Osmoregulation, the secretion of arginine vasopressin and its metabolism during pregnancy

Lindheimer MD, Davison JM. Osmoregulation, the secretion of arginine vasopressin and its metabolism during pregnancy. Eur J Endocrinol 1995;132:133–43. ISSN 0804–4643 This review stresses changes in osmoregulation as well as the secretion and metabolism of aŕginine vasopressin during pregnancy, focusing on human gestation. Pregnant women experience a decrease in body tonicity, plasma osmolality decreasing immediately after conception to a nadir ~ 10 mosmol/kg below non-pregnant levels early in pregnancy, after which a new steady state is maintained until term. Data from both human and rodent gestation have led to a formation of how these changes occur. The osmotic thresholds for thirst and antidiuretic hormone release decrease in parallel. Lowering the threshold to drink stimulates increased water intake and dilution of body fluids. Because arginine vasopressin (AVP) release is not suppressed at the usual level of body tonicity, the hormone continues to circulate and the ingested water is retained. Plasma osmolality declines until it is below the osmotic thirst threshold, and a new steady state with little change in water turnover is established. Pregnancy is characterized by increments in intravascular volume, but volume-sensing AVP release mechanisms appear to adjust as gestation progresses so that each new volume status is "sensed" as normal. The metabolic clearance of AVP increases fourfold, the rise paralleling that of circulating cystine aminopeptidase (vasopressinase), and enzyme produced by the placenta. Furthermore, the disposal rate of 1-deamino-8-d-AVP, and AVP analogue resistant to inactivation by vasopressinase, is unaltered in pregnancy. Thus, the increase in AVP's metabolism and the high circulating aminopeptidase levels have been implicated in certain forms of transient diabetes insipidus that occur in late pregnancy. Finally, mechanisms responsible for the altered osmoregulation in pregnancy are obscure, but chorionic gonadotropin and relaxin may be implicated in the changes. M Lindheimer, Section of Nephrology, MC 5100, University of Chicago Hospitals, 5841 S Maryland Ave, Chicago, IL, USA

Loss of osmotic thirst in multiple system atrophy: association with sinoaortic baroreceptor deafferentation

We evaluated plasma osmolality (pOsm), thirst, and vasopressin response to hypertonic saline infusion in 14 patients with multiple system atrophy (MSA). This disease is characterized by the degeneration of noradrenergic neurons in the central nervous system and severe orthostatic hypotension. Seven patients were also characterized by the lack of vasopressin response to hypotension (group B) and seven by a preserved response (group A). In group A pOsm rose from 290 +/- 2 to 312 +/- 6 mosmol/kgH2O, vasopressin from 0.9 +/- 0.3 to 5.7 +/- 0.5 pmol/l, and thirst from 1.1 +/- 0.1 to 8.7 +/- 1.1 cm on the visual analog scale. After saline, patients drank 1,215 +/- 150 ml of water (no different from healthy controls). In group B patients' pOsm rose from 296 +/- 3 to 325 +/- 6 mosmol/kgH2O and vasopressin from 1.2 +/- 0.1 to 19.6 +/- 0.4 pmol/l (P < 0.01 vs. group A and controls). Group B patients had no thirst during saline and drank little after the challenge (175 +/- 50 ml; P < 0.01 vs. group A and control). Forced drinking decreased vasopressin in patients before changes in pOsm, showing that inhibitory afferents from oropharyngeal mucosa were intact. In MSA patients with altered afferent control of vasopressin there is a dissociation between the osmotic control of thirst and the osmotic control of vasopressin.

Osmoregulation of thirst and vasopressin release in pregnancy

Osmoregulation is altered in human gestation, body tonicity declining to a nadir early in pregnancy after which a new steady-state plasma osmolality is maintained until term. Development of precise, sensitive, and specific radioimmunoassays for arginine vasopressin (AVP), which permit clearer definitions of functional properties of the osmoregulatory system, have led to a formulation of how these changes occur (both in women as well as in a gravid rat model). The osmotic thresholds for thirst and antidiuretic hormone release each decrease approximately 10 mosmol/kg during the initial weeks of human gestation. Lowering the threshold to drink stimulates increased water intake and dilution of body fluids. Because AVP release is not suppressed at the usual levels of tonicity, it still circulates and water is retained. Osmolality declines until it decreases below the osmotic thirst threshold (situated several mosmol/kg above that for hormone secretion), and a new steady state, with little change in water turnover, is established. The metabolic clearance rate of AVP is also altered, increasing three- to fourfold between gestational week 10 and midtrimester, paralleling the appearance and rapid rise in circulating cystine-aminopeptidase (vasopressinase), an observation that may explain several disorders of water handling that complicate human pregnancy. Finally, mechanisms responsible for the altered osmoregulation are obscure but chorionic gonadotropin may be involved in the changes during human gestation.