The Effect of Posterior Lobe Pituitary Extracts on Blood Pressure in Several Vertebrate Classes

In 1895 Oliver & Schaefer showed that pithed cats responded to injections of pituitary extracts with a rise of blood pressure. It was later shown (Howell, 1898) that the active substance was contained in the posterior lobe. Paton & Watson (1912) described a fall in blood pressure in decapitated ducks following injection of posterior lobe extracts. Hogben & Schlapp (1924) confirmed these results and recorded the effect of injections of whole posterior lobe extract in amphibians and reptiles.

When the posterior lobe fractions, pitocin and pitressin, became available it was shown that the mammalian pressor response was evoked by pitressin (Kamm, Aldrich, Grote, Rowe & Bugbee, 1928), pitocin having no significant effect, whereas both pitressin and pitocin evoked a fall in the fowl, pitocin being more potent (Gaddum, 1928).

Since Hogben & Schlapp had shown that the predominant effect of whole posterior lobe extract was pressor in amphibians and placental mammals, while in reptiles and birds it was depressor, the observations of Kamm and Gaddum invited investigations of the responses to pitocin and pitressin in different vertebrate classes with the object of deciding whether the results had phylogenetic significance.

Sawyer & Sawyer (1952) found that the amphibians Bufo marinus and Rana catesbiana exhibited a depressor response to pitocin, while pitressin had no effect in Bufo and evoked a rise, fall or diphasic response in Rana. Of reptiles, the alligator (Sawyer & Sawyer, 1952) behaved similarly to Rana and the turtle (Woodbury & Abreu, 1944) exhibited a depression to pitocin. Only two birds appear to have been investigated. The fowl (Coon, 1939; Strahan & Waring, 1954) always depresses to pitocin and, except in certain cases of low basal blood pressure and when the preparation is tolerant to pitocin, depresses to pitressin also. The pigeon (Waring, Morris & Stephens, 1956) depresses to pitocin and always shows a rise to pitressin. Feakes, Hodgkin, Strahan & Waring (1950) found that in a mono-treme (Ornithorhyncus) pitocin evoked a fall and pitressin a rise in pressure. The foregoing information permits the generalization that all land vertebrates below the placental mammals depress to pitocin and different ones, even in the same class, show a variety of response to pitressin. On the other hand, placentals uniformly show a rise to pitressin and no response to pitocin. Feakes et al. were so impressed by the pitocin-depressor response of the platypus that they emphasized this mono-treme mammal’s affinity to reptiles.

The present paper records observations on a variety of species; the aim being to see whether any phylogenetic significance could be attributed to the responses recorded.

Observations on the vascular responses to mammalian posterior lobe pituitary fractions (pitocin and pitressin) were made on the following species:

Amphibia—toad (Bufo marinus), 4 specimens.

Reptilia—tortoise (Chelodina oblonga), 5 specimens; lizard (Trachysaurus rugosus), 3 specimens.

Aves—penguin (Eudyptula minor), 5 specimens ; emu (Dromaius novae-hollandiae), 2 specimens; cormorant (Phalocrocorox varius), 3 specimens.

Mammalia—possum (Trichosurus vulpécula), 4 specimens; wallaby (Setonix brachyurus), 5 specimens.

• Anaesthesia. Toads were anaesthetized with intraperitoneal injections of Dial Ciba or they were pithed. The most satisfactory anaesthetic for tortoises was a 10% solution of sodium phenobarbitone administered intramuscularly and then intravenously. The lizards were anaesthetized either with ether or with Nembutal injected intraperitoneally. All the birds were anaesthetized with an aqueous solution of sodium phenobarbitone. For the emus a 25% solution was injected intramuscularly, while the penguins and cormorants were injected initially with a 10% solution intramuscularly and, when sufficiently quiet, anaesthetization was completed with intravenous injections. Possums were anaesthetized with intraperitoneal injections of Dial Ciba (120 mg./kg.) and wallabies with either intraperitoneal injections of Dial Ciba (200 mg./kg.) or intramuscular injections of paraldehyde (2 ml./kg.).

• Blood pressure recordings were made from a cannulated artery connected to a mercury manometer. Before inserting the arterial cannula heparin (1000 i.u./kg.) was injected into the circulation to prevent coagulation. Injections of pitocin and pitressin (Parke Davis) were made via a cannula inserted in a vein. Dilutions of pituitary extracts were made with frog Ringer for experiments on toads, 0-7 % NaCl solution for experiments on reptiles and 0·9% NaCl solution for experiments on birds and mammals. Control injections of saline were made in all animals. Owing to the small size of the toads the largest blood vessels had to be cannulated; without totally excluding large areas of the body from circulation satisfactory preparations were obtained using one of the systemic arteries and the femoral vein immediately before its junction with the anterior abdominal vein. The carotid artery and jugular vein were found to be the most suitable for cannulation in the tortoise and lizard. In the birds blood pressure was recorded from the sciatic artery and injections were made into either the brachial vein (cormorant) or the femoral vein (penguin and emu). The carotid artery and jugular vein were cannulated in possums and wallabies.

