Role of endogenous brain kinins in the cardiovascular response to intracerebroventricular melittin

Intracerebroventricular infusion of the peptide melittin increases immunoreactive kinins in the cerebrospinal fluid of anesthetized dogs, probably secondary to activation of brain or cerebrospinal fluid kininogenases. Intracerebroventricular melittin also increases blood pressure and heart rate, possibly mediated by brain kinins, since intracerebroventricular bradykinin also increases blood pressure and heart rate. We tested whether the effects of centrally administered melittin on blood pressure and heart rate could be blocked by simultaneous infusion of a kinin receptor antagonist, [DArg0]Hyp3-Thi5,8[DPhe7]bradykinin, in normotensive awake rats. In the controls, intracerebroventricular infusion of kinin receptor antagonist given for 1 hour at a rate of 10 micrograms/hr blocked bradykinin-induced increases in blood pressure and heart rate by 80%. Basal blood pressure and heart rate were not affected by the kinin receptor antagonist alone. After a 30-minute infusion of melittin (8 micrograms/30 min), cerebrospinal fluid kininogenase activity (n = 17) rose from 0.13 +/- 0.05 to 0.43 +/- 0.1 ng/ml/min (p less than 0.02). Although cerebrospinal fluid kinins increased from below sensitivity (0.02 ng/ml, n = 12) to 0.19 +/- 0.1 ng/ml (n = 17), this change was due to drastic increases in three rats, whereas in 12 of them kinins were below sensitivity. Incubation of bradykinin (10 ng) with 0.1 ml rat cerebrospinal fluid for 5 minutes destroyed 70% of kinins, suggesting that rapid destruction may have made detection of increased CSF kinins difficult.(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of vasopressin in the cardiovascular response to stimulation of the locus coeruleus

Hypothalamic vasopressin synthesizing nuclei (paraventricular and supraoptic) send vasopressin-containing projections to a number of neural target areas thought to be involved in cardiovascular regulation. One area known to receive vasopressinergic projections from the paraventricular nucleus is the pontine nucleus locus coeruleus. To examine the possible functional participation of vasopressin in central cardiovascular regulation, we examined mean arterial pressure (millimeters of Hg) and heart rate (beats per min) responses to electrical stimulation of the locus coeruleus in conscious, unrestrained vasopressin-deficient Brattleboro rats homozygous for diabetes insipidus (DI rats) and long Evans (LE) rats. Rats received chronic arterial and venous catheters and bipolar stimulating electrodes 3-5 days before experiment. Stimulation of the locus coeruleus (100 microA, 10-40 Hz) produced frequency-dependent increases in mean arterial pressure and heart rate in LE and DI, but the responses were significantly less in the latter group. The deficiency in mean arterial pressure and heart rate responses to locus coeruleus stimulation in DI rats was found to be centrally mediated in that responses to peripherally administered phenylephrine were the same as those for LE rats. Ganglionic blockade significantly attenuated responses to locus coeruleus stimulation in LE rats but had little effect in DI rats. Pretreatment of DI rats with chronic intracerebroventricular infusion of vasopressin (osmotic minipump) at a dose that had no effect peripherally increased the mean arterial pressure and heart rate responses to locus coeruleus stimulation. Our results suggest that vasopressin acts in the region of the locus coeruleus to exert a central action on sympathetic outflow.     

Release of oxytocin and vasopressin by intracerebroventricular vasoactive intestinal polypeptide

