electron micrographs of washed platelet suspensions were obtained with untreated platelet preparations and platelet preparations treated with 0.25 and 0.5 mM linoleic acid concentrations. The results are discussed in the light of a possible soap-like effect of FA salt on platelets.

Arachidonic Acids↗

PubMed1982

Effect of some vasodilating and antihypertensive drugs on the in vitro biosynthesis of prostaglandins from (1-14C) arachidonic acid in washed human blood platelets.

Effects of some vasodilating (oxyfedrine, dipyridamole, verapamil and nifedipine) and antihypertensive (propranolol, hydralazine, prazosin and dihydralazine) drugs on the human blood platelet biosynthesis of prostaglandins from labelled arachidonic acid have been examined in vitro. Malondialdehyde (MDA) production in platelets and their aggregation in presence of these drugs were also studied. All the drugs inhibited the generation of thromboxane A2 which correlated well with the reduced platelet formation of MDA in presence of several of these drugs. In case of seven of the eight drugs, separation of HHT from HETE could be made. Values of these metabolites - especially those of HHT were found to be reduced, thus supporting the MDA and TxA2 data. With several of these drugs, ADP-induced platelet aggregation was inhibited either completely or partially. The results show that the well-known completely or partially. The results show that the well-known effects of these drugs might well be augmented by their effect on the platelet metabolism of arachidonic acid.

Antihypertensive Agents↗