Toad. Feakes’s (unpublished) investigation of the responses of the toad to posterior lobe pituitary extracts showed a pressor response to both pitocin (5–30 i.u./kg.) and pitressin (10-100 i.u./kg.); her toads were pithed, or anaesthetized with Dial. Further experiments confirm these results. Pithed and anaesthetized animals respond with a prolonged rise to both pitocin and pitressin (Pl. 5, A) and after a series of injections of equal doses of either pitocin or pitressin the preparation becomes less sensitive [i.e. tolerance develops (Pl. 6, A, B)]. Using similar doses, Sawyer & Sawyer (1952) observed depressor responses to both pitocin and pitressin.

Tortoise. Anaesthetized tortoises respond to injections of both pitocin and pitressin with a slow rise in blood pressure (Pl. 5, B). Tolerance develops with serial injections (Pl. 6, C, D). Pressor responses to pitocin and pitressin were obtained by Feakes (unpublished) in one experiment on a tortoise which had been pithed.

Lizard. Feakes et al. (1950), using Trachysaurus rugosus, anaesthetized with ether, described a depressor response to pitocin and a pressor response to pitressin. I have been unable to confirm this. In my experiments, with animals anaesthetized with ether or Nembutal, both pitocin and pitressin evoked depressor responses (Pl. 5, C). Tolerance develops with serial injections (Pl. 6, E, F).

Penguin. Pitocin evokes a fall in blood pressure and tolerance develops with serial injections. The response to pitressin was predominantly a fall in blood pressure which was sometimes preceded by a small rise. The depressor response to pitressin was obtained at all basal blood pressures between 2 and 12 cm. Hg and serial injections led to a tolerant state. The qualitative responses to pitocin and pitressin are illustrated in Pl. 5, D, and the tolerance which develops to serial injections in Pl. 7, G, H.

Emu. Two anaesthetized emus exhibited depressions to both pitocin and pitressin (Pl. 5, E). The depressor response to pitressin was obtained at base pressures between 3·4 and 10·4 cm. Hg. No information on the development of tolerance with serial injections was obtained in these experiments.

Cormorant. Small doses of both pitocin and pitressin evoke large blood pressure responses in this species. Injection of pitocin produced an initial sharp depression which was sometimes followed by one or two further falls before the base pressure returned to the pre-injection level (Pl. 5, F). The response to pitressin was a depression, which was sometimes followed by a further fall and/or a rise (Pl. 5, F). Partial tolerance developed with serial injections of pitressin (Pl. 7, I). No tolerance to serial injections of pitocin could be demonstrated.

Possum. Preliminary experiments by Feakes were made on animals anaesthetized with Dial and urethane: a pressor response to pitressin was obtained. Further experiments confirmed this response (Pl. 5, G). It was also found that partial tolerance could be induced with serial injections of pitressin (Pl. 7, J). Injections of small doses of pitocin had no effect on blood pressure; with large doses a rise occurred which could be accounted for on the basis of the 4% pitressin contamination of pitocin.

Wallaby. Pitressin evokes a pressor response and partial tolerance is developed with serial injections. The responses to small and large doses of pitocin were the same as those obtained in the possum.

Placentals and marsupials are insensitive to pitocin; all other forms investigated, except Bufo and Chelodina, depress to pitocin. Chelodina exhibits a rise to pitocin; the results reported here on Bufo (a rise) are opposite to those reported by Sawyer & Sawyer (1952).

The response to pitressin is much more variable. Amphibia exhibit a fall, rise or diphasic response, reptiles a rise or diphasic response, birds a fall except for the pigeon, and all three subclasses of mammals, a rise. When we had results from onl two birds, pigeon and fowl, we were encouraged to examine others to see whether flying and terrestrial species differed consistently; this is not sustained by results from a cormorant, a flying bird.

The observation by Feakes et al. (1950) that, like all reptiles investigated up to that time, a monotreme exhibited a depressor response to pitocin encouraged the earlier suggestion that there might be correspondence between the vascular responses to posterior lobe pituitary extracts and phyletic position. Table 1 shows that this proposition can no longer be entertained. Thus within Reptilia different species of Chelonia exhibit opposite responses to pitocin, and within both Reptilia and Aves different species exhibit opposite responses to pitressin.

Whether the responses under consideration are pharmacological artifacts or have physiological significance is not strictly germane to our object Nevertheless, when doses are converted to dose level/kg. as in Table 1 it is clear that for mammals and birds the excitant dose is such that it could be supplied by endogenous secretion, that in reptiles it probably could not, and for amphibians almost certainly not. So, sensitivity of peripheral vessels to mammalian posterior lobe excitants has increased with the evolution of higher forms.

I am indebted to M. Feakes for permission to mention unpublished results. Salary and some expenses were met by an N.H.M.R.C. grant to Prof. Waring; some expenses were met from a Western Australian University research grant.