Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recently we demonstrated that the vascular response to angiotensin II (A-II) was attenuated in an endothelium-dependent manner by using the isolated ring specimen iliac arteries of pregnant rabbits. In this paper we investigated the possibility that three vasoactive substances, thromboxane A2(TXA2), prostacyclin (PGI2), and endothelium-derived nitric oxide (EDNO), might be involved in this refractoriness to A-II during pregnancy, by measuring the changes in the vascular response to A-II (pA2, intrinsic activity) of the isolated arterial rings of rabbits before and after the addition of an inhibitor specific for each of these three substances. Sodium ozagrel, TXA2 synthetase inhibitor, decreased the vascular response to A-II more in the blood vessels of pregnant rabbits, regardless of whether the endothelium was intact or denuded, than in the blood vessels of non pregnant rabbits. Tranylcypromine, a PGI2 synthetase inhibitor, significantly increased contractility in the blood vessels with intact endothelium of pregnant rabbits (i.a. = 1.39 +/- 0.099, n = 11, mean +/- SEM), compared to that in the blood vessels with intact endothelium of non pregnant rabbits (i.a. = 1.08 +/- 0.090, n = 7). Methylene blue, a guanylate cyclase inhibitor which blocks the effect of EDNO, amplified the vascular response in blood vessels with intact endothelium of both groups, and more intensely in the blood vessels of pregnant rabbits.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effect of endothelium-derived nitric oxide and prostaglandins on the endothelium-dependent vascular refractoriness to angiotensin II in pregnant rabbits]. 145 44

Enzymes involved in prostaglandin I2 (PGI2) and thromboxane A2 (TXA2) synthesis were studied in maternal and fetal platelets and venous endothelium from normotensive pregnant controls (n = 70), women with mild preeclampsia (MP, n = 45), and severe preeclampsia (SP, n = 34). Activities of phospholipase A2 (PHA2), cyclooxygenase (PGHS), and PGI2 synthetase (PGIS) or TXA2 synthetase (TXAS) were determined in platelets and in endothelial cells. The PGHS enzyme was studied further by immunoblot methodology. In maternal platelets: Vmax (per 10(-10) mol/mg protein) and Michaelis-Menten constant (Km) (10(-7) mol, mean +/- SEM) of PHA2 were 3.0 +/- 0.8, 3.0 +/- 0.7, and 31.7 +/- 10.9* maximum velocity (Vmax) and 1.8 +/- 0.3, 2.0 +/- 0.8, and 0.8 +/- 0.2 (Km) in normal control (NC), mild preeclampsia (MP), and severe preeclampsia (SP), respectively (*P less than 0.05 against NC). The apparent overall PGHS plus TXAS activity was 10.2 +/- 1.8, 23.8 +/- 7.1, and 68.8 +/- 18.8* (Vmax) and 3.2 +/- 1.3, 5.4 +/- 1.4, and 6.9 +/- 1.2* (Km, *P less than 0.05 against NC). TXA synthesis in fetal platelets demonstrated PHA2 activity of 6.4 +/- 1.4, 12.0 +/- 1.3, and 17.2 +/- 3.2* (Vmax) and 3.5 +/- 0.9, 2.2 +/- 1.5, and 0.7 +/- 0.3* (Km, *P less than 0.05 against NC), respectively, whereas an apparent overall PGHS plus TXAS activity was 18.5 +/- 2.8, 87.5 +/- 12.5*, and 3.6 +/- 0.1* (Vmax) and 4.8 +/- 1.0, 8.8 +/- 1.2, and 0.8 +/- 0.3* (Km, *P less than 0.05 against NC).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of prostaglandins in pregnancy-induced hypertension. 189 31

The role of bradykinin in the ovulatory process was investigated using an in vitro-perfused rat ovary model. Stimulation with LH (0.1 micrograms/ml) resulted in 2.6 +/- 0.5 (mean +/- SEM) ovulations per ovary, whereas no ovulations occurred in the nonstimulated control group. Bradykinin (5 microM) added to the perfusion system hourly for 10 h induced 2 of 5 ovaries to ovulate, with 2 and 3 ovulations, respectively. When bradykinin (5 microM) was given as a single dose at 5 or 10 h after LH, the ovulation rate was significantly increased to 11.0 +/- 2.8 and 8.6 +/- 2.0 ovulations per ovary, respectively. A competitive bradykinin antagonist, phenylalanine bradykinin, inhibited the bradykinin-induced increase in LH-stimulated ovulations. The addition of LH, but not of bradykinin, increased the levels of prostaglandin endoperoxide synthase in granulosa cells, but the levels of the enzyme in the residual ovarian tissue were negligible. In contrast, prostacyclin synthase was predominantly located in the residual ovarian tissue. This enzyme was not affected by LH or bradykinin. LH increased the tissue levels of prostaglandins, predominantly prostaglandin E2 (PGE2), at 7 h, whereas the stimulatory effect of bradykinin was smaller, with a preferential increase in prostacyclin (prostaglandin I2) levels. This study indicates a modulatory role of bradykinin, possibly involving prostacyclin late in the ovulatory process, in the rat.
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PMID:Stimulatory effects of bradykinin on the ovulatory process in the in vitro-perfused rat ovary. 200 29

