Differential effects on naloxone on the release of neurohypophysial hormones in normotensive and spontaneously hypertensive rats

The hypothalamo-neurohypophysial system is altered in the spontaneously hypertensive rat (SHR). We hypothesized that an aberrant regulation of vasopressin (VP) and oxytocin (OT) release by endogenous opiod peptides alters this neuroendocrine system in the SHR. Concentrations of the neurohypophysial hormones in plasma and the pituitary were measured in 17-week-old SHRs and two strains of normotensive controls, Wistar Kyoto (WKY) and Sprague-Dawley rats. Animals were decapitated 20 min after s.c. injection of saline (1 ml/kg) or naloxone hydrochloride (1 or 10 mg/kg). In addition, neurohypophysial hormones excreted during the day (08.00–17.30 h) and night (17.30–08.00 h) were determined in urine from 16-week-old animals kept in metabolic cages for 5 days. VP at extrahypothalamic sites was also measured as [VP] in acid extracts of the subfornical organ area, hippocampal commissure-fornix and choriod plexus. Hormones were quantified by radioimmunoassay. The pituitary content, plasma concentration, and urinary excretion of OT were reduced (P < 0.05) in SHRs, whereas VP content was increased (P < 0.05) in the pituitary and plasma, but unchanged in urine, of hypertensive animals. In extrahypothalamic tissues, [VP] in the hippocampal commissure-fornix was increased in the SHR. Naloxone elevated (P < 0.05) the plasma concentration of OT in WKY animals and VP in SHRs. Neither [VP] nor [OT] in plasma was changed by naloxone in Sprague-Dawley rats. Pituitary stores of the neurohypophysial hormones were not altered by naloxone in either hypertensive or normotensive rats. In conclusion, endogenous opioid peptides tonically inhibit OT release in WKY rats, whereas VP releas is decreased by opioid peptides in SHRs, 16–17 weeks of age. The neuromodulatory role of opioid peptides in the release of neurohypophysial hormones appears to be altered in the SHR such that VP release is suppressed and OT release is augmented.     

Cerebral vasomotor reactivity in normotensive and spontaneously hypertensive rats

Intravenously injected metaraminol induced a larger blood pressure increase in spontaneously hypertensive rats (SHR) than in normotensive controls (NR) when the pressure was raised from the same starting level. Cerebral blood flow (CBF) response in NR was either perfect autoregulation, partial autoregulation or "break-through." When present, the autoregulatory response was very rapid, i.e. the flow returned to the initial value within 10-15 sec. All SHR showed an initial prompt vasoconstrictor response which was followed after 30-40 sec by a gradual flow increase. The blood pressure elevation was highest in SHR when hypertension was induced by compression of the aorta, which supports the hypothesis that the enhanced response is, at least in part, a consequence of an increased vessel wall to lumen ratio. The characteristic CBF pattern observed in SHR after a metaraminol-induced rise in blood pressure was not seen when the blood pressure was increased by aortic compression, which suggests an effect of the drug separate from its pressor effect. During maximum vasodilatation the cerebrovascular resistance (CVR) was considerably higher in SHR than in NR. Assuming an equivalent vessel density in the 2 groups, our results suggest that structural changes in resistance vessels in SHR encroach on the lumen.     

Effects of acute hypertension on brain metabolism in normotensive, renovascular hypertensive and spontaneously hypertensive rats

Effects of angiotensin-induced acute hypertension on cerebral metabolism were studied in normotensive (NTR), spontaneously hypertensive (SHR) and experimental renovascular hypertensive rats (RHR). Lactate, pyruvate and adenosine triphosphate (ATP) concentrations in the brain frozen in situ at 18--20 min after angiotensin infusion, which raised mean arterial pressure (MAP) by 28--62% of control, were determined by enzymatic methods. Supratentorial lactate was significantly increased to 135% of control in RHR, its increase being correlated with the degree of hypertension, wherease it remained unchanged in NTR or SHR. Furthermore, RHR showed a tendency toward increase in lactate/pyruvate ratio with a decrease in ATP despite no change of arterial acid-base balance measured simultaneously before and after acute induced hypertension. From the present study, it is postulated that some renal factor seems to contribute ischemic metabolic changes in RHR following acute hypertension. The possible effect of renin on the vascular permeability is discussed as the pathogenesis of hypertensive encephalopathy.     

