Tsunekazu Matsumoto

Growth-Dependent Induction of Angiotensin II Type 2 Receptor in Rat Mesangial Cells

Angiotensin II acts on at least two receptor subtypes, AT1 and AT2. Although the physiological role of the AT2 receptor is still poorly defined, it may be implicated in inhibition of cell growth, vasorelaxation, and apoptosis. In the present study, to investigate the role of the AT2 receptor in the kidney and its implication in hypertensive states, we examined its expression using cultured mesangial cells (MC) from normotensive Wistar-Kyoto rats (WKY) and from stroke-prone spontaneously hypertensive rats (SHRSP). Receptor binding assays were performed using a nonselective ligand, [Sar1,Ile8]angiotensin II, or AT2-selective CGP42112A. Binding assays revealed that MC from WKY exhibited both AT1 and AT2 receptors, the ratio of which was confluence-dependent. In contrast, MC from SHRSP, whose proliferation activity was much higher than those from WKY, showed only the AT1 subtype. In receptor binding and Northern blot analyses, expression of the AT2 receptor of WKY-MC was low in the growing state but significantly induced upon confluence to become abundant in the post-confluent state, whereas that of SHRSP-MC was undetectable in either state. Gene expressions of AT1A and AT1B receptors were not significantly altered in either strain during the time in culture. These results indicate that the mesangial AT2-receptor expression is growth-dependent and suggest a role in the inhibition of MC growth in WKY. Much lower expression of the AT2 receptor in MC from SHRSP may suggest involvement in their higher proliferation activity and possibly in consequent renal disorders.

Leptin as a novel placenta-derived hormone in humans

Summary These studies provide the first evidence for leptin as a novel placenta-derived hormone in humans, and suggests the physiologic and pathophysiologic significance of leptin in normal pregnancy and in pregnancies complicated with preeclampsia or gestational trophoblastic diseases. To elucidate the role of leptin in human pregnancy, further investigations on the following points are required. o 1. Mechanism of resistance to high plasma leptin levels during pregnancy has not been elucidated. Studies on down-regulation of leptin receptor and changes in the plasma concentrations of leptin binding protein, which is identical to soluble leptin receptor, Ob-Re, may provide an answer to this question. 2. Possible candidates of the biological significance of placenta-derived leptin in pregnancy may be; a) effects on maternal glucose and lipid metabolism, b) regulation of placental function, and c) effects on fetal growth and development. 3. Identification of distribution of leptin receptors in intra-uterine tissues is crucial to understand the role of placenta-derived leptin during pregnancy.

Role of the guanylate cyclase system in the regulation of ovine uterine arterial blood flow during pregnancy: A review

Summary We have previoulsy demonstrated a 38-fold increase in cGMP secretion from the gravid ovine uterus, and a 2-fold increase in plasma and urinary cGMP levels. cGMP causes potent vasodilation and there are two major guanylate cyclases, cGMP production pathways, NO/sGC and natriuretic peptide/pGC-A/B pathways, in ovine UA. Pregnancy up-regulates both pathways, concomitantly with down-regulation of UA CR, contributing to the dramatic increase of cGMP production in ovine UA. This suggests a possible role for the local vascular guanylate system in the regulation of increased uterine blood flow during pregnancy.