T.J. Malkinson

The action of centrally administered arginine vasopressin on blood pressure in the conscious rabbit

In addition to its peripheral endocrine actions, arginine vasopressin (AVP) has been implicated in the central control of blood pressure. Intracerebroventricular (i.c.v.) injections (0.01-1.0 nmol) of AVP or arginine vasotocin (AVT), but not oxytocin (OXY), into unanesthetized rabbits caused a rapid, dose related rise in blood pressure as well as increases in heart rate. The lowest centrally administered dose of AVP and AVT (0.01 nmol) had no effect on blood pressure when given intravenously. In search of tissue locus for the pressor effect of AVP microinjection of AVP and OXY into the posterior hypothalamus and septum of conscious rabbits was without effect. However, microinjection (0.01-0.04 nmol) of AVP into the nucleus tractus solitarius of anesthetized rabbits caused a rise in blood pressure similar to the response seen after i.c.v. injection. Comparable volumes of the vehicle into the ventricle or the tissue sites had no effect on resting blood pressure. The pressor response after AVP given i.c.v. was significantly reduced up to 3 h after administration of the ganglionic blocker, chlorisondamine HCl. The central antagonist, d(CH2)5Tyr (Me) vasopressin, eliminated the usual increase in blood pressure after administration of AVP in half the animals tested. The results indicate that AVP acts centrally to mediate cardiovascular responses in unanesthetized as well as anesthetized rabbits.

The role of vasopressin as an antipyretic in the ventral septal area and its possible involvement in convulsive disorders

Perfusion of the peptide, arginine vasopressin (AVP), within the ventral septal area (VSA) of the brain of a number of species reduces fever but not normal body temperature. This antipyretic response appears to be mediated by AVP receptors of the V1 subtype. Lesions of the VSA with kainic acid are associated with prolonged and enhanced fevers in rats. A role for endogenous AVP in fever suppression within the VSA comes from several types of experiments: (1) AVP release within the VSA is inversely correlated to fever height; (2) AVP antagonists or antiserum injected into the VSA prolong fever; (3) animals lacking endogenous AVP in the VSA (Brattleboro rat, long-term castrated rat) develop enhanced fevers. Electrical stimulation of the AVP-containing cell bodies of the bed nucleus of the stria terminalis (BST) orthodromically inhibits VSA neurons and also suppresses fever; the latter effect can be abolished with application of a V1 antagonist to the VSA. Iontophoretic studies indicate that AVP inhibits glutamate-stimulated activity of thermoresponsive and other VSA neurons. AVP can also act in the VSA to cause severe motor disturbances; this action is receptor mediated and increases in severity upon sequential exposure to AVP. Because sites of action of the antipyretic and convulsive action of AVP are similar, and because animals lacking brain AVP display reduced convulsive activity, it is possible that AVP, released during fever, could be involved in the genesis of convulsive activity.

Prostaglandin Fever in Rats Throughout the Estrous Cycle Late Pregnancy and Post Parturition

We have examined the influence of natural variations in endocrine status on the ability to generate a prostaglandin‐induced fever in virgin female, pregnant and lactating rats and compared responses to those in male rats. Endocrine status of virgin female rats was assessed from examination of vaginal smears and time of parturition noted to enable accurate dating of pre‐ and postparturient fevers. Unanesthetized rats, previously prepared with intraventricular guide cannulas and intraperitoneal telemetry thermistors, were given intraventricular injections of prostaglandin E, (2–100 ng/5 μl) and temperatures monitored for 3 h after injection. Virgin females developed significantly larger fevers than did males at higher doses. There were no significant alterations in either fever height or duration as a function of the phase of the reproductive cycle in the females. Both pregnant and postparturient rats within the several days around birth displayed significantly lower fevers than did virgin females, but there was no further reduction in the immediate periparturient period. These data indicate that there are sex‐, and possibly hormone‐dependent differences in the central mechanisms involved in fever generation and antipyresis.

Depletion of brain α-MSH alters prostaglandin and interleukin fever in rats

Abstract Alpha-melanocyte stimulating hormone (α-MSH), a putative endogenous antipyretic agent, is synthesized largely within neurons in the arcuate nucleus. To test the hypothesis that destruction of this area would increase the febrile response, male Wistar rats, treated as neonates with intraperitoneal injections of monosodium glutamate (MSG) or saline, were given intracerebroventricular (i.c.v.) injections of prostaglandin E1 (20 ng; 200 ng) or purified interleukin-1 (20 U) and body temperature was monitored. The fevers displayed by the MSG-treated animals were significantly greater (P