Carotid and aortic bodies in chronically anemic normotensive and spontaneously hypertensive rats

Overactivity of the carotid body chemoreceptors along with the enlargement of chemoreceptor tissue were found in spontaneously hypertensive rats of Okamoto-Aoki strain (SHR). The purpose of the present study was to answer the question whether the aortic bodies were also enlarged in SHR. However, because aortic bodies, unlike carotid ones, are sensitive to oxygen content another question arose: do aortic bodies undergo hypertrophy in chronic anemia? Twenty-three spontaneously hypertensive rats of Okamoto-Aoki strain (SHR) and 24 normotensive Wistar rats (NCR) were maintained on low-iron food from the age of 3 weeks. In seven 10-week-old anemic SHR regular diet was substituted (transiently anemic SHR). Blood pressure measurements and hemoglobin were measured every second week. The animals were killed at the age of 18 weeks. Light microscopic studies of the carotid and aortic bodies were performed and volumes of chemoreceptor tissues were determined from serial sections. The eight SHR on low-iron diet exhibited lower hemoglobin concentration than their normotensive counterparts. In the anemic SHR blood pressure was lower than in control SHR, whereas blood pressure did not differ between the anemic and control NCR. Restoration of normal values of hemoglobin in the anemic SHR was followed by only a slight increase in blood pressure. The carotid bodies volumes were 2.5-3 times larger in the SHR than in NCR. The volumes of carotid bodies both of the SHR and NCR were influenced neither by blood pressure nor by hemoglobin concentration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Locomotor activity and catecholamine receptor binding in adult normotensive and spontaneously hypertensive rats

Summary The binding of³H-WB 4101, an ₁-adrenoceptor antagonist, to membranes of the cerebral cortex, the hypothalamus, and the lower brainstem was examined in adult spontaneously hypertensive (SH) rats and in normotensive Wistar Kyoto (WK) controls. The specific binding of³H-WB 4101 (0.33 nM) was significantly higher in homogenates from the cerebral cortex of SH rats as compared to WK rats. No differences were detected between SH and WK rats in the specific binding of³H-spiroperidol (0.25 nM), a dopamine receptor antagonist, to membranes from the corpus striatum and the limbic forebrain. The locomotor activity was significantly higher in SH rats as compared to WK controls, in all probability due to a lack of habituation to environmental change. It is suggested that the high reactivity of SH rats is related to a dysfunction in the noradrenergic neurons in the central nervous system.     

Novel stressors affected catecholamine stores in socially isolated normotensive and spontaneously hypertensive rats

Catecholamines in some central (hypothalamus and hippocampus) and peripheral tissues (adrenal glands and heart auricles) of long-term socially isolated normotensive and spontaneously hypertensive rats exposed to novel immobilization stress were determined by a simultaneous single isotope radioenzymatic assay. Long-term isolation (21 days) produced depletion of hypothalamic norepinephrine (NE) stores and hippocampal dopamine (DA) stores in both normotensive and spontaneously hypertensive rats. Acute immobilization stress (2 h) significantly decreased NE and DA stores in hypothalamus and hippocampus of naive normotensive and spontaneously hypertensive rats controls. However, novel immobilization stress applied to normotensive rats previously subjected to long-term isolation produced no changes in catecholamine levels in hypothalamus, while resulting in somewhat higher depletion of NE stores in hypothalamus of spontaneously hypertensive rats treated in the same way. Novel immobilization stress decreased NE and DA stores in hippocampus of normotensive but was without effect on NE and DA stores of spontaneously hypertensive rats. Social isolation did not affect catecholamine stores in peripheral tissues but novel immobilization stress produced a significant decrease in catecholamine content. The results suggest that some central and peripherals tissues of spontaneously hypertensive rats and normotensive rats differ with regard to catecholamine content and that there are certain differences in their responsiveness to stress.     

