Monoclonal antibodies specific for rat relaxin. VIII. Passive immunization with monoclonal antibodies throughout the second half of pregnancy reduces water consumption in rats.

Zhao, Shuangping; Malmgren, Carolina; Shanks, R.D.; Sherwood, O. D.

doi:10.1210/endo.136.5.7720635

Cited by 21 publications

(19 citation statements)

References 17 publications

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“…In metabolism cage studies (Table 5), water intake was also noted to be significantly increased on day 5 of hormone administration, which is consistent with a previous report demonstrating that endogenous RLX increased water intake in rats during the light period in the second half of gestation (35). Because a decline in the plasma osmolality and osmotic threshold for arginine vasopressin release and water appetite are maternal adaptations in pregnancy (13)(14)(15)(16)(17), it is tempting to speculate that RLX contributes to these responses, especially since they roughly correspond with the appearance of the hormone in the circulation of both rats and humans (1,19).…”

Section: Figuresupporting

confidence: 90%

Relaxin is a potent renal vasodilator in conscious rats

Danielson¹,

Sherwood²,

Conrad³

1999

J. Clin. Invest.

238

254

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The hormone relaxin (RLX) has a molecular weight of approximately 5,000-6,000 and is a member of the insulin-growth factor family. In humans and rats, the ovary is the major, if not sole, source of circulating RLX. In pregnant rats, RLX promotes growth and softening of the cervix and vagina, promotes growth of the mammary nipples, and inhibits spontaneous uterine contractility (reviewed in ref. 1).During early pregnancy in humans, rats, and other mammals, vasodilation of nonreproductive organs leads to a marked decline in total peripheral vascular resistance (2). The kidneys contribute to this fall in peripheral resistance; a nadir in renal vascular resistance and a reciprocal peak in renal blood flow and glomerular filtration rate of 40%-80% above nonpregnant levels are reached by the end of the first trimester in women (reviewed in ref.3). Maximal changes, albeit of a lesser magnitude (20%-40% from nonpregnant levels), are observed in the renal circulation of conscious rats by gestational day 12 (3).The "pregnancy hormones" that cause renal vasodilation and hyperfiltration have not been identified. For several reasons, we hypothesized that RLX contributes. First, the plasma concentration of RLX increases rapidly after conception in women (reviewed in ref. 1), corresponding with the marked increase in both glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) during the first trimester (3). The stimulus for secretion of RLX by the corpus luteum is human chorionic gonadotrophin (hCG), which rises in parallel (1). Second, circulating RLX also increases during the luteal phase of the menstrual cycle (1, 4-6), coinciding with a transient 20% increase in GFR and ERPF (7-12). Third, the gestational rise in RLX corresponds with another early physiological adaptation in human pregnancy, namely, osmoregulatory changes (13). Chronic administration of recombinant human RLX 2 (rhRLX) to ovariectomized rats reduced plasma osmolality and the osmotic threshold for arginine vasopressin release to levels comparable to the gravid condition (14). Fourth, the osmoregulatory changes of pregnancy were mimicked by administering hCG to women in the luteal phase of the menstrual cycle and intact female rats, but not to men or ovariectomized rats, suggesting the intermediary role of an ovarian hormone (15-17). Associated with the osmoregulatory changes observed in women after administration of hCG was a 15%-20% rise in GFR, which again was not observed in men administered the hormone (Davison, J.M., personal communication). Fifth, although renal vasodilation and hyperfiltration are observed in gravid rats as early as day 5 of gestation, before detectable increases in ovarian and plasma RLX occur, there is a marked jump in GFR and ERPF between gestational days 8 and 12 (18) Received for publication October 27, 1998, and accepted in revised form January 4, 1999. Relaxin is a potent renal vasodilator in conscious ratsThe kidneys and other nonreproductive organs vasodilate during early gestation; however, the "pregnancy h...

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Section: Figuresupporting

confidence: 90%

Relaxin is a potent renal vasodilator in conscious rats

Danielson¹,

Sherwood²,

Conrad³

1999

J. Clin. Invest.

238

254

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“…infusion of relaxin causes vasopressin secretion and water drinking in the rat, effects that may be mediated through brain angiotensinergic mechanisms (12,13). Evidence that relaxin [together with other hormones such as angiotensin II (Ang II) and vasopressin] plays a physiological role in regulating body fluid homeostasis during pregnancy is that passive immunization with centrally administered antibodies raised against rat relaxin reduces water drinking in pregnant rats (14), and that chronic i.v. infusion of relaxin in ovariectomized rats results in hyponatremia, mimicking the hyponatremia that occurs in pregnant animals and humans (15).…”

mentioning

confidence: 99%

Circulating relaxin acts on subfornical organ neurons to stimulate water drinking in the rat

