THE EFFECT OF PROSTAGLANDIN E₁ ON RESPONSES OF SMOOTH MUSCLE TO CATECHOL AMINES, ANGIOTENSIN AND VASOPRESSIN

Abstract

Reduction of the pressor responses to adrenaline in the rabbit following administration of prostaglandin E1 has been confirmed. The effect is, however, nonspecific since noradrenaline, angiotensin and vasopressin are also antagonized. Analogous responses were observed in blood flow experiments on the cat hind limb but not on the rabbit isolated auricles or the rabbit isolated duodenum. Contractions of the cat nictitating membrane produced by sympathetic preganglionic stimulation or by adrenaline were not decreased following injection of prostaglandin E1 but the relaxation period was shorter. Contractions of the rabbit vas deferens induced in vivo by adrenaline were smaller after prostaglandin E1 and this effect tended to be longlasting.In 1938, Euler observed that pressor responses to adrenaline in the rabbit were reduced following an intravenous injection of prostaglandin. Steinberg, Vaughan, Nestel & Bergstr6m (1963) have recently made a similar observation using pure prostaglandin E1. These authors have also shown that the break-down of triglyceride in adipose tissue induced by catechol amines is antagonized. In this investigation we have confirmed the action of prostaglandin E1 on pressor responses to catechol amines and have shown that this effect is nonspecific since responses to angiotensin and vasopressin are also reduced. METHODSBlood pressure experiments. Blood pressure was recorded from a carotid artery using either a mercury manometer or a Statham pressure transducer. Cats were anaesthetized with pentobarbitone sodium (40 mg/kg), rabbits and rats with urethane (1.75 g/kg) injected intraperitoneally. In some experiments rats were anaesthetized with ether and pithed using a strong wire introduced through an orbit and passed down the cerebrospinal axis.Cat hind-limb blood flow. Cats, weighing 2.5 to 4.5 kg, were anaesthetized with pentobarbitone sodium (40 mg/kg) injected intraperitoneally. The trachea, a carotid artery and both external jugular veins were cannulated. Blood pressure was recorded by a mercury manometer. Venous outflow from a hind-limb was recorded by passing blood from the femoral vein through a Palmer drop-chamber connected to a Gaddum drop-recorder, the blood being returned into a jugular vein. The artery supplying the gracilis muscle was cannulated with fine polyethylene tubing connected to a three-way tap for retrograde intra-arterial injections. Heparin (1,000 U/kg) was injected intravenously and further doses of 500 U/kg were given every 2 hr. Contractions of the hind-limb muscles produced by stimulation of

Some effects of inhibiting endogenous prostaglandin formation on the responses of the cat spleen

“…Thus, the released prostaglandins act more by limiting the residual actions of the agonists (or the release of the transmitter) after the stimulus has been withdrawn. Holmes et al (1963) also found that prostaglandin E1 reduced the duration, but not the force of contraction of the cat nictitating membrane elicited by nerve stimulation. These results support the hypothesis that prostaglandin release attenuates the effects of nerve stimulation by a feed-back loop, but suggest that such a loop has a time constant measured in minutes rather than seconds.…”

ACTIONS OF PROSTAGLANDINS E1, E2 AND E3 ON THE CENTRAL NERVOUS SYSTEM

“…Such a dose injected intravenously into anaesthetized cats would cause a substantial fall in blood pressure (Holmes, Horton & Main, 1963), and therefore the possibility cannot be excluded that part of the short-lived sedative effect seen on intravenous injection is secondary to this fall of blood pressure. The effects following intraventricular injection, however, cannot be explained in this way, since by the intraventricular route much smaller doses were effective than on intravenous injection, and the effects were not only sedation but also stupor and catatonia.…”

The Effects of Deprivation of Prostaglandin Precursors on Vascular Sensitivity to Angiotensin Ii and on the Kidney in the Pregnant Rabbit

“…The mechanisms are incompletely understood, though they appear to act through several systems. The natriuretic and vasodilator actions on the kidneys (McGiff, Crowshaw & Ifskovitz, 1974) and peripheral vasculature (Holmes, Horton & Main, 1963) are probably of greatest importance. In addition to these, there are also relevant actions at adrenal (Dazord, Morera, Bertrand & Saez, 1974) and uteroplacental sites (Speroff, 1975).…”