Vasoactive intestinal polypeptide (VIP)ergic nerves innervate both the neurohypophysis and the hypothalamus. To test the hypothesis that VIP is a releasing factor for neurohypophyseal hormones, rats were given intracerebroventricular (icv) infusions of VIP in doses varying from 0.3 pmol/kg.min to 3 nmol/kg.min for 5 min (0.001-10 micrograms/rat). Serial blood samples were drawn from the vena cava for measurement of oxytocin (OT), vasopressin (AVP), and VIP by RIA. After the VIP infusions mean plasma OT and AVP levels rose in a dose-dependent manner; the rise was significant for both hormones at the dose of 300 pmol/kg.min. Peak levels after infusion of 3 nmol/kg.min were greater for OT than AVP [96.1 +/- 14.7 vs. 33.9 +/- 9 microU/ml (mean +/- SE); n = 6]. In addition, the concentration of plasma OT increased more promptly than that of AVP. Plasma OT was significantly raised over control values at 5 min, whereas plasma AVP was not increased until 15 min after the VIP infusion began. The concentration of VIP in peripheral plasma rose somewhat after icv infusions (maximum, 300 pmol/liter 30 min after 10 micrograms/rat), but the rise was only 5% of that observed after systemic infusions of equimolar doses of VIP (maximum, 6000 pmol/liter 5 min after 10 micrograms/rat). Peak plasma OT levels after administration of 3 nmol/kg.min VIP were significantly higher after icv than after systemic infusion of the same dose of VIP reported previously. Intravenous injection of 0.5 ml VIP antiserum with a binding capacity of VIP of 2.3 micrograms/ml before the icv administration of VIP (1 microgram/rat) did not prevent the VIP-induced rise in plasma OT and AVP. These observations suggest a central site of action for VIP in OT and AVP release, probably in the hypothalamus. The results are in harmony with the hypothesis that endogenous VIP is a physiological regulator of OT and AVP release in rats.     

Central catecholamines and alpha-adrenoceptors in acute hypertension induced by intracerebroventricular hypertonic saline

We measured the tissue content of catecholamines and the numbers and affinities of alpha 1- and alpha 2-adrenergic receptors in specific areas of the hypothalamus and medulla oblongata of rats treated with intracerebroventricular microinjection of hypertonic saline, in comparison to controls treated with an equal volume of iso-osmolar dextrose solution. Rats given 20 microliter of 4% NaCl into the lateral ventricle showed an average rise in blood pressure of 14 +/- 2 mmHg and a decrease in heart rate of 63 +/- 11 beats/min (P less than 0.001 for both), associated with dopamine suppression in the anteroventral area of the third ventricle (AV3V) and increased concentrations of dopamine in the C2 region of the medulla and of epinephrine in the area postrema. Affinities of medullary alpha 2-adrenoceptors were decreased in the saline-treated rats, whereas the number of receptors tended to be higher. It is suggested that sodium may produce its pressor effect by diminishing the affinity of central alpha 2-adrenoceptors for neurotransmitters, resulting in disinhibition of certain sympathoinhibitory neurons and increased sympathetic outflow.     

Role of intracerebral angiotensin receptors in the regulation of vasopressin release and the cardiovascular system

In order to investigate the physiological role of the brain renin-angiotensin system in the regulation of vasopressin (ADH) release, angiotensin II (Ang II, 10 ng/kg/min) or 1-Sar-8-Ile-Ang II (50 ng/kg/min), an Ang II antagonist, was administered intracerebroventricularly to dogs (n = 42) anesthetized with urethane and chloralose after morphine sedation. The effects of the intravenous infusion of either 0.15 M or 2.5 M NaCl (0.1 ml/kg/min, 75 min) were also studied. In control dogs, artificial cerebrospinal fluid (ACSF) was administered at a rate of 10 microliter/min for 105 min. ACSF given intracerebroventricularly plus 0.15 M NaCl given intravenously did not affect ADH release, but 2.5 M NaCl given intravenously raised the plasma ADH level in parallel with the rise in plasma osmolality. Heart rate and blood pressure did not change significantly in ACSF along with 0.15 M NaCl, but heart rate increased significantly in ACSF along with 2.5 M NaCl. Ang II along with 0.15 M NaCl significantly raised plasma ADH and decreased heart rate without any changes in blood pressure. Ang II along with 2.5 M NaCl brought about a significant rise in plasma ADH level, arterial blood pressure, heart rate, and plasma osmolality. But simultaneous application of Ang II and 2.5 M NaCl did not result in a larger rise in plasma ADH than that expected from the effects of the two stimulations given separately. Namely, Ang II did not potentiate ADH release elicited by osmotic stimulation. Ang II antagonist given intracerebroventricularly neither affected ADH release and the cardiovascular system in 0.15 M NaCl nor inhibited ADH release in response to osmotic stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Renal response to graded intravenous hypertonic NaCl infusion in healthy and hypertensive subjects:dose-related impairment in distal NaCl reabsorption

