Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of nitric oxide in the uterotrophic action of oestradiol after 6 h or 72 h was studied in immature (19-21 days old) female Wistar rats by use of L-arginine, the amino acid from which nitric oxide is synthesized, and N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase. Oestradiol at single s.c. doses of 2.5, 5.0 and 10.0 micrograms per rat induced dose-dependent uterine oedema in 6 h. L-NAME (10 and 20 mg kg-1, i.p.) administered 30 min before oestradiol (10 micrograms per rat) injection suppressed the formation of uterine oedema in a dose-related manner. This action of L-NAME on oestradiol-induced uterine oedema was effectively blocked by pretreatment of rats with L-arginine (600 mg kg-1, s.c.), a precursor of nitric oxide, but not by L-lysine, an amino acid not involved in the generation of nitric oxide. In addition, L-NAME at similar doses significantly prevented oestradiol-induced (3 micrograms per rat, s.c. on three successive days) increases in uterine growth after 72 h; however, this effect was mitigated by L-arginine (600 mg kg-1). These results suggest the involvement of an L-arginine-nitric oxide system in the oestradiol-induced uterotrophic effect in immature rats.
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PMID:Nitric oxide synthase inhibition and the uterotrophic response to oestrogen in immature rats. 856 75

Estradiol-17beta (E2beta), a potent vasodilator, has its greatest effects on the uterine vasculature, blood flow (UBF) increasing > or = 10-fold. The mechanism(s) responsible for E2beta-induced vasodilation is unclear. We determined if nitric oxide (NO)-induced increases in cGMP modulate estrogen-induced increases in UBF, and if cyclooxygenase inhibition modifies E2beta responses. Nonpregnant (n = 15) and pregnant (n = 8) ewes had flow probes implanted on main uterine arteries and catheters in branches of the uterine vein and artery bilaterally for blood sampling and infusion of the NO synthase inhibitor L-nitro-arginine methyl ester (L-NAME), respectively. In nonpregnant ewes E2beta (1 microg/kg) caused parallel increases (P < 0.001) in UBF (15+/-3 to 130+/-16 ml/min) and uterine cGMP secretion (23+/-10 to 291+/-38 pmol/min); uterine venous cGMP also rose (4.98+/-1.4 to 9.43+/-3.2 pmol/ml; P < 0.001). Intra-arterial L-NAME partially inhibited increases in UBF dose-dependently (r = 0.66, n = 18, P < 0.003) while completely inhibiting cGMP secretion (P = 0.025). Indomethacin, 2 mg/kg intravenously, did not alter E2beta-induced responses. After E2beta-induced increases in UBF, intraarterial L-NAME partially decreased UBF dose dependently (r = 0.73, n = 46, P < 0.001) while inhibiting cGMP secretion (178+/-48 to 50+/-24 pmol/min; n = 5, P = 0.006); both were reversed by L-arginine. In pregnant ewes, E2beta increased UBF and venous cGMP (9.1+/-0.96 to 13.2+/-0.96 pmol/ml, P < 0.01); however, intraarterial L-NAME decreased basal cGMP secretion 66% (P = 0.02), but not UBF. Acute estrogen-induced increases in UBF are associated with NO-dependent increases in cGMP synthesis, but other mechanisms may also be involved. However, vasodilating prostanoids do not appear to be important. In ovine pregnancy NO is not essential for maintaining uteroplacental vasodilation.
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PMID:Nitric oxide contributes to estrogen-induced vasodilation of the ovine uterine circulation. 890 36

Short-term estrogen administration has been independently proposed to produce arterial vasodilation by both an indirect mechanism and a direct mechanism (inhibition of calcium entry though the L-type calcium channel). The proposed contributions of such diverse mechanisms to the vascular actions of 17beta-estradiol were examined in perfused hearts and in aortic ring sections isolated from female rabbits. In isolated rabbit hearts retrogradely perfused with Tyrode's solution, concentration-response curves to 17beta-estradiol (10(-9)-10(-5) M) were performed under control conditions and during perfusion with Bay K8644 (10(-7) M). 17beta-Estradiol produced a concentration-dependent decrease in coronary vascular resistance proportional to nitric oxide (NO) release in the presence and absence of Bay K8644. The addition of N(G)-nitro-L-arginine methyl ester (L-NAME; 10(-4) M) to the perfusate (a) completely inhibited NO formation, (b) produced a 2.3-fold and 1.55-fold rightward shift in the concentration-response curve to 17beta-estradiol for Bay K8644 treated and control hearts, respectively, and (c) failed to prevent coronary artery vasodilation. In isolated aortic rings contracted with Bay K8644, 17beta-estradiol (10(-5) M) relaxed both intact (58%) and denuded (54%) aortic rings. L-NAME (10(-4) M) completely blocked NO release in intact rings but did not prevent relaxation in denuded aortic rings. The data demonstrate (a) an endothelium-dependent relaxation by 17beta-estradiol, coincident with NO formation and suppressed by L-NAME, and (b) a direct relaxation of aortic and coronary smooth muscle independent of NO formation at higher 17beta-estradiol concentrations.
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PMID:Effect of 17-beta estradiol in the rabbit: endothelium-dependent and -independent mechanisms of vascular relaxation. 926 32

