Vasopressin (VP) is a non-peptide hormone synthesized in the paraventricular nucleus (PVN) and supraoptic nucleus (SON), functioning as a neuroendocrine and autonomic regulator of the cardiovascular system, implicated in the pathogenesis of hypertension. There are three types of VP receptors: V1a, V1b, and V2. The V1a receptor is found in vascular smooth muscle cells, the V1b receptor in the anterior pituitary gland, and the V2 receptor in the renal collecting ducts, where it mediates antidiuretic effects [1]. The well-known antidiuretic action of VP is attributed to the V2 receptor, which, upon stimulation by VP, translocate AQP2 from intracellular compartments to the cell surface of the collecting ducts, facilitating water reabsorption from the primary urine and concentrating the urine. In heart failure, AQP2 expression in renal tubules is observed and has been reported to be suppressed by the administration of V2 receptor antagonists [2]. The V2 receptor antagonist tolvaptan is currently used for treating heart failure, cirrhosis, and hyponatremia. In other areas, VP is used in the treatment of patients with septic shock during sepsis. For pregnancy, VP has also been extensively studied in pregnancy with fluid retention, and a mouse model of vasopressin-induced preeclampsia has recently been reported [3]. Additionally, placental ischemia during pregnancy has been reported to increase salt sensitivity and contribute to hypertension in the postpartum period through the production and secretion of VP, highlighting its importance VP in salt-sensitive hypertension following preeclampsia [4]. However, the physiological changes in VP during pregnancy in chronic hypertension remain unknown (Fig. 1).

Fig. 1
figure 1

The change of vasopressin comparing hypertensive pregnancy and normal pregnancy

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Jovanović et al. studied the gene expression of VP and its V1aR and V1bR receptors within the PVN and SON in spontaneously hypertensive rats (SHRs) and Wistar rats (WRs), comparing it to autonomic cardiovascular adaptations during pregnancy [5]. The results demonstrated that pregnancy decreased the expression of VP in SON in SHR, whereas it increased VP expression in WR. This was accompanied by elevated expression of V1bR and reduced plasma VP concentrations in SHR in late pregnancy compared to WR in late pregnancy. Furthermore, blood pressure in SHR decreased in late pregnancy, which is marked by increased sympathetic stimulation of the heart and signs of mobilization of vagal mechanisms to counter this stimulation, revealing a vulnerable cardiovascular system. These phenomena are intriguing.

Cardiac output (CO), plasma renal plasma flow (RPF), and glomerular filtration rate (GFR) increase by 6 weeks of gestation, accompanied by a decrease in systemic vascular resistance in humans [6]. Furthermore, not only GFR, RPF but also CO and vascular resistance in pregnant rats treated with nitric oxide (NO) inhibitor L-NAME from day 7 to 14 of gestation, which is midterm, were reversed to the levels of non-pregnant rats [7]. Therefore, it is understood that NO-induced vasodilation occurs, followed by fluid overload. However, the mechanisms underlying these physiologic changes are not fully elucidated. In pregnant rats, plasma arginine vasopressin levels are detectable despite significantly decreased plasma osmolality [8]. Additionally, both mRNA and protein expressions of AQP2 have been shown to increase during pregnancy, and these changes are associated with non-osmotic stimulus of vasopressin [9]. Similarly, urinary AQP2 has been shown to increase in human pregnancy [10]. This phenomenon is understood to augment total blood volume for placental blood supply during pregnancy by resetting the osmotic threshold for vasopressin secretion to a lower osmotic pressure to maintain pregnancy [11]. In other words, this change is considered an adaptation to pregnancy.

On the other hand, plasma VP levels in SHRs were significantly lower than in WR, as was the expression of VP in SON, in late pregnancy. Furthermore, SHRs exhibited lower blood pressure in late pregnancy [5]. Although fluid volume was not assessed in this study, it is reasonable to assume that the decrease in blood pressure is associated with vascular resistance and represents an adaptation to hypertension. These findings are novel. However, it may be necessary to note that the evaluation of VP concentration is related to osmotic pressure and fluid volume.

In future studies, it may be important to examine whether changes in plasma VP and cardiovascular vulnerability in late pregnancy can be treated by interventions such as salt restriction and anti-hypertensive drugs in pregnant hypertensive rats. This situation is analogous to the management of pregnant women with chronic hypertension in real-world. Understanding the role of VP is crucial, as recent years have shown that aggressive therapeutic intervention for pregnant woman with mild chronic hypertension is associated with favorable maternal and fetal outcomes [12].