Electrophysiological properties of neurons in the rostral ventrolateral medulla of normotensive and spontaneously hypertensive rats

Single unit activities were recorded from the rostral ventrolateral medulla (RVL) of pentobarbital-anesthetized normotensive Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Throughout the recording period, arterial blood pressures of WKY (mean arterial pressure, MAP = 103.1 mm Hg) and SHR (MAP = 159.2 mm Hg) remained stable at the respective basal levels. The units recorded in this study were all spontaneously active and cardiac-locked. Two types of discharge patterns, namely single and double discharges, were identified. These single and double discharge units were found to distribute randomly in RVL. In WKY, 92.6% of RVL neurons exhibited single discharges whereas in SHR, the majority (57%) of RVL neurons exhibited double discharges. The mean firing rate of single discharge units in RVL of SHR was significantly higher than that of WKY, whereas the mean firing rate of double discharge units in WKY was similar to that of SHR. About half of the units studied were also tested for antidromic collision; all units tested could be antidromically activated from the intermediolateral column (IML) of the thoracic spinal cord and the lowest threshold sites were consistently localized within IML. In both groups of rats, the axonal conduction velocity of RVL neurons showed a bimodal distribution viz. the fast and slow conducting axons. The mean conduction velocities of each of these two groups of neurons in WKY and SHR were similar. Most of the double discharge units in WKY and SHR belonged to the fast conducting type.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiovascular effects of L-glutamate and tetrodotoxin microinjected into the rostral and caudal ventrolateral medulla in normotensive and spontaneously hypertensive rats

The purpose of this study was to compare the responsiveness of the rostral and caudal ventrolateral medulla in spontaneously hypertensive (SH) and normotensive Wistar-Kyoto (WKY) rats to microinjection of L-glutamate, and to estimate tonic output of these areas by microinjecting the neurotoxin tetrodotoxin. Rats were anesthetized with 1.25 g/kg urethane s.c., implanted with arterial (femoral) and venous (femoral) catheters, artificially ventilated and paralyzed with gallamine triethiodide (10 mg/kg). Using a ventral approach to the brainstem, the mean arterial pressure and heart rate responses to microinjection (30 nl) of L-glutamate (1, 10 and 100 mM) and tetrodotoxin (10 microM) into the rostral and caudal ventrolateral medulla were compared in SH (n = 7) and WKY (n = 7) groups. Microinjection of L-glutamate into the rostral ventrolateral medulla produced equivalent increases in mean arterial pressure (maximum +33 +/- 3 and +36 +/- 6 mm Hg, SH and WKY groups respectively) and minimal changes in heart rate. Similar administration of L-glutamate into the caudal ventrolateral medulla caused decreases in mean arterial pressure and heart rate; changes in mean arterial pressure were significantly greater in the SH group than in the WKY group (-52.3 +/- 2.9 mm Hg for SH, -22.6 +/- 2.6 mm Hg for WKY). Bilateral microinjection of tetrodotoxin into the caudal ventrolateral medulla produced significantly larger increases of mean arterial pressure in WKY rats (+8 +/- 4 vs +46 +/- 8 mm Hg for SH vs WKY). These data indicate that SH rats may have a lower tonic activity of neurons in the caudal ventrolateral medulla, resulting in a lower restraining influence on sympathetic outflow in the SH rat.     

Differential effects of V2 vasopressin agonist and antagonists on blood pressure regulation in normotensive (WKY) and spontaneously hypertensive (SHR) rats.

