We performed this study to examine the presence of a kallikrein-kinin system in rat fetal and maternal tissues. Uteri and placenta from Wistar pregnant and nonpregnant rats were perfused to eliminate blood, and fetal membranes were washed several times with saline. Amniotic fluids were obtained without blood contamination by amniocentesis from eight rats. The different samples were homogenized and centrifuged (2000g during 20 minutes), and the supernatant was incubated with dog kininogen and 0.1 mol/L Tris-HCl buffer (pH 8.5) in the presence of peptidase inhibitors. Kinins released were measured by radioimmunoassay. Kininogenase activity was found in rat uteri, placental vessels, amniotic fluids, and fetal membranes. The enzymes were present in active but mostly in inactive forms. The kallikrein-like enzymes found in the different preparations and rat urinary kallikrein used as control had similar molecular weights, immunologic characteristics, and inhibition profiles with protease inhibitors. We conclude that kallikrein-like enzymes are present in rat organs of reproduction. These data suggest that kinins released locally may act as paracrine hormones in the regulation of blood pressure during pregnancy. changes that enable the gravida to accommodate the growing products of conception. These changes -quite profound in the cardiovascular system, kidney, and uterus-have been characterized extensively but never understood completely. Despite increases in plasma volume and cardiac output, blood pressure actually declines.1 This reduction occurs because peripheral vascular resistance in pregnancy decreases significantly from normal nonpregnant levels. 2The renin-angiotensin-aldosterone system is activated markedly during pregnancy.3 Decreased blood pressure in the face of elevated plasma levels of angiotensin suggests that pregnant women are resistant to the pressor effect of angiotensin. Precisely why pregnancy reduces peripheral vascular resistance is unknown. Recently, it has been proposed that the reduced peripheral vascular resistance is due to an increased production of vasodilator substances. 4 Kinins are potent vasodilator peptides released from kininogen by kininogenases. There is now clear evidence that part of the hemodynamic effect of kinins are mediated by prostaglandins and endothelium-derived relaxing factors. Kallikrein has been implicated in the regulation of uteroplacental blood flow 57 ; however, whether or not kallikrein can be found within these tissues is not known. Although kinin-forming activity has been reported in human organs of reproduction, 8 further characterization is needed because proteases other than kallikrein can also release kinins. In this study we examined the presence and biochemical characteristics of kallikrein-like enzymes in the uteroplacental-fetal complex. MethodsAdult female Wistar rats between 14 and 15 days' gestation (term rat pregnancy, 22 days) weighing 200 to 250 g were anesthetized with sodium pentobarbital (50 mg/kg IP). The animals were treated in acco...

Gastrin is secreted mainly by G‐cells in the stomach and released into the circulation. It is taken up by renal tubules where it acts on cholecystokinin B receptors (CCKBR) to decrease sodium reabsorption. However, it is unknown whether or not gastrin can also be produced by the kidney and participate in the control of sodium homeostasis and blood pressure.We used real‐time RT‐PCR to determine the expression of gastrin mRNA in different areas of the mouse kidney and found the gastrin transcript in both medulla and papilla, indicating that gastrin may be synthesized in the kidney. Gastrin immunoreactivity was detected in the thin descending limb of Henle's loop (TDLHL), which was confirmed by colocalization with aquaporin 1, a marker of TDLHL. Expression of gastrin protein was also found in mouse kidney homogenates. In contrast, real‐time RT‐PCR, western blotting, and immunostaining revealed no expression of gastrin in the kidney of gastrin knock‐out (Gast −/−) mice. In addition, Gast−/− mice have higher blood pressure and lower sodium excretion than Gast+/+ mice.These results show for the first time that gastrin is expressed in the TDLHL of the mouse kidney. Furthermore, renal gastrin might contribute to increase sodium excretion and maintain normal blood pressure.