Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:4.6.1.2 (guanylate cyclase)
8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To study the effects of progesterone on placental vascular tone, we used isolated (1-2 mm in diameter) placental arteries and veins from term uncomplicated pregnancies. These vessels, incubated in Krebs buffer (pH 7.4) under 5% O2-5% CO2 (balance N2, PO2 approximately 35 torr) and precontracted with serotonin were exposed to incremental doses of progesterone (0.01-30 mumol/L) in the presence or absence of endothelium, 10 mumol/L indomethacin (inhibits prostaglandin synthesis), 10 mumol/L methylene blue (a soluble guanylate cyclase inhibitor), 100 mumol/L nitro-L-arginine (inhibits L-arginine metabolism), 1 mmol/L isobutylmethylxanthine (a cAMP phosphodiesterase inhibitor), or 30 mumol/L mifepristone (RU 38486, an antiprogestin). Progesterone elicited an acute dose-dependent relaxation in both arteries and veins that was not altered by removal of the endothelium or pretreatment with indomethacin, nitro-L-arginine, or methylene blue, excluding a role for prostaglandins, L-arginine products, or cGMP in mediating this relaxation. However, isobutylmethylxanthine significantly enhanced the relaxation in response to progesterone, suggesting a role for cAMP. RU 38486 inhibited the relaxation by 50-100%, depending on the progesterone dose, consistent with a role for progesterone receptors. These results suggest that progesterone causes a dose-dependent endothelium-independent relaxation of human placental arteries and veins. This relaxation seems to be mediated by a receptor-activated cAMP mechanism and could be physiologically important in maintaining low resistance and adequate blood flow in the placental circulation.
...
PMID:Properties of a progesterone-induced relaxation in human placental arteries and veins. 785 92

In perinatal lungs, veins contribute substantially to total pulmonary vascular resistance. The present study was designed to determine the role of endothelium-derived nitric oxide (EDNO) in modulating the responsiveness of pulmonary veins and arteries in newborn lambs. Fourth-order pulmonary arterial and venous rings of newborn lambs were suspended in organ chambers filled with modified Krebs-Ringer bicarbonate solution (95% O2/5% CO2, 37 degrees C), and their isometric force was measured. Nitro-L-arginine had no effect on the resting tension of pulmonary arteries but caused an endothelium-dependent contraction of pulmonary veins. During contraction to endothelin-1 or U46619, acetylcholine, bradykinin, and calcium ionophore A23187 induced larger endothelium-dependent relaxation in pulmonary veins than in arteries. The endothelium-dependent relaxation of pulmonary vessels was abolished by nitro-L-arginine. In vessels without endothelium, nitric oxide induced significantly greater relaxation in pulmonary veins than in arteries. All vessels relaxed similarly to 8-bromo-cGMP. Radioimmunoassay showed that the basal level of intracellular cGMP of pulmonary veins with endothelium was higher than that of arteries with endothelium. Acetylcholine, bradykinin, and calcium ionophore A23187 induced a significantly larger endothelium-dependent increase in the intracellular content of cGMP in pulmonary veins than in arteries. In vessels without endothelium, nitric oxide induced a larger increase in cGMP content in pulmonary veins than in arteries. The present study suggests that EDNO may play a larger role in modulation of pulmonary venous than arterial reactivity, which may be mainly due to a difference in the activity of soluble guanylate cyclase in vascular smooth muscle.
...
PMID:Endothelium-derived nitric oxide plays a larger role in pulmonary veins than in arteries of newborn lambs. 789 31

To examine the effect of a prior episode of anoxia on subsequent anoxia-mediated vasorelaxation, norepinephrine-precontracted endothelium-intact rat aortic rings were first exposed to anoxia (95% N2-5% CO2 for 5, 15, or 30 min) then to normoxia (95% O2-5% CO2 for 15 min). These rings were exposed again to anoxia for 30 min. First exposure of rings to anoxia for 30 min resulted in 77 +/- 4% decrease in tone (vasorelaxation), whereas second exposure resulted in only 10 +/- 4% relaxation (n = 11, P < 0.001 vs. relaxation during first exposure). First exposure of rings to anoxia for 5 or 15 min also diminished relaxation to 59 +/- 3 and 19 +/- 8%, respectively, on second exposure to anoxia (both P < 0.01 vs. relaxation during 1st anoxia). Attenuation of vasorelaxation by prior episode of anoxia was not affected by treatment of rings with indomethacin (10(-5) M), the Ca2+ channel blocker felodipine (10(-6) M), the superoxide anion scavenger superoxide dismutase (100 micrograms/ml), or adenosine A1 and A2 blockers (each 10(-6) M). To examine the role of intact functional endothelium in attenuation of vasorelaxation during second anoxic exposure, rings were deendothelialized and treated with the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA; 10(-4) M) or the guanylate cyclase inhibitor methylene blue (MB; 2 x 10(-5) M). In all deendothelialized rings, vasorelaxation during second anoxic exposure was similar to that during first anoxic exposure (100 +/- 0 vs. 98 +/- 3%, P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Prior episode of anoxia attenuates vasorelaxation in response to subsequent episode of anoxia. 816 Aug 46