The effects of graded acute intravenous hypertonic NaCl loads on the baseline relationship between osmolal clearance and free water reabsorption established during high NaCl dietary intake and on the fractional excretion of various ions were investigated in 15 healthy subjects and in 12 “normal renin” essential hypertensive patients. No significant influence on the baseline relationship could be demonstrated after a moderate NaCl load in the healthy subjects, while free water reabsorption was depressed by the same intervention in the hypertensive patients. High NaCl loads induced depression of free water reabsorption in a dose-related fashion in both groups. No difference was found in phosphaturia between the groups after the same NaCl load as well as in the healthy persons after different NaCl loads, supporting the contention that the observed differences in free water reabsorption were not due to changes in the proximal nephron. It was concluded that: (1) impaired NaCl reabsorption in Henle's loop (depression of free water reabsorption) may also occur in response to acute NaCl loadings in healthy subjects, and (2) “exaggerated natriuresis” is the consequence of a normal renal response (imparied NaCl transport in Henle's loop) to a certain degree of volume expansion reset abnormally to a lower level in hypertensive patients.     

The cardiovascular responses to sequential inhibition of alpha-adrenoceptors, the renin-angiotensin system and vasopressin in rats with adrenal regeneration hypertension

The cardiovascular responses to selective alpha 1- and alpha 2-adrenoceptor antagonism (with prazosin and idazoxan, respectively) were assessed in rats 4 weeks after unilateral nephro-adrenalectomy, contralateral adrenal enucleation and the provision of a 1% NaCl solution as drinking fluid (AEN rats) and in sham-operated (SON) rats. Measurements were made between 0700 and 1000 h and between 1400 and 1700 h, since we have previously shown that resting blood pressures (BPs) in AEN rats are higher in the morning than in the afternoon. Following prazosin administration (morning or afternoon), BP fell to similar levels in both SON and AEN rats. Idazoxan, given 20 min after the start of prazosin infusion, caused similar transient falls in BP in all four groups of rats. Following the subsequent additional antagonism of angiotensin II (Ang II) production (with captopril) and vasopressin (V1) receptors [with d(CH2)5DAVP], BP in AEN rats studied in the morning was higher than in SON rats at that time of day, and higher than in AEN rats studied in the afternoon. These findings suggest than an additional underlying mechanism capable of increasing BP exists in AEN rats studied in the morning.     

Role of the serotonergic nervous system in hemodynamic and vasopressin responses to centrally administrated angiotensin-II in spontaneously hypertensive rats

The purpose of the study is to investigate the role of the serotonergic nervous system in centrally administrated angiotensin II (A-II) mediated hemodynamic as well as vasopressin (AVP) responses. Eight-week-old male SHR and age-matched Wistar Kyoto rats (WKY) were used and the experiment was performed in the conscious state. In protocol 1, after resting observation of 30 minutes 10ng of A-II was given intracerebroventricularly (i.c.v.). This was followed by i.c.v. injection of 1 microgram of 5-HT2 receptor antagonist, xylamidine, 50 minutes later; then 10ng of i.c.v. A-II was repeated after 10 minutes (SHR: n = 7, WKY: n = 10). In protocol 2, plasma vasopressin (AVP) was measured in the following groups. In one group, 1.3ml of blood was sampled from the carotid cannula after resting observation, and the same amount of blood from an age-matched donor rat of the same strain was transfused immediately. Two hours later, 10ng of A-II was given i.c.v., and blood was sampled again after 1 minute (SHR: n = 7, WKY: n = 12). In another group, 1 microgram of xylamidine was given i.c.v. and was followed by 10ng of A-II 10 minutes later; then blood was collected after 1 minute (SHR: n = 8, WKY: n = 13). In protocol 1, resting MAP were 144 +/- 6mmHg in SHR and 99 +/- 2mmHg in WKY. I.c.v. A-II elicited a consistent pressor response in both SHR and WKY, but the response was significantly larger in SHR than that in WKY, +45 +/- 3 and +37 +/- 1mmHg, respectively. Xylamidine had no effect on MAP, and repeated A-II produced significant pressor responses. However, the responses were significantly smaller in both SHR (+36 +/- 3mmHg) and WKY (+25 +/- 1mmHg) as compared with those to initial A-II injection. In protocol 2, resting AVP were similar in SHR (1.5 +/- 0.2pg/ml) and in WKY (1.6 +/- 0.1pg/ml). However, after i.c.v. A-II injection, AVP became higher in SHR (131 +/- 14pg/ml) than in WKY (64 +/- 6pg/ml). AVP after A-II injection with xylamidine pretreatment were similar in SHR (48 +/- 6pg/ml) and in WKY (45 +/- 4pg/ml). Since the responses of both MAP and AVP to i.c.v. A-II were larger in SHR, and the responses were effectively suppressed by S2 receptor antagonists, the central serotonergic nervous system may play an important role in the hemodynamic as well as AVP responses to i.c.v. A-II administration.     