The effects of arginine vasopressin analogs with V2 agonistic and antagonistic properties on blood pressure (BP) and heart rate (HR) were compared in conscious, spontaneously hypertensive (SHR) and normotensive (WKY) rats under resting conditions and after administration of phenylephrine (Phe) and sodium nitroprusside (SN). In WKY rats, resting BP and HR were not significantly affected during intravenous (i.v.) infusion of dVDAVP, (V2 agonist; 200 pg/kg/min), d(CH2)5 (D-Ile2,Abu4]AVP (V2 antagonist 1; weak V1 antagonist; V2/V1 ratio = 29; 0.6 microgram/kg/min), d(CH2)5[D-Ile2,Ile4,AlaNH2]AVP (V2 antagonist 2; very weak V1 antagonist; V2/V1 ratio = 83; 0.6 microgram/kg/min) and combined infusion of V2 agonist and V2 antagonist 2. Under resting conditions BP and HR were not affected in WKY by any of the treatments. In SHR rats BP and HR were significantly decreased by V2 antagonist 2 infused alone or in combination with V2 agonist. In WKY but not in SHR V2 agonist without and with prior V2 receptors blockade significantly augmented bradycardia associated with a maximum increase of the systolic blood pressure after Phe administration. Significant differences were found between SHR and WKY in SN-induced changes of HR and BP after administration of V2 agonist and antagonists. The results suggest that circulating vasopressin may modify the baroreflex by interaction with receptors which are stimulated by V2 agonist but are different from the classical V2 receptors. The study supports evidence for differential effects of vasopressin analogs on blood pressure and blood pressure-heart rate relations in WKY and SHR.     

Morphology of aortic depressor nerve myelinated fibers in normotensive Wistar-Kyoto and spontaneously hypertensive rats

Reports on the morphology of the baroreceptor terminal of spontaneously hypertensive rats (SHR) did not demonstrate any difference when compared to the axonal terminal of normotensive rats. Although several studies reporting baroreceptor terminal and blood vessel wall morphology have been carried out to better understand the baroreceptor function and resetting to hypertensive levels, there are no reports examining the morphology of the fibers of the aortic depressor nerve (ADN) in hypertensive models. Therefore, the objective of the present study was to investigate the morphological aspects of SHR ADN compared to Wistar-Kyoto (WKY) rats. Before the morphologic study, the nerves were isolated and the pressure-nerve activity curve was determined for each ADN. SHR exhibited an increase in the threshold pressure for baroreceptor activation, a rightward shift in the pressure-nerve activity curve with decreases in slope and maximum activity. Semithin (0.3 to 0.5 microm thick) sections of the proximal (close to the nodose ganglion) and distal (close to the aortic arch) segments of the ADN were analyzed by light microscopy. A morphometric study of the nerve fascicles and myelinated fibers was performed. Comparison between proximal and distal segments of the two strains revealed that the ADN of WKY rats were consistently larger. All morphometric parameters studied in myelinated fibers and their respective axons were smaller in SHR. The area of the myelin sheath was comparatively larger in WKY rats. These data show morphologic differences between the ADN of SHR and WKY rats, which may explain, at least in part, the decreased slope and maximum activity of the pressure-nerve activity curve observed with the baroreceptor resetting in SHR.     

The morphometry of consecutive segments in cerebral arteries of normotensive and spontaneously hypertensive rats

The media cross-sectional area, the media thickness, the internal radius and the ratio between media thickness and internal radius were determined in consecutive sections of extraparenchymal cerebral arteries of 7- and 12-month-old normotensive and spontaneously hypertensive rats. The study included intracranial pial and basal arteries as well as extracranial cervical arteries. In the chronically hypertensive rats the media to radius ratio was consistently higher than in normotensive rats over the entire calibre spectrum investigated (radius 5-400 micron). The increase of the ratio in the extracranial arteries of the hypertensive rats was exclusively due to a thicker media. In the basal intracranial arteries the increase of ratio was due to a thicker media and/or a smaller internal radius in 7- and 12-month-old rats with moderate hypertension (mean arterial pressure, MAP 171 +/- 8 and 177 +/- 7 mm Hg respectively). In 7-month-old rats with severe hypertension (MAP 204 +/- 11 mm Hg) the increase of ratio was mainly due to a smaller internal radius. The observed structural alterations are likely to be of hemodynamic importance.     

