Prostaglandins and medicine最新文献

Effects of aldosterone and spironolactone on the vascular responses to noradrenaline and potassium were studied in the perfused rat mesenteric vascular bed. Aldosterone did not modify the response to either vascular agent. Spironolactone inhibited the vascular response to both pressor agents in a dose-dependent manner. The inhibitory effect of spironolactone was not altered by various concentrations of aldosterone and ouabain. However it was not apparent in preparations in which endogenous prostaglandin synthesis had been abolished by indomethacin. The observations suggest that spironolactone has actions on vascular reactivity which are not related to aldosterone or to sodium/potassium pumping. They may depend on modification of prostaglandin biosynthesis.

Urinary prostaglandin (PGE₂) and plasma renin activity (PRA) were determined in 3 groups of hypertensive patients before and following 5 days of treatment withdifferent antihypertensive drugs. In all 3 groups studied a substantial decrease of blood pressure was noted following treatment. However, whereas administration of chlorthalidone and hydralazine initiated a significant rise of PGE₂ and PRA excretion, treatment with propranolol was associated with a decrease of these two parameters.

In view of these findings it seems therefore as if renal production of PGE₂ (at least with regard to propranolol, a β-blocking agent), is not related to the hypotensive effect of the drug.

Interactions between dopamine and responses to noradrenaline as modulated by prostaglandins (PGs) were studied in the perfused rat mesenteric vascular bed. When perfused alone dopamine up to a concentration of 10⁻⁷M neither changed baseline pressure nor modified the pressor response to noradrenaline. Dopamine at 10⁻⁹ to 10⁻⁷M significantly inhibited responses to noradrenaline which had been enhanced by the presence of 10⁻¹⁰ to 10⁻⁸ M PGEI. In preparations in which vascular responses to noradrenaline had been abolised by indomethacin and restored by adding PGEI, 10⁻⁹ to 1⁻⁷M dopamine significantly inhibited the restored responses. Dopamine also attenuated the inhibitory effects of prostacyclin on pressor responses to noradrenaline but it did not change the actions of either PGE2 or PGF2 alpha. Pimozide, a mainly centrally acting dopamine antagonist, did not interfere with these peripheral actions of dopamine. The dopamine effects were blocked by another dopamine antagonist, metoclopramide. Dopamine can inhibit the effects of PGEI and prostacyclin in the rat mesenteric vascular bed, possibly by interacting with specific dopamine receptors.

We studied the effects of prostacyclin on pattern of breathing in six anaesthetized pigs with aortic obstruction. PGI₂ causes a rightward displacement of VT/T relationship (Hering-Breuer threshold curve) without a corresponding change I respiratory flow. With airways occluded at the end expiratory level, we analyzed how PGI affects the central respiratory rhythm in the absence of the phasic lung volumi-related vagal loop. Infusion of prostacyclin causes leftward displacement of the T /T relationship and an increase in T o correlated with the hypotensive action The change in the bulbo-pontine pacemaker is caused by a marked increase in T , and this suggests that PGI can modulate the central respiratory rhythm, inde$endently of the blood pressure level.

Inhibition of collagen-induced platelet aggregation by either endothelial extracts, prostacyclin, prostaglandin E₁ or prostaglandin D2 was investigated. The inhibition was less efficient with diabetic platelets than with platelets from normal donors. The refractoriness of diabetic platelets to inhibitory prostaglandins was observed both with platelet-rich plasma and platelets isolated from their plasma. Moreover, levels of cyclic AMP in resting platelets and after stimulation by either PGE₁ or PGD₂ were lower in diabetic platelets than in normal platelets. It is concluded that the weaker response of diabetic platelets to inhibitory prostaglandins could be related to their content in cyclic AMP.

Age and sex related platelet biosynthesis of prostaglandins, thromboxane B₂, prostaglandin endoperoxides, HHT and HETE was studied in normal human subjects and in acute myocardial infarction (AMI) patients (all males over 50 yr). The following results were obtained. 1. No significant difference was observed in the platelet biosynthesis of prostaglandins (F_2α, E₂, D₂ ), TxB₂ and HHT in normal subjects when values of these arachidonic acid metabolites were compared for different age groups and sex. 2. HETE formation in females was significantly more (p < 0.001) than that in males. 3. No significant difference was observed in the prostaglandin endoperoxide level (PGG₂, PGH₂ + PGF_2α) amongst different age groups and sex in the normal subjects and this was so when compared with AMI patients. 4. Significantly less TxB₂ was produced by platelets from the AMI patients compared to normal males over 50 years. 5. In AMI patients, platelets produced significantly more HHT (p < 0.005) and PGF_2α (p < 0.02) compared to normal males over 50 years. 6. A significantly reduced (p < 0.005) formation of HETE in the AMI patients compared to normal males (over 50 yr) was observed. A comparison of ratios between HHT, HETE and TxB₂ for normal males (over 50 yr) and AMI patients was made for their possible use in diagnostic purposes.

These results have been discussed in the light of the existing knowledge about the aggregation and antiaggregation properties of various AA metabolites.

The peripheral venous plasma levels of thromboxane B₂ (TxB₂) were determined by radioimmunoassay in 22 control subjects, 12 patients with essential hypertension, 15 patients with cerebrovascular disease (CVD) not taking aspirin and 14 patients with CVD taking aspirin. There was no significant difference in TxB₂ levels among the control subjects, hypertensive patients and CVD patients not taking aspirin. In CVD patients taking aspirin, the plasma TxB₂ levels were significantly lower than those in the other groups. The internal jugular venous concentrations of TxB₂ were measured in 10 CVD patients not taking aspirin. Four of 10 studied patients exhibited significant increases only in the internal jugular venous TxB₂ levels, while peripheral venous and/or femoral arterial TxB₂ levels were not significantly different from peripheral venous TxB₂ levels of control subjects.

The prelabelling technique (incorporation of (1-¹⁴C)-arachidonic acid was used to investigate the influence of ricinoleic acid on prostaglandin biosynthesis in peripheral vessels. Infusion of ricinoleic acid (0.2 mM) intra-arterially into the isolated perfused ear stimulated the release of labelled arachidonic acid and metabolites. The major metabolite released was PGE₂ followed by PGI₂ (measured as 6-keto-PGF_1α ) and PGD₂ Prostaglandin release was abolished by indometacin (3 μg/ml) and strongly reduced by perfusion with calcium-free, 1 mM EGTA containing solution. In the presence of bovine serum albumin there was a basal release of high amounts of arachidonic acid. Ricinoleic acid tended to increase the released amount of labelled arachidonic acid. In contrast to indometacin, perfusion with calcium-free, 1 mM EGTA containing solution tended to reduce the release of arachidonic acid. The results show that in the peripheral vascular bed ricinoleic acid stimulates the release of arachidonic acid and metabolites probably by activating a calcium-dependent phospholipase A₂. Since ricinoleic acid is well absorbed from the gut, such an effect may occur after ingestion of a highly laxative dose.