Sunn

Egli

Burazin

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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Relaxin, a peptide hormone secreted by the corpus luteum during pregnancy, exerts actions on reproductive tissues such as the pubic symphysis, uterus, and cervix. It may also influence body fluid balance by actions on the brain to stimulate thirst and vasopressin secretion. We mapped the sites in the brain that are activated by i.v. infusion of a dipsogenic dose of relaxin (25 g͞h) by immunohistochemically detecting Fos expression. Relaxin administration resulted in increased Fos expression in the subfornical organ (SFO), organum vasculosum of the lamina terminalis (OVLT), median preoptic nucleus, and magnocellular neurons in the supraoptic and paraventricular nuclei. Ablation of the SFO abolished relaxininduced water drinking, but did not prevent increased Fos expression in the OVLT, supraoptic or paraventricular nuclei. Although ablation of the OVLT did not inhibit relaxin-induced drinking, it did cause a large reduction in Fos expression in the supraoptic nucleus and posterior magnocellular subdivision of the paraventricular nucleus. In vitro single-unit recording of electrical activity of neurons in isolated slices of the SFO showed that relaxin (10 ؊7 M) added to the perfusion medium caused marked and prolonged increase in neuronal activity. Most of these neurons also responded to 10 ؊7 M angiotensin II. The data indicate that bloodborne relaxin can directly stimulate neurons in the SFO to initiate water drinking. It is likely that circulating relaxin also stimulates neurons in the OVLT that influence vasopressin secretion. These two circumventricular organs that lack a blood-brain barrier may have regulatory influences on fluid balance during pregnancy in rats.R elaxin is a peptide hormone secreted by the corpus luteum of the ovary during pregnancy. Relaxin acts on reproductive tissues such as the pubic symphysis, uterus, and cervix (1, 2), but it may also influence the brain (3). Evidence of this influence is presented in reports that the intracerebroventricular (i.c.v.) (1) injection of relaxin results in stimulation of oxytocin and vasopressin secretion, water drinking, and a pressor response (3-8). i.c.v. administration of relaxin also stimulates increased expression of c-fos in groups of neurons in the supraoptic nucleus (SON) and hypothalamic paraventricular nucleus (PVN), as well as in the subfornical organ (SFO), median preoptic nucleus (MnPO), and organum vasculosum of the lamina terminalis (OVLT) (9). Circulating relaxin probably has endocrine actions on the brain, because high-affinity-binding sites for relaxin are present in the SFO and OVLT of the rat (10), two brain regions that are accessible to circulating relaxin because they lack a blood-brain barrier (11). Also, i.v. infusion of relaxin causes vasopressin secretion and water drinking in the rat, effects that may be mediated through brain angiotensinergic mechanisms (12,13). Evidence that relaxin [together with other hormones such as angiotensin II (Ang II) and vasopressin] plays a physiological role in regulating body fluid homeostasis d...

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“…A nondipsogenic dose of angiotensin II was shown to significantly potentiate drinking in response to intravenously infused relaxin [92], suggesting that circulating angiotensin II and relaxin may act synergistically to stimulate water intake in the pregnant animal. Evidence in favor of a role for relaxin in thirst during pregnancy comes from experiments in which administration of relaxin-neutralizing antibodies reduced the fluid intake of pregnant rats [96].…”

Section: Relaxin and Water Drinkingmentioning

confidence: 99%

Cerebral Regulation of Thirst

Mathai

2001

Thermotherapy for Neoplasia, Inflammation, and Pain

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Summary. Thirst, the subjective sensation that motivates humans to drink water, is a basic emotion essential for body fluid homeostasis and survival. In addition to habitual, cultural, and psychogenic drives causing drinking, thirst may arise as a homeostatic response to depletions of the various bodily compartments. Changes in the osmotic pressure of body fluids or alterations in circulating hormones or body temperature signal the brain to induce thirst. Several sensors that play important roles in the generation of homeostatic thirst include cerebral osmoreceptors, sodium sensors, thermosensors, and intrathoracic baroreceptors. Circulating hormones such as angiotensin II, relaxin, and atrial natriuretic peptide (ANP) may also signal the brain to induce thirst. Angiotensin II is not only involved as a circulating hormonal thirst factor but may also playa role as a neurotransmitter in the central neural pathways subs erving drinking behavior. A region of the brain, the lamina terminalis, is crucial in several aspects of homeostatic thirst. The subfornical organ and organum vasculosum of the lamina terminalis (OVLT) are part of the lamina terminalis and lack a blood-brain barrier. These sites contain osmoreceptors and also are sites where blood-borne angiotensin II, relaxin, and ANP act on their specific receptors to influence drinking behavior. The efferent neural pathways from the lamina terminalis that mediate thirst are still obscure. Recent data from human brain imaging suggest a cortical region, the cingulate gyrus, may particpate in the genesis of thirst.

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Monoclonal antibodies specific for rat relaxin. VIII. Passive immunization with monoclonal antibodies throughout the second half of pregnancy reduces water consumption in rats.

Cited by 21 publications

References 17 publications

Relaxin is a potent renal vasodilator in conscious rats

Relaxin is a potent renal vasodilator in conscious rats

Circulating relaxin acts on subfornical organ neurons to stimulate water drinking in the rat

Cerebral Regulation of Thirst

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