Estrogen induces the generation of nitric oxide (NO) and produces coronary vasodilation by opening the Ca2+-activated K+ (K[Ca]) channels. The hypothesis that 17beta-estradiol produces NO and activates K(Ca) channels during coronary hypoperfusion was investigated. In open-chest dogs, the left anterior descending coronary artery was perfused through an extracorporeal bypass tube from the left carotid artery. 17beta-Estradiol was infused into the bypass tube for 20 min after coronary blood flow was reduced by partial occlusion of the bypass tube. 17beta-Estradiol increased the difference in NO concentrations between the coronary venous and arterial blood as well as coronary blood flow. The lactate extraction ratio and pH of coronary venous blood were both also increased by 17beta-estradiol, indicating a reduction in myocardial anaerobic metabolism. Whereas the increase in the coronary arteriovenous difference in NO concentration was completely attenuated by N(G)-nitro-L-arginine methyl ester (L-NAME, an inhibitor of NO synthase), the increase in coronary blood flow induced by 17beta-estradiol was only partially attenuated by L-NAME. The combination of L-NAME and iberiotoxin (a blocker of high-conductance K(Ca) channels) completely abolished the coronary vasodilatory effect of 17beta-estradiol. The data indicate that during coronary hypoperfusion in canine hearts, 17beta-estradiol increases coronary blood flow and improves metabolic dysfunction by increasing NO release and opening K(Ca) channels.
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PMID:Roles of NO and Ca2+-activated K+ channels in coronary vasodilation induced by 17beta-estradiol in ischemic heart failure. 927 64

It has previously been demonstrated that uterine nitric oxide synthase (NOS) activity increases before embryonic implantation in rats. The aim of the present work was to investigate the regulation and the physiological relevance of the nitric oxide (NO) system in ovoimplantation. The increase in NOS activity in early pregnancy was found to be independent of the presence of embryos in the uterus. Whereas the Ca2+-dependent isoform of NOS increased gradually in the preimplantation days, the Ca2+-independent isoform increased just at the beginning of implantation (Day 5, 1800 hours); then the activity of both isoforms declined. Oestradiol, whose concentration peaks before implantation, might be regulating NOS activity in the uterus, since treatment of rats with tamoxifen, a receptor antagonist, reduces the activity of both isoforms to preimplantation levels. Intraluminal injections of L-NAME (0.5 mg kg[-1]), a competitive inhibitor of NOS, reduced by 50% the number of implanted embryos; this suggests that the NO system plays a role during implantation. The data suggest that oestradiol might be a modulator of NOS activity during nidation and that NO production is necessary to achieve a successful embryo implantation.
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PMID:Nitric oxide synthase regulation during embryonic implantation. 941 87

Previous reports correlate plasma levels of estrogen with increased nitric oxide (NO) production. To investigate whether the hemodynamic effects of estrogens are mediated by NO, we compared the hemodynamic changes induced by 17 beta-estradiol (100 micrograms/kg) in the absence and presence of the NO synthesis inhibitor N omega-nitro-L-arginine methyl ester (L-NAME). All protocols were performed in ovariectomized, conscious rats. Estradiol alone resulted in no significant changes in cardiac index (CI) or mean arterial pressure (MAP). However, in the presence of L-NAME, estradiol induced a significant increase in total peripheral resistance (TPR) of 37.3 +/- 11.7% and a decrease in CI of 27 +/- 4.9%, without changes in MAP. Previous blockade of angiotensin II AT1 receptors with losartan prevented any change in CI and TPR induced by 17 beta-estradiol in the presence of L-NAME. These observations suggest that NO is necessary to offset a vasoconstrictor action of angiotensin II, which is stimulated by estradiol administration.
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PMID:Hemodynamic effect of 17 beta-estradiol in absence of NO in ovariectomized rats: role of angiotensin II. 957 58

The effects of chronic 17beta-estradiol on endothelium-dependent relaxation to acetylcholine (ACh) and contraction to NG-nitro-L-arginine methyl ester (L-NAME), and endothelium-independent relaxation to sodium nitroprusside (SNP) were examined on blood vessels from rats with chronic heart failure (CHF). Two groups of ovariectomized female (50-60 days) rats were implanted with pellets containing 17beta-estradiol (25 microg/day) or vehicle, and given ligation of the left main coronary artery 1 week later. Another group of ovariectomized rats was implanted with vehicle pellets, and sham-operated. After 7 weeks, thoracic aortic rings, pulmonary artery rings, and portal vein strips were prepared for in vitro studies. Relative to sham-operated rats treated with the vehicle, vessels from vehicle-treated, coronary-ligated rats had similar relaxation to ACh and SNP but reduced response to L-NAME that was significant (P<0.05) for the aorta and portal vein but not pulmonary artery. Treatment of ligated rats with 17beta-estradiol augmented responses to L-NAME in the aorta, pulmonary artery and portal vein to values above those in sham-operated rat. 17beta-Estradiol did not affect relaxation of any vessels to SNP and increased maximum relaxation to ACh only in the portal vein. Hence, 17beta-estradiol enhances the relaxant role of basal nitric oxide in CHF.
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PMID:Chronic 17beta-estradiol augments relaxant role of basal nitric oxide in blood vessels from rats with heart failure. 987 27

