Joan Y. Summy-Long

Central inhibition of nitric oxide synthase preferentially augments release of oxytocin during dehydration

Intracerebroventricular (i.c.v.) administration of NG-monomethyl-L-arginine monoacetate (NMMA; 500 micrograms; 402 mM) and NG-nitro-L-arginine methyl ester (NAME; 270 micrograms; 200 mM), inhibitors of nitric oxide synthase, enhanced the rise in oxytocin but not vasopressin levels in plasma of conscious rats following 24 h of water deprivation. This effect of NMMA occurred by 10 min after administration, reached its peak at 15 min and decreased by 20 min. Daily administration of lower doses (50 micrograms and 0.5 microgram/5 microliter, i.c.v.) of another inhibitor of nitric oxide synthase, NG-nitro-L-arginine, just before and after 24 h of water deprivation and in control animals treated similarly were without effect on either vasopressin or oxytocin levels. Nitric oxide, therefore, attenuates preferentially the release of oxytocin during dehydration.

Induced abortion as an independent risk factor for breast cancer: a comprehensive review and meta-analysis.

STUDY OBJECTIVE: To ascertain, from the published reports to date, whether or not a significantly increased risk of breast cancer is specifically attributable to a history of induced abortion, independent of spontaneous abortion and age at first full term pregnancy (or first live birth); to establish the relative magnitude of such risk increase as may be found, and to ascertain and quantify such risk increases as may pertain to particular subpopulations of women exposed to induced abortion; in particular, nulliparous women and parous women exposed before compared with after the first full term pregnancy. INCLUDED STUDIES: The meta-analysis includes all 28 published reports which include specific data on induced abortion and breast cancer incidence. Since some study data are presented in more than one report, the 28 reports were determined to constitute 23 independent studies. Overall induced abortion odds ratios and odds ratios for the different subpopulations were calculated using an average weighted according to the inverse of the variance. An overall unweighted average was also computed for comparison. No quality criteria were imposed, but a narrative review of all included studies is presented for the readers use in assessing the quality of individual studies. EXCLUDED STUDIES: All 33 published reports including data on abortion and breast cancer incidence but either pertaining only to spontaneous abortion or to abortion without specification as to whether it was induced or spontaneous. These studies are listed for the readers information. RESULTS: The overall odds ratio (for any induced abortion exposure; n = 21 studies) was 1.3 (95% confidence interval of 1.2, 1.4). For comparison, the unweighted overall odds ratio was 1.4 (1.3,1.6). The odds ratio for nulliparous women was 1.3 (1.0,1.6), that for abortion before the first term pregnancy in parous women was 1.5 (1.2,1.8), and that for abortion after the first term pregnancy was 1.3 (1.1,1.5). CONCLUSIONS: The results support the inclusion of induced abortion among significant independent risk factors for breast cancer, regardless of parity or timing of abortion relative to the first term pregnancy. Although the increase in risk was relatively low, the high incidence of both breast cancer and induced abortion suggest a substantial impact of thousands of excess cases per year currently, and a potentially much greater impact in the next century, as the first cohort of women exposed to legal induced abortion continues to age.

A functional role for opioid peptides in the differential secretion of vasopressin and oxytocin

The presence of opioid peptides and opiate receptors in the hypothalamo-neurohypophysial system, as well as the inhibitory effects of enkephalins and beta-endorphin on release of oxytocin and vasopressin have been well documented. The physiological importance of opioid peptides in this classical neurosecretory system, however, has remained illusive. In the present study we tested the effects of naltrexone on the plasma concentrations of oxytocin and vasopressin during dehydration, hemorrhage and suckling in the conscious rat. We obtained evidence supporting the hypothesis that opioid peptides inhibit oxytocin release and thereby promote the preferential secretion of vasopressin when it is of functional importance to maintain homeostasis during dehydration and hemorrhage. Our data support the concept that the coexistence of a neuromodulator and a neurohormone in the same neuron, as demonstrated for vasopressin with dynorphin or leucine-enkephalin, serves to regulate the differential release of two biologically different, yet evolutionarily-related, neurohormones, e.g. oxytocin and vasopressin, from the same neuroendocrine system.

The role of angiotensin in thirst

Abstract A relatively large literature has described the motivated drinking behavior produced by angiotensin, which occurs even in normally hydrated animals. Many investigations have attempted to relate angiotensin to a “regulatory” thirst drive, i.e., drinking in response to an osmotic or volume stimulus. A review of this literature is difficult because there are unclarities in various aspects of regulatory thirst. Therefore, this review is divided into two sections. The first section briefly discusses the nature and location of receptors and anatomic sites for osmotic and volume thirst and some methodological considerations. The second section describes angiotensin thirst and its potential significance.