Induced changes in intracranial pressure in the anesthetized rat and rabbit

Intracranial pressure (ICP) was measured continuously in anesthetized, free-breathing, adult, male Sprague-Dawley rats and New Zealand White rabbits by means of a subarachnoid screw technique. The effect upon ICP of changing the volumes within the cranium by infusion of artificial cerebrospinal fluid into the lateral cerebral ventricle at various rates was examined. Results obtained demonstrated some of the elastic and compensatory aspects of cerebrospinal fluid dynamics. The effects upon ICP of the intravenous administration of urea, mannitol, acetazolamide, dimethyl sulfoxide, norepinephrine, epinephrine, isoproterenol, nitroglycerin, papaverine, histamine, angiotension II, pitressin, sodium nitroprusside, diazoxide, lidocaine, sodium pentobarbitone, as well as inhalation of amyl nitrate and carbon dioxide were examined in anesthetized rats. The effect upon ICP of the intravenous infusion of urea, as well as the bolus intravenous administration of epinephrine and pitressin was examined in the anesthetized rabbit. Results obtained from these animals demonstrate the action of these experimental interventions upon ICP as measured by means of the subarachnoid screw technique.

A simple multi-purpose cannula system for access to the brain and/or systemic vascular system of unanesthetized animals

By utilizing a pedestal system mounted on the skull containing a cerebral guide cannula with hub, and a vascular catheter which is exteriorized within the pedestal, an easily made, multi-purpose system has been developed using materials which are available from any scientific or medical supplier. This technique is adaptable for use in a wide variety of animal species and can be used in unanesthetized or anesthetized preparations.

Prostaglandin fever in rats is altered by kainic acid lesions of the ventral septal area

The ventral septal area (VSA) has been shown to be a region within the rat brain where arginine vasopressin (AVP) acts to reduce fever. To test the hypothesis that destruction of this area would affect the magnitude of the febrile response, body temperature was monitored in male, Wistar rats given intracerebroventricular injections of prostaglandin E1 (200 ng) and saline (10 microliter) before and after bilateral injections of kainic acid (KA) or of saline vehicle into the VSA. While fever heights were unaffected by the lesion, fever in the KA-lesioned animals remained significantly elevated (P less than 0.05) for 1 h after the peak response. There was no significant difference in the fever responses displayed by sham-lesioned animals. The body temperature response of non-febrile animals to high or low ambient temperature was unaffected by the lesions. The enhanced fever following the KA lesion, but not sham lesions of the VSA would support the hypothesis that this region is involved in endogenous suppression of fever.

Vasopressin perfusion within the medial amygdaloid nucleus attenuates prostaglandin fever in the urethane-anaesthetized rat

The antipyretic effect of arginine vasopressin (AVP) introduced into the ventral septal area (VSA) by push-pull perfusion was investigated in the urethane-anaesthetized rat. In addition, experiments were carried out to determine whether AVP could suppress fever when similarly perfused within the medial amygdaloid nucleus (meA). During push-pull perfusion of artificial cerebrospinal fluid within the VSA or meA, PGE1 injected intracerebroventricularly evoked fevers with respective magnitudes of 1.3 +/- 0.2 degrees C and 1.4 +/- 0.3 degrees C above baseline. Perfusion of AVP (6.5 micrograms/ml) within the VSA had significantly reduced the magnitude of PGE1 fever to 0.3 +/- 0.3 degrees C above baseline, while having no significant effect on afebrile colonic temperature. Perfusion of AVP (6.5 micrograms/ml) within the meA had significantly attenuated the magnitude of PGE1 fever to 0.7 +/- 0.2 degrees C above baseline, while having no significant effect on afebrile colonic temperature. These results support further the utility of the urethane-anaesthetized rat model for future investigations of the central control of fever and antipyresis. In addition, these data are consistent with the hypothesis that AVP may act within the meA as an endogenous antipyretic.

Measurement of intracranial pressure in the unanesthetized rabbit

A method is described for the measurement of intracranial pressure in the unanesthetized, minimally restrained rabbit utilizing a modified subarachnoid screw system. The pressures are transmitted from within the cranium via a flexible saline filled catheter to a fixed external pressure transducer. An index of the relative vertical position of the animals skull as compared to the fixed transducer is given by means of a second open-ended pressure measuring catheter, the open end of which is fixed to the subarachnoid screw assembly on the animals skull. The system was found to be a reliable method of measurement of intracranial pressures in the minimally restrained rabbit, and could easily be adapted to other animal species. The method is currently being used to assess the effects of fever on intracranial pressures.

Brain calcium in the rabbit: Site of action for the alteration of body temperature

Body temperature was recorded in the unanesthetized rabbit during push-pull perfusion of regions of the hypothalamus. Both the anterior and posterior hypothalamus were perfused with physiological solutions containing Ca++ in a concentration 2.0 or 5.0 times that of extracellular fluid. The animals were placed in an ambient temperature of 4.0 +/- 2.0degrees C for at least 1 hr before the perfusion and all experiments were carried out at this temperature. In the posterior hypothalamic area Ca++ produced a sharp fall in body temperature but did not cause body temperature to alter when it was perfused through the anterior hypothalamic area. These results indicate that the rabbit is similar to the cat and monkey since the effect of Ca++ on body temperature is localized to the posterior hypothalamic region.