Carotid chemoreceptor discharge responses to hypoxia and hypercapnia in normotensive and spontaneously hypertensive rats

The carotid chemoreceptor discharge responses to hypoxia and hypercapnia were quantitatively compared between normotensive (NTR) and spontaneously hypertensive rats (SHR). For this purpose we recorded afferent mass discharges from the carotid sinus nerve (CSN) at various levels of end-tidal O2 and CO2 concentrations (FetO2, FetCO2 (%)) in the urethane-anesthetized, vagotomized and artificially ventilated rats. The CSN chemoreceptor discharge was evaluated by subtracting the small activity remaining in acute hyperoxia (chemoreceptor inactivation), which was estimated as baroreceptor in origin, from the large total CSN activity. The CSN chemoreceptor discharges at various levels of FetO2 or FetCO2 were expressed as the percent of control activity measured in normoxic and normocapnic conditions (FetO2, 15-16%; FetCO2, 4.5-5.1%). There was an exponential increase in the CSN chemoreceptor discharge as FetO2 was decreased from hyperoxic to various hypoxic levels (maximally 6%) at a maintained FetCO2 (normocapnia). The relationship between the CSN chemoreceptor discharge and the hypoxic stimulus was quantitatively assessed by the regression analysis using an exponential function. Exponential increases in the CSN chemoreceptor discharge by hypoxia and the parameters in the exponential function reflecting the sensitivity to hypoxia were significantly higher in the SHR than in the NTR, which indicated a high carotid chemoreceptor discharge response to hypoxia in the SHR. The CSN chemoreceptor discharge was increased linearly by increasing the FetCO2 from the normocapnic level up to about 10% at a maintained FetO2 (normoxia). Increases in discharge produced by severe hypercapnia were, however, much smaller than that caused by hypoxia. The slope of the CO2 stimulus-CSN chemoreceptor discharge response line was almost the same in NTR and SHR. The results demonstrated that the responsiveness of rat carotid chemoreceptor to hypoxia is augmented in the SHR. The role of carotid chemoreceptor afferents in ventilatory reflex responses to hypoxia and their alterations in the SHR are discussed.     

Differential endocannabinoid regulation of baroreflex-evoked sympathoinhibition in normotensive versus hypertensive rats

Previously, we found that endocannabinoids acting at cannabinoid 1 receptors in the nucleus tractus solitarius prolonged baroreflex inhibition of renal sympathetic nerve activity in normotensive Sprague Dawley rats. The current study investigated whether endocannabinoid signaling was altered in spontaneously hypertensive rats, a model marked by elevated sympathetic activity and depressed baroreflex responses. The effects of endocannabinoids in the nucleus tractus solitarius on baroreflex control of renal sympathetic nerve activity evoked by systemic pressor changes or by direct stimulation of nucleus tractus solitarius neurons, which produced depressor and sympathoinhibitory responses, were studied in Sprague Dawley rats, Wistar Kyoto rats, and spontaneously hypertensive rats. Evoked responses were compared before and after microinjection of AM404, which prolonged actions of endogenous endocannabinoids, or microinjection of an endocannabinoid, anandamide, into the baroreceptive region of the nucleus tractus solitarius. AM404 microinjections significantly prolonged evoked sympathoinhibition in Sprague Dawley and Wistar Kyoto rats, but had little effect in spontaneously hypertensive rats. Microinjections of anandamide prolonged sympathoinhibition in Sprague Dawley rats, with lesser effects in Wistar Kyoto rats and no effects in spontaneously hypertensive rats. Parallel studies found that density of binding sites of endocannabinoids in the nucleus tractus solitarius was significantly reduced in spontaneously hypertensive rats versus the normotensive rats. Results indicate that attenuated function of the endocannabinoid system in the nucleus tractus solitarius of spontaneously hypertensive rats resulted in less modulation of baroreflex-evoked sympathoinhibition and that reduced cannabinoid 1 receptor density could contribute to blunted baroreflex-induced sympathoinhibition and elevated sympathetic tone characteristic of spontaneously hypertensive rats.     

