Actions of lipoxidase on arterial pressure. III. Hypotensive action and anti-hypertensin activity

Abstract

The pharmacologic study of the fractions obtained by a chromatographic procedure from the lipoxidase proteins ob­ tained from the soybean, has yielded interesting results.

The outstanding one is that their hypotensive action is independent from the lipoxidase action proper.

Although fraction 2a shows a slight hypotensive action on test animáis without any sensible influence on the reflex hypertensive response to carotideal occlusion, it is fraction 4 which on the one hand is devoid of any lipoxidase power while on the other shows to possess the greatest hypotensive action both on the dog and the cat.

Hypotension induced in test animáis by the action of frac­ tion 4 shows peculiar features. In the first place, in none of the animáis treated (f. 3 B) is there any alteration whatsoever detectable during the first 30 minutes after the injection ; then, and only then. there appears a slow and progressive lowering of the animal blood pressure which reaches its máxi­ mum between one hour and two hours after the injection thus reaching a 50 % decrease as compared with the initial valúes.After that, hypotension begins to decrease also slowly and steadily until it fades away. On the other hand, parallel with the appearance of hypotension, the hypertensive reflex respon­ se to carotideal occlusion is progressively weakened, reaching in some cases an inverse response. to recover slowly and pro­ gressively its original intensity of normal response. It is to be remarked that not in all cases the acmé of the hypotension coincides with the greatest inhibition of the carotideal reflex.

The fact that hypotensive action and enzyme lipoxidasic activity appear independently from each other seems to implythat the hypotensive effect is not the result of -a peroxidative process. This is corroborated by the fact that the hypoten­ sive action is in no way modified by hepato-catalase, an enzyme capable of causing the transport of peroxidasic oxygen (per- oxidic action), and the decomposition of peroxides into oxygen plus water (catalase action) depending on the identity of the substrata and media upon which it acts. Thus, hepato-catalase may cliange in one or another sense the processes influenced by lipoxidase. This we were able to demónstrate.

That the hypotensive action is not the result of peroxidase processes could have been inferred a priori from the fact thathepato-catalase has no effect on it.

Now, it is quite difficult to explain the biochemical mecha- nism by which fraction 4 induces hypotension. However theresults of experimental reseárch in vitro, incubating the frac- tions together with hypertensine and with epineohrine throw some light into some of the organic processes involved. As we have seen, its inhibited effect on epinephrine is evidently linked with the lipoxidase action ; in the first place, because

it requires the presence of linoleic acid to take place ; secondly, because this inhibitive cffect is mainly manifest in the action of fraction 2a. But, in view of our results, the anti-hyperten- sine action is more interesting. In spite of the fact the inter- vention of hypertensine in the hipertensive processes is still a matter of discussion, our experimental researches point out that in the substances employed and fractions obtained by us there is a marked correlation between their hypotensive activity in the animal and their hipertensine-inhibiting activity in vitro.

We are at present engaged in the investigation of tlíe bio- chemical and pharmacological characteristics and properties of fraction 4. Since this substance is of a very low toxicity (DIv50 in the mouse is more than 1000 mg/kg) we are begin- ning to test it in sóme human patients suffering from blood hypertension.