There is evidence that cyclooxygenase products of arachidonic acid participate in the control of renin release. In this study we tested the hypothesis that prostaglandin (PG) I2 and/or its metabolite(s), which are synthesized in the afferent arteriole (AF), stimulate renin release by acting directly on the AF while PGE2 stimulates renin release indirectly via the macula densa. AF alone and AF with macula densa attached (AF-MD) were microdissected from rabbit kidneys and incubated in vitro. The renin release rate from a single AF (or an AF-MD) was calculated and expressed as ng AI.hr-1. AF-1/hr (where AI is angiotensin I). When arachidonic acid (0.12 mM) or PGI2 (10 microM) was added to AF, renin release increased significantly (P less than 0.0001) from 1.04 +/- 0.21 to 3.12 +/- 0.86 (x +/- SEM, N = 7), and from 0.45 +/- 0.14 to 1.48 +/- 0.53 (N = 9), respectively. During the recovery period, renin release increased even further, reaching 9.53 +/- 1.76 and 4.50 +/- 1.24, respectively. A PGI2 synthetase inhibitor, 9, 11-azoprosta-5,13-dienoic acid blocked the effect of arachidonic acid. To examine whether the increases in renin release during the recovery period were due to metabolite(s) of PGI2, we tested the effect of both 6-keto-PGE1 (an active metabolite of PGI2) and carba-PGI2 (a synthetic analog that is metabolized differently from PGI2). Six-keto-PGE1 and carba-PGI2 increased renin release only during the experimental period with no further increase during the recovery period.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of prostanoids on renin release from rabbit afferent arterioles with and without macula densa. 250 84

To elucidate the cause of low prostacyclin (PGI2) production in severe preeclampsia (PE), we studied the activities of phospholipase A2, cyclooxygenase, and PGI2 synthase in umbilical venous endothelial cells obtained from healthy pregnant women and from patients with mild or severe PE. Umbilical venous endothelial cells homogenized in a buffer solution were analysed by calculating the apparent Vmax (mean +/- SEM: p mol/min mg protein) and Km (mean +/- SEM: microM) values for phospholipase A2 activity by the release of arachidonic acid from phosphatidylcholine, for the activity of a complex of cyclooxygenase and PGI2 synthase by the conversion of arachidonic acid to PGI2, and the activity of PGI2 synthase by conversion of PGH2 to PGI2. The phospholipase A2 activity of normal-pregnancy cells (Vmax: 17.0 +/- 2.7 Km: 0.26 +/- 0.04) (n = 10) significantly exceeded that of cells from women with either mild PE (5.8 +/- 0.5, 0.12 +/- 0.02) (n = 4) or severe PE (6.3 +/- 2.0, 0.08 +/- 0.03) (n = 5). The apparent combined activity of cyclooxygenase and PGI2 synthase in mild PE (552 +/- 142, 0.29 +/- 0.07) (n = 8) significantly exceeded that of a normal pregnancy (176 +/- 42, 0.76 +/- 0.25) (n = 7), whereas that in severe PE (326 +/- 36, 3.26 +/- 0.78) (n = 3) was significantly lower than that of a normal pregnancy. PGI2 synthase activity in mild PE (305 +/- 50, 0.12 +/- 0.07) (n = 4) exceeded that of a normal pregnancy (220 +/- 45, 0.13 +/- 0.06) (n = 5), whereas that in severe PE (55 +/- 12, 0.16 +/- 0.04) (n = 3) was lower than that of a normal pregnancy. The phospholipase A2 activity in cells of normal pregnant women exceeded that of cells of women with mild or severe PE. The combined activity of cyclooxygenase and PGI2 synthase in a normal pregnancy was lower than in mild PE, but higher than in severe PE. Similar results were found for PGI2 synthase activity; in normal pregnancy the activity was less than in mild PE, but higher than in severe PE.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Activities of phospholipase A2, cyclooxygenase, and PGI2 synthase of umbilical venous endothelial cells in preeclamptic women. 783 76

Since serotonin (5-HT) is implicated in exacerbating acute coronary syndromes, we studied the reactivity of atrial coronary arterioles (70-140 microm) of atherosclerotic patients undergoing cardiac surgery to 5-HT, substance P (Sub P), and sodium nitroprusside by video-microscopy. Before ischemia, 5-HT-induced relaxation was not affected by NS398 (cyclooxygenase inhibitor), H2O2 or U63557A (thromboxane A2 synthase inhibitor), but was reduced by L-NNA. 5-HT elicited a potent contractile response after ischemia that was inhibited by NS398, Indo, and U63557A. While Sub P relaxation was decreased after ischemia, SNP relaxation was unchanged. The mRNA steady-state levels of NOS-3, NOS-2, prostacyclin synthase, and COX- 1 were not altered by ischemia. COX-2 mRNA and protein levels (Westernblotting), however, were increased (mean +/- SEM) 2.4 +/- 0.4 and 3.2 +/- 0.7 fold, respectively, in ischemic atrium corroborating with the immunohistochemistry of atrial tissue. It is concluded that myocardial ischemia enhanced contractile response of coronary arterioles to 5-HT maybe due to the stimulated prostaglandin release (likely thromboxane A2) secondary to induction of COX-2 expression. These findings may have implications regarding the cause of coronary spasm during acute myocardial ischemia.
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PMID:Serotonin-induced human coronary microvascular contraction during acute myocardial ischemia is blocked by COX-2 inhibition. 1121 33