Pharmacological Research, Vol. 25, Supplement 1, 1992

69

PROSTAGLANDINS IN RAT HEART P .BELLUCO, A .M .GAION, M .G .RICATTI, P .DORIGO and R .M .GAION Department of Pharmacology, University of Padova Largo E . Meneghetti 2, 35131 Padova, Italy

Key words : Prostaglandins, rat heart, atria, ventricles .

A tissue-specificity for the production of prostaglandins (PGs) has been reported by many authors (1) . In all these studies qualitative and quantitative differences were found after incubation of tissue homogenates and in the presence of exogenous precursors . Moreover, different regions of the same organ posses marked specificity for PG synthesis : in the heart the major sites of PGI 2 byosinthesis are the coronary vessels, whereas PGF 2a and PGE 2 are predominant PGs in non vascular regions . In the present work the release of PGs, from whole isolatad rat heart and in two different portions, i .e ., atria and ventricles was investigated . Male Wistar rats (180 ± 20 g b .w .) fed a standard laboratory diet were used for the present experiments . Rat tissues (whole heart, atria or ventricles) were placed into 9 ml Webb solution bubbled with a gas mixture (95% 0 2 and 5% C0 2 ) at a temperature of 32°C and incubated for 15 min under gentle shaking . Rat duodenum segments and aorta rings were also incubated under the same conditions in order to make a comparison among different tissues . In same experiments the preparations were allowed to equilibrate for 60 min before incubation . PGs were extracted from incubation media (PG release) and tissue samples (PG tissue content) and detected by an HPLC method as previously described (2) . The release of PGs from the whole heart during a 15 min incubation was higher for 6k PGF la (22 .3 ± 1 .7 ng/g tissue) than for PGF2a (10 .3 ± 0 .4 ng/g tissue), while PGE 2 and PGD 2 reached detectable levels only in 2 out of 4 experiments . The absolute amount of PGs released was much lower as compared to other rat tissue, i .e . aorta and duodenum (Table 1) . Moreover marked tissue-released differences were observed in the relative amounts released . In fact the 6k PGF la to PGF 2a ratios were 2 .2 for heart, 14 .5 for aorta, 0 .4 for duodenum (Table 1) . Taking into account the fact that tissue manipulation during excision and cleaning may by itself be a stimulus for PG release, in a series of experiments rat hearts were preincubated for 60 min after which they were transferred into fresh medium and further incubated for 15 min for the quantitation of PG release . Under these conditions the amounts of 6k PGF la and PGF 2a released during the 15 min incubation were 16 .4 ± 3 .0 and 3 .3 1 0 .9, respectively, indicating that an overproduction of PGs may occur immediately after manipulation of the tissue .

1043-6618/92/2510069-02/$03 .00/0

© 1992 The Italian Pharmacological Society

70

Pharmacological Research, Vol. 25, Supplement 1, 1992 Table 1 . BASAL PROSTAGLANDIN OUTPUT FROM WHOLE RAT TISSUES

TISSUE

6K PGF la

PGF 2a

HEART

22 .3±1 .7

10 .3±0 .4

DUODENUM

69 .6±7 .2

158 .4±11 .9

1084 .3±203 .1

75 .0±4 .9

AORTA

PGE2

< 1

PGD2

6K PGF la/ PGF 2a

< 1

2 .2

24 .5±3 .5

71 .0±8 .2

0 .4

76 .916 .3

39 .3±4 .5

14 .5

Results are means (± S .E .) of 4 experiments for heart and of 3 experiments for aorta and duodenum, and are given as ng/g/15 min .

For this reason a 60 min preincubation was used in all the following experiments, in which atria rather than whole heart were studied . The PG contents in atrial tissue (ng/g tissue) were 78 .7 ± 17 .1, 85 .8 ± 12 .6 and 18 .7 ± 3 .7 for 6k PGF la , PGF 2a and PGE 2 , respectively . They resulted not significantly different from those measured in ventricles . However, in the ventricles significant amounts of PGE 1 and PGD2 were also detected . Finally, while the release of these PGs from atrial preparation into the medium was directly proportional to the incubation time, no time-related changes of PG levels in atrial tissue occurred when the incubation period was increased from 15 to 30 min . Thus rat heart utilizes endogenous arachidonic acid for the synthesis of PGs, mainly PGI 2 and PGF 2a that are continuously released into the extracellular space durinig incubation, while their levels remain constant .

REFERENCES 1) PACE-ASCIAK C .R . and RANGARAJ G . Distribution of prostaglandin biosynthetic pathways in several rat tissues . Formation of 6-ketoprostaglandin F la . Biochim . Biophys . Acta . 1977 ; 486 579-582 . 2) GRION A .M . and GALON R .M . Use of-HPLC for the study of prostaglandin release from rat tissues . Pharmacol . Res . 1990 ; 22 (3) : 113-114 .

Prostaglandins in rat heart.

Pharmacological Research, Vol. 25, Supplement 1, 1992 69 PROSTAGLANDINS IN RAT HEART P .BELLUCO, A .M .GAION, M .G .RICATTI, P .DORIGO and R .M .GAI...
97KB Sizes 0 Downloads 0 Views