The influence of the hormonal condition on the reactivity of central dopamine (DA) receptors was studied in male and in intact and ovariectomized (OVX) female rats. They were injected with selective DA agonists, acting either on D1 (SKF 38393, 2.5 or 10 mg/kg) or D2 receptors (PPHT, 31.3 or 125 microg/kg), or with selective DA antagonists, acting either on D1 (SCH 23390, 6.25 or 25 microg/kg), or D2 receptors (sulpiride, 10 or 40 mg/kg). The acquisition of an avoidance conditioning response (CAR) and the performance of some spontaneous motor behaviors were tested. Both D1 and D2 agonists and antagonists impaired the acquisition of CARs in diestrous, OVX, and male rats. Nevertheless, the effects of these drugs during estrus and in estradiol-primed OVX rats were different according to the drug and the dose injected. Whereas SKF 38393 failed to induce significative changes, PPHT and low doses of SCH 23390 and sulpiride improved the acquisition of CARS in those groups. The effects on conditioning were not accompanied with equivalent changes in spontaneous motor activity. Estradiol level fluctuations that occur in female rats within the estrous cycle or in OVX rats primed with estradiol would be responsive of changes in the response to DA agents. Although the reactivity of central DA systems is differentially affected by the hormonal condition of the rat, the precise mechanism of this modulatory action remains unknown.
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PMID:Behavioral effects of dopamine agonists and antagonists: influence of estrous cycle, ovariectomy, and estrogen replacement in rats. 997 41

17beta-Estradiol prevents early vascular lesion development and may also affect advanced atherosclerosis. To test the antiatherosclerotic effect of estrogen under conditions that resemble more advanced human atherosclerosis with severe endothelial dysfunction, we have investigated the effect of 17beta-estradiol in hypercholesterolemic rabbits treated with the nitric oxide synthase inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME). Chronic L-NAME administration attenuated endothelial nitric oxide (EDNO)-mediated vascular responses leading to significantly accelerated atherosclerotic plaque development. 17beta-Estradiol treatment alone inhibited aortic lesion formation with concurrent increase in EDNO-mediated responses. The beneficial effect of estrogen persisted in the L-NAME-treated rabbits, suggesting that the antiatherogenic action of 17beta-estradiol involves NO-independent mechanisms as well. Serum cholesterol levels were not altered by any of the treatments. 17beta-Estradiol treatment significantly increased EDNO production under these conditions as well. The reduction in plaque size by 17beta-estradiol was always accompanied by increased EDNO production, suggesting a strong association between these two events. The results demonstrate that estrogen treatment may exert protection against atherosclerosis even in patients with severe endothelial dysfunction.
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PMID:Effect of 17beta-estradiol in hypercholesterolemic rabbits with severe endothelial dysfunction. 1033 Feb 64

The nuclear orphan receptor CAR (constitutively active receptor or constitutive androstane receptor) can be activated in response to xenochemical exposure, such as activation by phenobarbital of a response element called NR1 found in the CYP2B gene. Here various steroids were screened for potential endogenous chemicals that may activate CAR, using the NR1 enhancer and Cyp2b10 induction in transfected HepG2 cell and/or in mouse primary hepatocytes as the experimental criteria. 17beta-Estradiol and estrone activated NR1, whereas estriol, estetrol, estradiol sulfate, and the synthetic estrogen diethylstilbestrol did not. On the other hand, progesterone and androgens repressed NR1 activity in HepG2 cells, and the repressed NR1 activity was fully restored by estradiol. Moreover, estrogen treatment elicited nuclear accumulation of CAR in the mouse livers, as well as primary hepatocytes, and induced the endogenous Cyp2b10 gene. Ovariectomy did not affect either the basal or induced level of CAR in the nucleus of the female livers, while castration slightly increased the basal and greatly increased the induced levels in the liver nucleus of male mice. Thus, endogenous estrogen appears not to regulate CAR in female mice, whereas endogenous androgen may be the repressive factor in male mice. Estrogen at pharmacological levels is an effective activator of CAR in both female and male mice, suggesting a biological and/or toxicological role of this receptor in estrogen metabolism. In addition to mouse CAR, estrogens activated rat CAR, whereas human CAR did not respond well to the estrogens under the experimental conditions.
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PMID:Estrogen activation of the nuclear orphan receptor CAR (constitutive active receptor) in induction of the mouse Cyp2b10 gene. 1107 20


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