Regional brain concentrations of vasoactive intestinal polypeptide in normotensive Wistar-Kyoto and spontaneously hypertensive rats

The regional brain and spinal cord concentrations of vasoactive intestinal polypeptide immunoreactivity (VIP) were measured in age-matched normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SH) rats. The relative order of distribution of VIP in the WKY strain was cortex (44 pmol/g) greater than hippocampus = striatum greater than midbrain = hypothalamus greater than medulla oblongata/pons = lumbar spinal cord (SC) greater than cervical SC greater than thoracic SC (2.5 pmol/g) whereas in the SH strain this order was cortex (35 pmol/g) greater than striatum = midbrain greater than hippocampus = hypothalamus greater than medulla oblongata/pons = lumbar SC greater than cervical SC greater than thoracic SC (1 pmol/g). The VIP concentrations of the thalamus, cerebellum and pituitary were at the level of assay sensitivity (0.5 pmol/g) in both strains. In comparison to the WKY, the SH rats had significantly lower VIP levels in the hippocampus (-42%) and cervical (-46%) and thoracic (-56%) spinal cord but significantly higher levels in the midbrain (+64%).     

Inhibition of release of neurohypophysial hormones by endogenous opioid peptides in pregnant and parurient rats

Naloxone, an opiate receptor antagonist, was used to determine whether opioid peptides modulate release of oxytocin (OT) or vasopressin (AVP) in the rat after expulsion of the fetus, i.e. parturition. We measured the concentrations of AVP and OT in plasma and in the neurointermediate lobe of the pituitary of pregnant rats given naloxone (5 mg/kg, s.c.) or saline on day 20 of gestation, and on day 21 either before or during the expulsive stage of labor. Non-pregnant rats in diestrus were giben naloxone for comparison. On days 20 and 21 of gestation, before the onset of parturition, plasma [AVP] but not [OT] was elevated, compared to the non-pregnant controls. After delivery of the first two pups, plasma [OT] approximatelyy doubled, whereas plasma [AVP] remained unchanged. Blocking the action of endogenous opioid peptides with naloxone caused an elevation of plasma [OT] in pregnant animals on days 20 and 21 of gestation and during parturition. Naloxone, however, did not alter plasma [AVP] in either parturient or preparturient animals. In contrast, [AVP], but not [OT], was increased in plasma of non-pregnant rats given naloxone. The content of OT in the neuro-intermediate lobe was similar in pregnant and non-pregnant rats and was unaffected delivery of the first two pups. However, AVP content and the ratio of AVP/OT in the pituitary were lower in pregnant animals before during delivery than in the non-pregnant controls. The content of neither hormone was altered by naloxone. Thus, AVP release apparently increase and pituitary stores of this peptide are decreased by day 20 gestation, when labor has not yet begun. In contrast, OT secretion becomes elevated only during delivery. Inhibition of OT release by opioid peptides may: (1) allow preferential release of AVP during pregnancy; and (2) prevent depletion of pituitary stores of OT and neuronal fatigue during the 1–2 h period of parturition in the rat.     