Sexual dimorphism in vasopressin and cardiovascular response to hemorrhage in the rat

There is evidence for sex-related differences in the cardiovascular actions of vasopressin. Furthermore, receptors for the gonadal steroid hormones are located in centers in the brain involved in the control of vasopressin release and in cardiovascular regulation. We have, therefore, examined the effects of hemorrhage on mean arterial blood pressure, the plasma vasopressin concentration, and plasma renin concentration in conscious male and female rats. In preliminary experiments, no differences were found in blood and plasma volumes with respect to either sex or phase of the estrous cycle. In separate experiments, rats were subjected to two hemorrhages of 10% of blood volume, separated by an interval of 15 minutes. There were no substantial gender- or cycle-related differences in the ability of hemorrhaged rats to maintain mean arterial blood pressure or increase plasma renin concentration. The increase in plasma vasopressin concentration was greater in proestrous females than in males after the first hemorrhage and in diestrous, proestrous, and metestrous females than in males after the second hemorrhage. Pretreatment with a V1-receptor antagonist was without statistically significant effect on the mean arterial blood pressure responses in males, but it impaired blood pressure compensation in females. There are, then, gender- and cycle-related differences in vasopressin responses to hemorrhage, and vasopressin appears particularly important for blood pressure compensation to hemorrhage in female rats.     

Questionnaire responses that predict airway response to hypertonic saline

BACKGROUND: Airway hyperresponsiveness to hypertonic saline (HS) is associated with airway inflammation. We investigated if responsiveness to HS was predicted by asthma symptoms in the last 3 months. OBJECTIVES: To investigate if responsiveness to HS can be estimated by questionnaire items investigating asthma symptoms of the last 3 months. METHODS: Six hundred and four patients with physician-diagnosed asthma being assessed for asthma severity were studied. Bronchial provocation with 4.5% saline was performed, and a questionnaire was administered. The response to 4.5% saline was reported as the provoking dose to cause a 15% fall in the forced expiratory volume in 1 s FEV(1) (PD(15)) and the response-dose ratio (RDR). RESULTS: Based on the GINA guidelines, asthma severity was intermittent in 497 patients, mild in 107 patients, moderate in 3 patients and severe in 1 patient. A PD(15) to 4.5% saline was recorded in 234 of the 604. Questions on self-recognition of asthma, dust as a trigger, food as a trigger, and frequency of bronchodilator use were significant predictors for a PD(15), and currently taking steroids decreased the likelihood of a positive response to 4.5% saline. Using a multiple-linear regression model, a difference in the RDR could be calculated between those who answered positively compared with the reference group, who answered negatively. This difference could be used as a guide for predicting abnormal reactivity. An increase in RDR in response to 4.5% saline, compared with the reference group, was demonstrated in the presence of self-recognition of asthma severity, dust and cats as a trigger or use of bronchodilator during sleep hours. CONCLUSIONS: Because of the high positive predictive value of HS for identifying patients with asthma it might be that the need for bronchodilator use at night not only predicts airway hyperresponsiveness to HS, it also could reflect the severity of asthma.     

Adrenocorticotropin and cortisol responses to vasopressin during pregnancy.