Effects of centrally administered endogenous opioid peptides on drinking behavior, increased plasma vasopressin concentration and pressor response to hypertonic sodium chloride

Intracerebroventricular (i.v.t.) administration of beta-endorphin or leucine5-enkephalin inhibited drinking behavior, the pressor response and increased plasma vasopressin concentration stimulated by an acute elevation in CSF sodium chloride concentration (10 microliter, 1 M NaCl i.v.t.). These effects of endogenous opioid peptides were prevented by naloxone, indicating opiate receptors were required for the biologic response. Drinking behavior associated with regulatory stimuli operant during dehydration was also inhibited by opioid peptides. beta-Endorphin (i.v.t.) delayed the onset and/or reduced the volume of water consumed in response to hypertonic sodium chloride (relative cellular dehydration), polyethylene glycol (hypovolemia) and food-associated drinking behavior. Inhibition of drinking did not appear related to sensory-motor dysfunction as another motivated behavior, eating (onset, amount consumed) was unaffected by beta-endorphin. It is concluded from these results that centrally administered endogenous opioid peptides inhibit sodium chloride-stimulated cerebral mechanisms affecting blood pressure and hydration.

Enkephalin inhibition of angiotensin-stimulated release of oxytocin and vasopressin

The effect of leucine5 -enkephalin on angiotensin II (AII)-stimulated release of oxytocin and vasopressin (VP) was investigated in the conscious male rat. Changes in the plasma concentration ([]) of both oxytocin and VP were measured in animals: (1) 60 s after intracerebroventricular (i.v.t.) administration of either artificial cerebrospinal fluid (CSF) or CSF with AII (10, 50, 100 ng/5 microliter); (2) 30, 60, 90 and 300 s after single injection of AII (50 ng/5 microliter; i.v.t.) or CSF and (3) 60 s after AII (50 ng/5 microliter) or CSF in animals pretreated with leucine5 -enkephalin (100 ng/5 microliter; i.v.t.) or CSF (5 microliter). Oxytocin and VP were quantified by radioimmunoassay and values corrected for 100% recovery. The development of a sensitive radioimmunoassay for oxytocin is described. The antiserum for oxytocin enabled detection of greater than or equal to 0.8 pg/ml oxytocin with cross-reactivity of 0.01% with arginine vasopressin and 0.10% with arginine vasotocin. The inter- and intra-assay coefficients of variation were 3-9% and 3.2%, respectively. The hypotheses being tested were that i.v.t. injection of AII stimulates release of both neurohypophysial hormones non-selectively and that leucine5 -enkephalin inhibits both AII-stimulated oxytocin and VP release. Angiotensin II at doses ranging from 10 to 100 ng/5 microliter, i.v.t. increased the plasma concentration of both oxytocin and VP. Plasma levels of both neurohypophysial hormones were elevated 30 s after AII administration i.v.t. and remained elevated 300 sec later.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin and thirst: Studies with a converting enzyme inhibitor and a receptor antagonist

Abstract Although exogenous angiotensin is recognized as a potent dipsogen, the participation of endogenous angiotensin in thirst has not been well established. To investigate this question, we produced thirst in rats by relative cellular dehydration (hypertonic NaCl injection), or hypovolemia (hyperoncotic polyethylene glycol injection). An angiotensin receptor antagonists (sar(1)-ala(8)- angiotensin II, P-113), or a converting enzyme inhibitor (SQ, 20, 881, SQ) given to thirsty rats by intracerebroventricular (IVT) or peripheral routes. P-113 infused i.v. (10 μg/kg/min) or injected IVT (10 μg) did not alter the drinking response to either thirst stimulus. The latter treatment reduced the drinking response to 50 ng of IVT angiotensin II (p

Influence of Adrenergic Blocking Drugs on Central Angiotensin Effects

The central effects of angiotensin in unanes thetized rats were studied before and after administration of adrenergic blocking drugs. Intraventricular injections of prevented angiotensin-induced drinking, sympathetic stimulation, and vasopressin release. Administration Phentolamine of various β-adrenergic blocking drugs, either intraarterially or intraventricularly, did not alter central angiotensin activity in a manner which could be correlated with β-adrenergic blockade. Local anesthetics inhibited central angiotensin pressor and drinking effects. Centrally administered phentolamine or tetracaine appear to be useful tools for further studies of the actions of angiotensin on the central nervous system.

Central inhibition of nitric oxide synthase attenuates water intake but does not alter enhanced glucose utilization in the hypothalamo-neurohypophysial system of dehydrated rats

I.c.v. administration of a nitric oxide (NO) synthase inhibitor (NG-monomethyl-L-arginine, NMMA, 500 micrograms/5 microliters) to conscious rats deprived of water for 24 h attenuated drinking and decreased glucose utilization in the subfornical organ and median preoptic nucleus. NMMA did not alter the enhanced glucose utilization in the hypothalamo-neurohypophysial system (HNS) of dehydrated rats, although it has been shown to increase, selectively, oxytocin (OT) secretion [18]. This suggests that NO may act in the neural lobe to inhibit OT secretion and promote the preferential release of vasopressin during dehydration. This effect is similar to the blockade of endogenous opiate receptors by naloxone.

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 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)