Effect of serotonin on the blood pressure in cats

Abstract

Serotonin was intravenously administered in variable doses, between 0,65 and 2,7 mg/kg to : normal cats, cats suffering from bilateral vagotomy, cats with denervated carotid sinuses, normal cats or those suffering from bilateral vagotomy under contiuued injection of histamine (1-3 /xg/kg. min.) or adrenali- nc (3,5-4,5 /¿g/kg. min.).

In normal cats serotonin produces a strong and abrupt de­ crease of arterial pressure, acompanied by bradicardia and apnea (Bezold-Jarisch effect), followed by a slow rise of pres­ sure, but without reaching valúes above the initial one (graphs

1, a, b). The magnitude of the dose injected affects only the valué of the initial hypotension. Thus, the greater the dose, the greater the decrease in pressure.

In cats suffering from bilateral vagotomy and with dener­ vated carotid sinuses the initial hypotension phase does not appear, being observed in its place a brief but marked pressure

wave, followed sometimes by a depressing w(ave which reesta- blishes the initial pressure (graph 2, a) and other times by an abrupt depression Which makes is fall below the initial valué (graph 2, b) or just as well by a gradually progresive hypo­ tension.

In cats with intact vagi nerves and denervated carotid sinu­ ses, serotonin produces analogous effects to those obtained with normal cats (graph 3, a y b).

In cats suffering from bilateral vagojomy but with intact carotid sinuses the initial abrupt hypotension appears but it is very brief and not so intense as in normal cats . It is followed by a rapid increase in pressure until the initial valué is reached or surpassed (graph 4).

In normal cats under continuous injection of histamine, se­ rotonin produces : abrupt and intense hypotension, rapid in­ crease of pressure until reaching valúes above the initial one and gradued descent of pressure which is stabilized at a level slightlj’- below the initial valué (graph 5). In some cases the hypertensive phase is lacking ; in these cases the hipotensive pase is followed by a slow¡ and gradual increase, pressure being stabilized at a level slightly below the initial valué.

In cats sttffering from bilateral vagot.omy and. contínuously injected with histamine serotonin produces the same effects as in those cats suffering from bilateral vagotomy and denervated carotid sinuses without injection of histamine : this is a bi- phasic response, hypertensión and hypotension (graph 6)

ln normal cats under continuous injeotion of adrenalina

an abrupt and intense hypotension is observed followed by a rise in waves until reaching valúes much higher than the initial oue (graph 7, a) afterw¿ards pressure falls being stabilized at a slightly lower level.

In cats suffering from bilateral vagotomy tender continuous injection of adrenaline, serotonin produces a low intensity ini­ tial hypotension (graph 8, a), slightly marked or it does not appear at all (graph 8, b). In the first two cases the hypotension is followed by a hypertensive phase. In the third case the hy- pertensive phase appears instead of the lacking initial hypo- tensive phase. Afterwards, in all cases pressure falls gradually until reaching valúes equal to the initial one.

It is atributed the first hypotension which appears in nor­ mal cats to a reflex action (Bezold reflex and depressing reflex) since in cats suffering from bilateral vagotomj'- and denerva- ted carotid sinuses hypertension appears instead of the initial hypotension. When carotid sinuses are denervated but vagal innervation is conserved the initial hypotensive phase persists althoug it is very brief in some cases. Whenever vagal innerva­ tion is supressed but innervation of carotid sinuses remains in­ tact, abrupt hypotension is also produced but it is much briefer and does not reach valúes as low as in normal cats.

The action of the vagi nerves or the carotid sinuses is suffl- cient to produce the initial hjpotensive phase but it is only when both are intact that hypotension is intense in all cases.

In cats under continuous injection of histamine, a bilateral vagotomy is enough to prevent the initial hypotension produced otherwise by the serotonin. It seems as if the histamine acted preventiug the depressive action of the serotonin on the sinuses.

Bilateral vagotomy in cats injected continuosly with adre- naline reduces or prevenís the initial hypotensive responso. Thus it seems that the adrenaline would act also exerting a bracking action on the depresing reaction but this bracking action would be less intense tahn that of the histamine.

In normal cats serotonin, even in large doses, never produces a hypertensive phase. Nevertheless this phase appears in our experiment in the following circumstances : l.° always, in cats suffering from bilateral vagotomy and denervated carotid si­ nuses. 2o in some cats whose vagal innervation has beeu cut even thoug they conserve their carotid sinuses intact. 3° in all of our cats under continuous injection of histamine or adrenaline, ei- ther normal or suffering from bilateral vagotomy. This hyper­ tension inay be explained by admitting that serotonin exerts a double action on the arterial pressure : a vasodilator action by provoking the Bezold and the carotid and aortic depresor

reflexes, by acting directly on the respective receptors ; a vaso­ constrictor action which may be due to múltiple factors, o£ which the most important one seems to be peripheric vasoconstriction.

On suppresing the vasodilator action reflex by cutting the vagi and denervating the sinuses or on diminishing it by cutting the vagi or denervating the sinuses, the vasoconstrictor action would predomínate and hypertension would appear.

Histamine or adrenaliue apparently act by reenforcing the pressure action of the serotonin, but as yet \ve cannot explain by which mechanism.

We do not think that prolonged hypotension could be atri- buted to a liberation of histamine ; since whenever our cats trea- ted x^ith histamine were deprived of their vagal innervation this hypotension would be very intense and would not be so intense if vagal innervation remained intact. In our opinión this varia- tion should not appear if serotonin acted liberating histamine.

We think also that the cause of prolonged hypotension is not to be found on the influence exected by depressing reflexes ;since in our cats w.ithout carotid sinuses níƒor vagal innervation, a marked and prolonged hypotension is observed. In cats suffe- ring from bilateral vagotomy, hypotension is less marked and it is variable normal cats and in those with denervated sinuses.