CRH is secreted by the placenta into the maternal and fetal circulation during pregnancy in humans and non-human primates. ACTH and cortisol responses to exogenous CRH are blunted during pregnancy. In the present study we examined the pituitary-adrenal response to another corticotropin releasing factor, vasopressin. Studies were performed in chronically catheterized female baboons moving freely in their home cages; 13 studies were performed in 4 pregnant animals, and 8 studies were performed in 6 nonpregnant animals. Vasopressin was administered iv in 2 doses (0.3 and 3.0 U), and plasma samples were obtained for CRH, ACTH, and cortisol measurements. Results are expressed as the mean +/- SEM. Baseline plasma CRH was 240 +/- 20 pmol/L in the pregnant animals and unmeasurable (less than 20) in the nonpregnant animals. In the pregnant animals, ACTH concentrations rose from a baseline of 6.4 +/- 1.3 pmol/L to 10.1 +/- 0.4 after 0.3 U vasopressin and to 24.9 +/- 5.2 after 3.0 U vasopressin. In the nonpregnant animals, ACTH levels were 5.8 +/- 1.3 at baseline, 6.7 +/- 1.3 after the 0.3-U dose, and 14.6 +/- 2.4 after the 3.0-U dose. The peak ACTH response after each dose of vasopressin was higher in the pregnant animals than in the nonpregnant animals (P less than 0.05). The baseline cortisol level in the pregnant animals was 960 +/- 80 nmol/L and rose to 1370 +/- 110 and 1535 +/- 165 after the 2 doses of vasopressin, respectively. The baseline cortisol concentration in the nonpregnant animals was 910 +/- 86 nmol/L. The cortisol level was 990 +/- 75 after the 0.3-U vasopressin dose and 1380 +/- 140 after the 3.0-U dose. The peak cortisol response after the 0.3-U dose was significantly higher in the pregnant animals (P less than 0.02), while the peak cortisol responses after the 3.0-U dose were similar in the 2 groups of animals. In a single animal, vasopressin was administered sequentially at 4 gestational ages during pregnancy and then 2 times in the postpartum period. The ACTH response to vasopressin increased as pregnancy progressed and then decreased in the postpartum period. In summary, the ACTH and cortisol responses to 0.3 and 3.0 U vasopressin, iv, are enhanced during pregnancy in the baboon, although the responses to exogenous CRH are blunted during gestation. We conclude that the chronic placental CRH stimulation of the pituitary-adrenal axis during pregnancy leads to an enhanced response to vasopressin and a down-regulation of the response to exogenous CRH.     

Influence of intravenous and intracerebroventricular vasopressin on baroreflex control of renal nerve traffic

We performed experiments in alpha-chloralose-anesthetized rabbits with vagi sectioned, to determine the influence of intravenous and intracerebroventricular vasopressin on arterial baroreflex control of renal nerve activity. Arterial baroreflex control of renal nerve activity was assessed during phenylephrine-induced increases and nitroglycerin-induced decreases in arterial pressure. Intravenous vasopressin (4 and 40 mU over 1 minute) reduced basal renal nerve activity (from 149 +/- 14 to 101 +/- 13 and 28 +/- 13 impulses/sec) without changing arterial pressure and reduced the sensitivity of the arterial baroreflex control of renal nerve activity. This effect was reversed by vasopressin antagonist (d(CH2)5[Tyr(Me)2]AVP) which blocks vasoconstrictor effects of vasopressin. Intracerebroventricular vasopressin (4, 40, or 400 mU) did not alter basal renal nerve activity or arterial pressure but increased the sensitivity of baroreflex control of renal nerve activity. This effect was not blocked by the vasopressin antagonist. The influence of intravenous vasopressin on basal renal nerve activity was not altered by sinoaortic baroreceptor denervation. In contrast, the inhibitory influence of intravenous vasopressin on lumbar sympathetic nerve activity was abolished by sinoaortic denervation. Finally, intravenous vasopressin inhibited renal nerve activity (by 43 +/- 5%) in six rabbits with spinal cord transection. This effect was abolished by the vasopressin antagonist. We draw the following conclusions from these data: (1) intravenous and intracerebroventricular vasopressin have different effects on basal and baroreflex control of renal nerve activity; (2) these effects are mediated by different vasopressin receptors; (3) the effects of intravenous vasopressin on basal renal nerve activity are not baroreflex dependent, and appear to be mediated by spinal or, possibly, ganglionic mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of vagosympathetic fibers in the control of adrenocorticotropic hormone, vasopressin, and renin responses to hemorrhage in fetal sheep