Effects of colchicine on hexokinase activity in the paraventricular and supraoptic nuclei of spontaneously hypertensive and normotensive rats

The effects of intracerebroventricular (ICV) colchicine (70 micrograms per rat) on systolic pressures and levels of hexokinase activity in the hypothalamic paraventricular (PVH) and supraoptic (SON) nuclei were investigated in adult normotensive and spontaneously hypertensive rats (SHR). One day after colchicine injection, systolic pressures had dropped significantly in Sprague-Dawley (SD) rats, Wistar-Kyoto (WKY) rats, and SHR; the largest decrease was seen in SHR. Postinjection pressures in SHR were within the normotensive range. No further decreases were observed two days after injections. Quantitative analysis of hexokinase activity in control animals verified that the parvo- and magnocellular PVH (but not SON) of SHR contained significantly lower levels of hexokinase than in WKY or SD rats. Two days after colchicine injection, hexokinase activities in pPVH and mPVH were similar in all three strains. Activity had decreased significantly in SD and WKY rats. In SHR, no differences between control and postinjection values were found. Hexokinase activity in SON was significantly decreased to the same extent in all strains. As metabolic activity in the pPVH, mPVH, and SON decreased after colchicine injection in normotensive rats whereas no such decreases occurred in the pPVH and mPVH of SHR, the findings suggest that colchicine may have differential effects on the metabolic activity of specific cell groups in brain depending on the physiological state of the animal.     

Inhibition of release of neurohypophysial hormones by endogenous opioid peptides in pregnant and parturient rats

Naloxone, an opiate receptor antagonist, was used to determine whether opioid peptides modulate release of oxytocin (OT) or vasopressin (AVP) in the rat after expulsion of the fetus, i.e. parturition. We measured the concentrations of AVP and OT in plasma and in the neurointermediate lobe of the pituitary of pregnant rats given naloxone (5 mg/kg, s.c.) or saline on day 20 of gestation, and on day 21 either before or during the expulsive stage of labor. Non-pregnant rats in diestrus were given naloxone for comparison. On days 20 and 21 of gestation, before the onset of parturition, plasma [AVP] but not [OT] was elevated, compared to the non-pregnant controls. After delivery of the first two pups, plasma [OT] approximately doubled, whereas plasma [AVP] remained unchanged. Blocking the action of endogenous opioid peptides with naloxone caused an elevation of plasma [OT] in pregnant animals on days 20 and 21 of gestation and during parturition. Naloxone, however, did not alter plasma [AVP] in either parturient or preparturient animals. In contrast, [AVP], but not [OT], was increased in plasma of non-pregnant rats given naloxone. The content of OT in the neuro-intermediate lobe was similar in pregnant and non-pregnant rats and was unaffected by delivery of the first two pups. However, AVP content and the ratio of AVP/OT in the pituitary were lower in pregnant animals before and during delivery than in the non-pregnant controls. The content of neither hormone was altered by naloxone. Thus, AVP release apparently increases and pituitary stores of this peptide are decreased by day 20 of gestation, when labor has not yet begun.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dose-dependent, amphetamine-induced changes in permeability of the blood-brain barrier of normotensive and spontaneously hypertensive rats

The permeability of the blood-brain barrier to ¹³¹I-radioiodinated human serum albumin can be changed by the acute administration of amphetamine intravenously. In normotensive rats (WKY), the response was dose dependent and biphasic. The permeability was increased by doses of 7.5 mg/kg or less and the permeability was decreased by doses of 15 and 30 mg/kg. The response to amphetamine in spontaneously hypertensive rats (SHR) was quite different. The permeability of the blood-brain barrier was greater in the saline-treated spontaneously hypertensive animals than in the saline-treated normotensive animals. Doses of amphetamine to as much as 5 mg/kg caused an increase in permeability, but much less than was found in the normotensive animals. At doses of amphetamine from 7.5 to 30 mg/kg, there were no significant changes in permeability of the blood-brain barrier. There was a high correlation between the acute change in blood pressure caused by the administration of amphetamine and the change in permeability of the blood-brain barrier.