Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Microvilli from human placental syncytiotrophoblast are rich in angiotensin I converting enzyme (ACE), aminopeptidase A, a carboxypeptidase N-like enzyme, and a neutral endopeptidase (NEP). The specific activities of these enzymes were enhanced in microvillus-enriched fractions obtained by differential centrifugation: Purified microvilli were isolated in a discontinuous sucrose gradient. The placental microvilli hydrolyzed angiotensin II, vasopressin and oxytocin as shown by high pressure liquid chromatography. The inhibitors, bestatin, phosphoramidon, and o-phenanthroline, established the specificity of the enzymes. Aminopeptidase A (angiotensinase A) cleaved angiotensin II to angiotensin III and Asp1. NEP from placenta and from human kidney hydrolyzed oxytocin at the Pro7-Leu8 bond to yield oxytocin 1-7 and leucyl-glycine amide, but did not hydrolyze vasopressin. Vasopressin was cleaved by aminopeptidases in the placental membranes. On electroblotting placental NEP appeared as a double band with a molecular weight slightly higher than the 90,000 of the purified kidney enzyme. Neuraminidase treatment reduced the molecular weight of the placental enzyme to approximately 90,000, indicating that it contains a large amount of sialic acid. The microvilli of human placenta are thus rich in enzymes that may regulate passage of peptides at the maternal-fetal interface.
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PMID:Enzymes in placental microvilli: angiotensin I converting enzyme, angiotensinase A, carboxypeptidase, and neutral endopeptidase ("enkephalinase"). 609 76

Both fetal and maternal blood pressure is regulated mainly by the humoral factor, vasoactive peptides such as angiotensin II and vasopressin, but not by autoregulation and the autonomic nervous system. It is known that the normal musculoelastic tissue in the vessel wall of the coiled artery, which supplies blood to the uteroplacental blood pool, is replaced by fibrinous tissue with advancing gestation. Therefore uteroplacental circulation is similar to arterio-venous shunt; it is possibly important for the homeostasis of maternal blood pressure. It is known that hypoxemia results in both the redistribution of feto-placental blood flow, the increase of blood flow in the placenta, and the increase of fetal vasoactive peptides. Since placental proteases (vasopressinase and angiotensinase) degrade vasoactive peptides, placental proteases protect the placental vessels from the vasoconstriction by vasoactive peptides and might contribute to the redistribution of feto-placental blood flow. Therefore placental proteases effect on fetal blood pressure via regulation of fetal vasoactive peptides, which regulate placental blood flow. Although human and animal pregnancy is normally associated with a refractory response to the pressor effect of exogenously infused angiotensin II, patients with pre-eclampsia as well as nonpregnant women are sensitive to angiotensin II; thin phenomenon has been studied as one of the causes of pre-eclampsia. Since the administration of placental angiotensinase was effective in lowering blood pressure in rats with hypertension induced by the infusion of angiotensin II, placental proteases are possibly involved in the refractory response to exogenously infused angiotensin II.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Possible role of placental proteases via degradation of vasoactive peptides in the maternal and fetal blood pressure]. 808 9

Although many protease exist in human placenta, their physiologic roles are still unknown. Our study showed that placenta proteases metabolize vasoactive peptides possibly derived from the fetus. Because vasopressin and angiotensin are known to play an important role in normal and aberrant (preeclampsia) fetal-placental circulation, the clearance of these peptides in the placenta is important in controlling fetal blood pressure. Vasopressin and angiotensin act as a fetal-placental vasoconstrictor; therefore, placental proteases in human placenta are likely to work as a clearance factor for these peptides. Although human and animal pregnancy is normally associated with a refractory response to the pressor effect of exogenously infused angiotensin II, patients with preeclampsia, as well as nonpregnant women, are sensitive to the pressor effect of angiotensin II. Our study suggested that the decreased pressor responsiveness to angiotensin II in pregnancy is caused by increased inactivation of angiotensin II by angiotensinase in pregnant serum and the placenta. Although vasopressinase and angiotensinase activities increase with advancing gestation in normal pregnant sera, the activities of both enzymes in severe preeclampsia sera were clearly lower than those in normal pregnancy. Therefore, it is reasonable to speculate that the increased sensitivity to angiotensin II of preeclampsia is attributable to the decreased degradation of angiotensin II by placental angiotensinase. The negative correlations between the systolic to diastolic ratio obtained from pulsed Doppler measurement techniques and the activities of both enzymes in preeclampsia sera suggested that the systolic to diastolic ration, which reflected constriction of placental vessels, is influenced by the concentration of vasoactive peptides in the fetal-placental circulation due to changes in the activities of placental proteases. Placental proteases play important roles in controlling fetal and maternal blood pressure through regulation of the concentration of vasoactive peptides in the interface (placenta) between fetus and mother.
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PMID:Effects of placental proteases on maternal and fetal blood pressure in normal pregnancy and preeclampsia. 878 84

Overactivity of the brain renin-angiotensin system has been implicated in the development and maintenance of hypertension. We reported previously that angiotensin II is converted to angiotensin III by aminopeptidase A in the mouse brain. We then used specific and selective aminopeptidase A inhibitors to show that angiotensin III is one of the main effector peptides of the brain renin-angiotensin system, exerting tonic stimulatory control over blood pressure in hypertensive rats. Aminopeptidase A, the enzyme generating brain angiotensin III, thus represents a potential candidate central nervous system target for the treatment of hypertension. Given this possible clinical use of aminopeptidase A inhibitors, it was, therefore, important to investigate their pharmacological activity after oral administration. We investigated RB150, a dimer of the selective aminopeptidase A inhibitor, EC33, generated by creating a disulfide bond. This chemical modification allows prodrug to cross the blood-brain barrier when administered by systemic route. Oral administration of RB150 in conscious DOCA-salt rats inhibited brain aminopeptidase A activity, resulting in values similar to those obtained with the brains of normotensive rats, demonstrating the central bioavailability of RB150. Oral RB150 treatment resulted in a marked dose-dependent reduction in blood pressure in DOCA-salt but not in normotensive rats, with an ED(50) in the 1-mg/kg range, achieved in <2 hours and lasting for several hours. This treatment also significantly decreased plasma arginine-vasopressin levels and increased diuresis, which may participate to the blood pressure decrease by reducing the size of fluid compartment. Thus, RB150 may be the prototype of a new class of centrally active antihypertensive agents.
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PMID:Orally active aminopeptidase A inhibitors reduce blood pressure: a new strategy for treating hypertension. 1836 27