Hemorrhage stimulates endocrine and cardiovascular reflex responses that are appropriate for returning blood volume and pressure to prehemorrhage levels. Fetal sheep respond to hemorrhage with increases in plasma adrenocorticotropic hormone (ACTH), cortisol, and vasopressin concentrations and plasma renin activity, but little is known about the afferent limb of the reflex(es) controlling these responses. Fetal sheep between 128 and 133 days' gestation were chronically prepared with vascular catheters. Five fetal sheep were subjected to bilateral section of the cervical vagosympathetic trunks; six fetal sheep were not vagotomized. Four to six days after surgery, the fetuses were subjected to withdrawal of 10 ml of blood every 10 minutes for 2 hours (130 ml total). Vagotomized fetal sheep responded to the hemorrhage with a greater decrease in central venous pressure than the intact fetuses and a slower restitution of fluid to the vascular space (estimated to be 17% of the hemorrhage volume in 2 hours) than the intact fetuses (estimated to be 28% of the hemorrhage volume in 2 hours). Both groups of fetuses, however, responded to the hemorrhage with increases in fetal plasma ACTH, cortisol, and vasopressin concentrations and plasma renin activity that were not significantly different. A posteriori analysis of the data by correlation analysis revealed that the fetal ACTH, vasopressin, and renin responses to the hemorrhage were more highly correlated to the changes in fetal arterial pH than to changes in fetal mean arterial pressure or central venous pressure. The results suggest that the ACTH, vasopressin, and renin responses to hemorrhage in the fetus be mediated by chemoreceptors, not by cardiovascular mechanoreceptors.(ABSTRACT TRUNCATED AT 250 WORDS)     

Naloxone does not improve cardiovascular or blunt vasopressin responses in spontaneously hypertensive rats following graded hemorrhage

The effects of continuous intravenous infusion of naloxone or vehicle on the blood pressure and vasopressin responses to step-wise hemorrhage were examined in conscious, age-matched spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto rats (WKY). Step-wise hemorrhage progressively lowered blood pressure and increased plasma vasopressin levels in both SHR and WKY. The WKY were relatively resistant to the hypotensive effect of hemorrhage. No significant differences were noted in blood pressure responses between naloxone-treated and vehicle-treated SHR while naloxone treatment attenuated hypotension only slightly in WKY. Plasma vasopressin levels were also elevated by naloxone treatment in SHR following a nonhypotensive hemorrhage equivalent to 0.5% of body weight. However, no differences were observed between plasma vasopressin levels in naloxone-treated and vehicle-treated SHR at greater degrees of hemorrhage. In addition, plasma vasopressin levels were similar at all times in hemorrhaged WKY, regardless of treatment. Plasma vasopressin levels were increased by naloxone in both time-control SHR and WKY. The data demonstrate that naloxone-sensitive systems exert only minimal effects on the immediate cardiovascular responses to hypovolemia in normotensive rats and no measurable effects in SHR. It does appear that naloxone-sensitive mechanisms contribute a small, but significant, tonic inhibitory influence over vasopressin secretion in both normotensive and hypertensive rats under basal conditions and in SHR in response to a small reduction in blood volume.     

Effect of dehydration on cardiovascular responses and electrolytes after hypertonic saline/dextran treatment for moderate hemorrhage.