Both atherosclerotic lesions and hypoxia alter the contractile properties of the arterial wall and, in particular, may interfere with the relaxation mechanisms dependent or not on the endothelium. The present study was designed to test the effect of severe hypoxia on the contractile behavior of the atherosclerotic rabbit aorta. Segments of aortas obtained from control, cholesterol-fed, or Watanabe hereditary hyperlipidemic rabbits were mounted in organ chambers for isometric tension recording. A change of the bath PO2 from "normoxic" conditions (95% O2-5% CO2) to "hypoxic" conditions (95% N2-5% CO2) caused relaxation in the precontracted control aortas (by approximately 85%) but a transient contraction (approximately 20% of the maximal contraction obtained with 30 mM KCl) followed by a relaxation in the precontracted atherosclerotic aortas. Both types of responses were observed in aortas contracted with aggregating platelets, 5-hydroxytryptamine (5-HT), norepinephrine, endothelin, and prostaglandin F2 alpha. The hypoxic contractions in atherosclerosis were not dependent on the presence of an intact endothelium. They could not be antagonized by blockers of alpha-adrenoceptors, 5-HT2 receptors, histamine receptors, thromboxane receptors, and muscarinic cholinoreceptors. Inhibitors of cyclooxygenase, lipoxygenase, Na+, K(+)-ATPase, and free radical scavengers or an activator of endothelium-derived relaxing factor did not significantly affect the hypoxic contraction; the absence of effect of some inhibitors of protein synthesis seems to rule out the involvement of endothelin, angiotensin II, and bradykinin. The hypoxic contraction was not influenced by omission of Ca2+ from the medium or by inhibition of Ca2+ influx but was prevented by blockade of intracellular Ca2+. The inhibitor of nitric oxide synthase (nitro-L-arginine, 100 microM) and the guanylyl cyclase inhibitor (methylene blue, 10 microM) both enhanced the initial contractile responses to 5-HT to a similar extent as hypoxia and completely prevented the hypoxic contraction in the atherosclerotic tissues. The cyclic nucleotide analogues 8-bromo-cGMP and dibutyryl cAMP also inhibited the hypoxic contraction in the atherosclerotic aorta. The cGMP levels were markedly decreased and the cAMP levels were moderately decreased in the aortas of the cholesterol-fed rabbits as compared with the control aortas. Hypoxia further decreased cGMP but not the cAMP levels in atherosclerotic aortas with and without endothelium. Our data thus demonstrate the occurrence of an unusual vasoconstrictor response in atherosclerotic arteries; this constrictor response depends on the availability of intracellular Ca2+ and seems to be due to the further inhibition of an already impaired cGMP production.(ABSTRACT TRUNCATED AT 400 WORDS)
...
PMID:Hypoxia causes an abnormal contractile response in the atherosclerotic rabbit aorta. Implication of reduced nitric oxide and cGMP production. 838 23

Experiments were designed to determine the role of the L-arginine pathway in endothelium-dependent relaxations to vasopressin. The effects of L-arginine analogues NG-nitro-L-arginine (L-NNA), NG-nitro-L-arginine methyl ester (L-NAME), and NG-monomethyl-L-arginine (L-NMMA) on basal and vasopressin-induced activity of nitric oxide synthase were studied in isolated canine basilar arteries. Rings with and without endothelium were suspended for isometric tension recording in Krebs-Ringer bicarbonate solution bubbled with 94% O2-6% CO2 (37 degrees C, pH 7.4). Radioimmunoassay was used to determine the level of guanosine 3',5'-cyclic monophosphate (cGMP). All experiments were performed in the presence of indomethacin, a cyclooxygenase inhibitor. L-NAME and L-NMMA caused endothelium-dependent contractions and inhibited basal production of cGMP. In contrast, L-NNA did not affect basal tone or basal production of cGMP. L-Arginine analogues inhibited relaxations to vasopressin but did not affect relaxations to a nitric oxide donor, molsidomine (SIN-1). The effects of L-NNA, L-NAME, and L-NMMA were reversed in the presence of L-arginine. The relaxations to vasopressin were associated with an increase of cGMP levels in the arterial wall. This effect of vasopressin was inhibited in the presence of L-NNA. These studies suggest that the relaxations to vasopressin are mediated by activation of the endothelial L-arginine pathway, leading to increased production of nitric oxide, with subsequent activation of guanylate cyclase in smooth muscle cells. In canine basilar artery, L-NAME and L-NMMA are nonselective inhibitors of both basal and stimulated production of nitric oxide, whereas L-NNA selectively inhibits vasopressin-induced activation of the L-arginine pathway.
...
PMID:Endothelial L-arginine pathway and relaxations to vasopressin in canine basilar artery. 838 55