STUDY OBJECTIVE: To determine if hypertonic saline/dextran (HSD) is effective in treating hemorrhage in the presence of dehydration. DESIGN: After surgical preparation, swine were euhydrated or dehydrated for 24 or 48 hours. Animals were bled 25 mL/kg over 60 minutes and treated with HSD. SETTING: Laboratory. PARTICIPANTS: Seventeen immature Yorkshire pigs. INTERVENTIONS: 4 mL/kg HSD (7.5% NaCl in 6% dextran-70) administered over one minute. MEASUREMENTS AND MAIN RESULTS: All euhydrated animals survived; 100% of the pigs survived 180 minutes after treatment. Two animals dehydrated for 24 hours and three animals dehydrated for 48 hours died within three hours of HSD treatment. In all groups, plasma potassium was reduced significantly and equally; cardiac output was increased; mean arterial pressure rose rapidly within first five minutes, but was sustained only in euhydrated animals; hematocrit, hemoglobin, and plasma total protein levels were reduced; and plasma glucose increased with persistent between-group differences. RESULTS: HSD immediately rectified the decreases in mean arterial pressure and cardiac output incurred during hemorrhage; over time, however, the improvement in pressure was not sustained in dehydrated pigs. Parallel increases in plasma osmolality and sodium concentrations were offset by the initial group differences resulting from dehydration. CONCLUSION: Dehydration does not compromise the efficacy of HSD as a resuscitation treatment for hemorrhagic shock.     

Corticotrophin and vasopressin responses to metoclopramide in patients with hypothalamic amenorrhoea

OBJECTIVE  A dopamine (DA) antagonist, metoclopramide, stimulates ACTH secretion in some women with hypothalamic amenorrhoea (HA) but not in normal women. Metoclopramide may stimulate ACTH secretion by decreasing dopaminergic inhibition of ACTH release. Furthermore, metoclopramide stimulates AVP secretion, and AVP is a stimulator of ACTH. Therefore, AVP may also be involved in the ACTH responses to metoclopramide. The relation between AVP and ACTH responses to metoclopramide were evaluated in normal women and women with HA to obtain more insight into the role of DA in the regulation of ACTH and AVP secretion.
DESIGN  ACTH, cortisol and AVP levels were measured before and after the administration of metoclopramide in 11 normal women during the early follicular phase and 12 women with HA.
MEASUREMENTS  ACTH was measured by immunoradiometric assay. AVP and cortisol were measured by radioimmunoassay.
RESULTS  The administration of metoclopramide significantly increased circulating levels of ACTH and cortisol in the women with HA, but not in the normal women. It increased AVP levels both in the normal women and in the women with HA. The incremental AVP response to metoclopramide was not significantly different between the two groups of women.
CONCLUSION  The effect of metoclopramide on AVP secretion may not be dependent on central dopaminergic activity, and the ACTH and cortisol responses to metoclopramide in the women with hypothalamic amenorrhoea are not accounted for by the augmented AVP response to metoclopramide.     

The response of arginine vasopressin to intravenous ethanol and hypertonic saline in man: the impact of aging

The effect of age on the hypothalamic-hypophyseal-renal axis in normal man was determined by assaying plasma arginine vasopressin (AVP) responses to inhibitory and to secretory stimuli. Nine young (21-49 years) and 13 old (54-92 years) subjects received IV ethanol (375 mg/m2 per min). AVP levels fell progressively during the infusion in the young group, but fell for only 30 min in the old group and then rose paradoxically despite the continuing increase in blood ethanol. Eight young (22-48 years) and 8 old (52-66 years) men were provided identical osmolal loads by a 2-hour IV infusion of 3% NaCl at 0.1 ml/kg per min. Serum AVP rose 2.5 times the baseline in the young and 4.5 times the baseline in the old men despite identical free water clearances. Osmoreceptor sensitivity (the slope of AVP on osmolality) was greater in the old subjects. The heightened sensitivity to hyperosomolality helps examine the paradoxical response to ethanol, since osmolality increased during that time. This increased AVP response may severe to compensate for the reduced renal ability to conserve salt and water in aging man.     

Differential responses of plasma oxytocin and vasopressin to dehydration in non-stressed sheep

Group housed, castrated rams (N = 10) were studied over a 2 day period. Water was available ad libitum during day 1 (control) but was withheld throughout day 2 (experimental). On both days, blood was collected by jugular venepuncture at 10.30 h, and then again 2, 4, 6 and 24 h later. Plasma samples were analysed by radioimmunoassay for arginine vasopressin (AVP), oxytocin and cortisol content and measurements were also made of the haematocrit and plasma osmolality and electrolyte (Na+, Cl-) concentrations. After 24 h water deprivation there was a significant increase in plasma AVP levels but no changes in oxytocin or cortisol concentrations. Dehydration also significantly depressed the haematocrit and increased plasma osmolality and electrolyte concentrations.