To evaluate the cellular mechanisms involved in hypoxic relaxation of airway smooth muscle, we investigated the effects of hypoxia on the behavior of third- and fourth-order porcine bronchial rings contracted with either carbachol or KCl. In one series of experiments, hypoxia (95% N2-5% CO2) was imposed and rings were then exposed to increasing concentrations of carbachol or KCl. In separate experiments, rings were first contracted with carbachol (10(-6) M) or KCl (40 mM) and were then exposed to solutions bubbled with decreasing concentrations of O2. The CO2 concentration was maintained constant at 5% in all experiments. The initial magnitude of KCl-induced but not carbachol-induced contractions was profoundly reduced by 95% N2-5% CO2. The sensitivity of the airway to carbachol was unchanged. In rings precontracted with either carbachol or KCl, hypoxia caused similar losses of airway smooth muscle tone in a reversible and concentration-dependent manner. The effects of hypoxia were independent of the presence of an intact epithelium and were not inhibited by the cyclooxygenase inhibitor indomethacin (5 microM), the soluble guanylate cyclase inhibitor methylene blue (50 microM), or the beta-adrenoceptor antagonist propranolol (1 microM). The impairment by hypoxia of the initiation phase of KCl-induced contractions and of the maintenance phase of both KCl- and carbachol-induced contractions, but not the initiation phase of carbachol-induced contractions, suggests that changes in O2 tension modulate airway tone by altering the entry of extracellular calcium into the airway smooth muscle.
...
PMID:Role of Ca2+ entry in the modulation of airway tone by hypoxia. 846 Jul 17

During human pregnancy, ACTH is produced by both the placenta and fetal pituitary. ACTH has been shown to cause vasodilatation in the adrenal cortex in vitro. In this context we have investigated the vasoactive effects of ACTH in the human fetal-placental circulation. Single lobules of term human placentas were bilaterally perfused in vitro with Krebs solution (maternal and fetal, 5 mL/min; 95% O2-5% CO2; 37 C; pH 7.3), and changes in fetal placental arterial perfusion pressure (FAP) were measured. ACTH (40-4000 pmol/L; n = 5) caused a dose-dependent reduction of both KC1 and PGF2alpha-induced increases in FAP in the fetal placental circulation. The reductions were of a similar magnitude in the presence of either constrictor agent. ACTH was 187.4 (95% confidence limits, 162.7-215.9) times more potent than prostacyclin (PGI2; 1.2-1180 nmol/L; n = 6), which is a known vasodilator of the fetal-placental circulation. The threshold concentrations for ACTH and PGI2 were 40 pmol/L and 1.2 nmol/L, respectively. ACTH-induced reductions in PGF2alpha-induced increases in FAP in the fetal placental circulation were not inhibited by the nitric oxide synthase inhibitor, N omega-nitro-L-arginine (100 micromol/L; n = 5), the cyclooxygenase inhibitor indomethacin (3 micromol/L; n = 5), or a guanylate cyclase inhibitor LY83583(1 micromol/L; n = 5). The inhibitory effect of ACTH was attenuated by the antagonist, ACTH-(7-38) (240 pmol/L; n = 4), and a polyclonal ACTH antiserum (1:1000 dilution; n = 4). We have demonstrated that ACTH causes a reduction in fetal placental vascular resistance in the human fetal-placental circulation in vitro. The mechanism by which it exerts these effects has not been defined, but neither nitric oxide nor PG-mediated pathways appear to be involved.
...
PMID:Adrenocorticotropin causes vasodilatation in the human fetal-placental circulation. 863 42

The present study was designed to test the hypothesis that betamethasone may potentiate nitric oxide-mediated relaxation of coronary arteries of preterm lambs. Isolated coronary arteries were obtained from lambs delivered at 128 days gestation. The lambs were treated intramuscularly with a single dose of betamethasone or saline 48 h before delivery and were killed after 3 h of ventilation after delivery. Vessel rings were suspended in organ chambers filled with modified Krebs-Ringer solution (95% O2-5% CO2, 37 degrees C), and their isometric tension was recorded. The endothelium-dependent relaxation induced by bradykinin and calcium ionophore A23187 was greater in arteries from antenatal betamethasone-treated lambs than in arteries from control lambs. The relaxation was abolished by N omega-nitro-L-arginine. Nitric oxide induced a greater relaxation in vessels from antenatal betamethasone-treated lambs and in vessels preincubated with betamethasone than in vessels from controls. Coronary arteries from control and antenatal betamethasone-treated lambs relaxed similarly to 8-bromoguanosine 3',5'-cyclic monophosphate. Nitric oxide induced a greater increase in guanosine 3',5'-cyclic monophosphate content in coronary arteries from antenatal betamethasone-treated lambs than in arteries from control lambs. Our data suggest that antenatal betamethasone therapy potentiates nitric oxide-mediated relaxation in coronary arteries from preterm lambs, probably by affecting the activity of soluble guanylate cyclase of vascular smooth muscle cells.
...
PMID:Antenatal betamethasone therapy potentiates nitric oxide-mediated relaxation of preterm ovine coronary arteries. 877 28

In this study we tested the hypothesis that lactate, independent of changes in pH, can affect skeletal muscle blood flow through arteriolar dilation that may be mediated by guanosine 3',5'-cyclic monophosphate. Isolated, cannulated, and pressurized first-order rat cremaster skeletal muscle arterioles were studied in a chamber containing Krebs-bicarbonate buffer under no-flow conditions. At pH 7.4 and PO2 of 65 Torr, neutralized lactic acid (lactate) and pyruvic acid (pyruvate) caused arteriolar dilation over the 1-10 mM concentration range. This response to lactate was not altered by 10(-5) M indomethacin, 10(-4) M NG-nitro-L-arginine, or removal of the endothelium. However, responses to 1 and 3 mM pyruvate were significantly inhibited by 100% by endothelium removal, and the response to 10 mM pyruvate was inhibited by 71%. The relaxation of endothelium-denuded arterioles to lactate was inhibited by 10 microM methylene blue, 10 microM LY-83583, hypoxia (PO2 7-10 Torr), and diphenyliodonium, an inhibitor of superoxide-producing flavo-protein enzymes. In contrast, arteriolar dilation to the acidification of the Krebs buffer to pH 7.15, produced by increasing the CO2 concentration of the gas mixture from 5 to 10%, was not inhibited by methylene blue. These results are consistent with lactate-induced skeletal muscle arteriolar dilation being dependent on H2O2-mediated activation of vascular smooth muscle guanylate cyclase and independent of endothelium-derived mediators.
...
PMID:Evidence for cGMP mediation of skeletal muscle arteriolar dilation to lactate. 882 84

Because arginine analogues have been reported to block the vasodilator response to hypercapnia, we investigated the effect of nitro-L-arginine (L-NNA) on the dilation of pial arterioles to arterial hypercapnia induced by inhalation of 3, 5, and 7% CO2 in anesthetized cats equipped with cranial windows. L-NNA at 250 microM, but not at lower concentrations, significantly reduced hypercapnia-induced dilation. This effect could be reversed by L-arginine. However, hypercapnic hyperemia is not the result of increased guanosine 3',5'-cyclic monophosphate via the usual NO-mediated activation of guanylate cyclase, because application of LY-83583, which blocks guanylate cyclase, did not alter the vessel response to CO2. L-NNA at 250 microM also abolished the pial arteriolar dilation in response to cromakalim, minoxidil, and pinacidil, three known openers of ATP-sensitive K+ channels, and this effect could be reversed by L-arginine. Application of glyburide, which blocks ATP-sensitive K+ channels, also reduced the response to CO2. Subsequent application of L-NNA in these experiments had no additional effect. Vasodilation induced by sodium nitroprusside and 3-morpholinosydnonimine, two known NO donors, was unaffected by glyburide. NG-monomethyl-L-arginine had effects similar to those of L-NNA in the cat and rat at concentrations as low as 20 microM. Our findings suggest that arginine analogues inhibit hypercapnic vasodilation by blocking ATP-sensitive K+ channels, independently of activation of guanylate cyclase via increased production of NO. Furthermore, the data suggest that ATP-sensitive K+ channels may have an arginine site that influences their function.
...
PMID:Arginine analogues inhibit responses mediated by ATP-sensitive K+ channels. 889 45


<< Previous 1 2 3 4 5 Next >>

---