UMLS:C0406810 - FACTA Search

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 objective of this study is to investigate whether the L-arginine/nitric oxide pathway is involved in the neurotransmission of paraventricular nucleus of hypothalamus (PVN) activation-induced penile erection in the rat. Male adult Sprague-Dawley rats anesthetized with pentobarbital were used. The femoral artery was cannulated to measure systemic and mean arterial pressure (SAP and MAP), and heart rate (HR). A 26-gauge needle was inserted into corpus cavernosum to measure the intracavernous pressure (ICP) simultaneously with SAP, MAP and HR on a polygraph. Four groups of study were arranged: (1) stereotaxically delivery of L-arginine (500 nmol/500 nl) into PVN; (2) administration of a mixture (1 microl) containing N(G)-Nitro-L-arginine methyl ester (L-NAME) 500 nmol and L-arginine 500 nmol into PVN; (3) microinjection of saline 500 nl into PVN as a vehicle control; and (4) intracavernous injection of L-arginine (100 nmol/50 microl). The ICP, SAP, MAP and HR were monitored for at least 2 h after each administration of the experimental agents. Upon administration of L-arginine into PVN, there was a significant increase of ICP from resting 9.6+/-2.5 mmHg to peaked at 64.4+/-9.8 mmHg after a latency of 3016.0+/-1749.7 s and with a duration of 27.6+/-15.8 min. There was no change of resting ICP after administration of the mixture of L-NAME and L-arginine into PVN. Application of saline to PVN and intracavernous injection of L-arginine failed to increase ICP. Based on elicitation of penile erection upon administration of L-arginine into PVN, and elimination of this L-arginine induced penile erection by co-administration of L-NAME with L-arginine, the results of this study suggest that L-arginine/nitric oxide pathway may be involved in the neurotransmission of PVN activation-induced penile erection in the rat.
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PMID:Involvement of L-arginine/nitric oxide pathway at the paraventricular nucleus of hypothalamus in central neural regulation of penile erection in the rat. 1205 40

The objective of the present study was to determine the contribution of the autonomic nervous system and nitric oxide to the depressor effect produced by unilateral microinjection of ANG-(1-7) and ANG II into the caudal ventrolateral medulla (CVLM). Unilateral microinjection of ANG-(1-7), ANG II (40 pmol), or saline (100 nl) was made into the CVLM of male Wistar rats anesthetized with urethane before and after intravenous injection of 1) methyl-atropine, 2.5 mg/kg; 2) prazosin, 25 microg/kg; 3) the nitric oxide synthase (NOS) inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), 5 mg/kg; or 4) the specific inhibitor of neuronal NOS, 7-nitroindazole (7-NI), 45 mg/kg. Arterial pressure and heart rate (HR) were continuously monitored. Microinjection of ANG-(1-7) or ANG II into the CVLM produced a significant decrease in mean arterial pressure (MAP; -11 +/- 1 mmHg, n = 12 and -10 +/- 1 mmHg, n = 10, respectively) that was not accompanied by consistent changes in HR or in cardiac output. The effect of ANG-(1-7) was abolished after treatment with methyl-atropine (-3 +/- 0.6 mmHg, n = 9) or L-NAME (-2.3 +/- 0.5 mmHg, n = 8) or 7-NI (-2.8 +/- 0.6 mmHg, n = 5). In contrast, these treatments did not significantly interfere with the ANG II effect (-10 +/- 2.6 mmHg, n = 8; -8 +/- 1.5 mmHg, n = 8; and -12 +/- 3.6 mmHg, n = 6; respectively). Peripheral treatment with prazosin abolished the hypotensive effect of ANG-(1-7) and ANG II. Microinjection of saline did not produce any significant change in MAP or in HR. These results suggest that the hypotensive effect produced by ANG II at the CVLM depends on changes in adrenergic vascular tonus and, more importantly, the hypotensive effect produced by ANG-(1-7) also involves a nitric oxide-related mechanism.
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PMID:Hypotensive effect of ANG II and ANG-(1-7) at the caudal ventrolateral medulla involves different mechanisms. 1237 12

The role of renal nerves on renal and cardiovascular responses to adenosine administration and/or acute NO synthase inhibition was investigated. Conscious male Wistar rats with implanted catheters in femoral artery for blood pressure registration, femoral vein for drug infusion and bladder for urine collection were used. Adenosine was applied i.v. (1.0 mg/kg BW bolus) followed by infusion of 0.1 mg/kg.min, and/or nitric oxide synthase inhibition (NOSI) was performed by i.v. administration of 10 mg/kg BW N-Omega-nitro-L-arginine methyl ester (L-NAME) before and 1 week after bilateral renal denervation (BRD). NOSI decreased HR and increased SAP, MAP and DAP both in intact and BRD rats. Baroreflex sensitivity increased in intact and BRD rats. Adenosine did not change HR, blood pressure or baroreflex sensitivity in intact as well as BRD rats. NOSI increased V, VU(Na) and VU(CI) in intact rats but decreased V and did not alter VU(Na) and VU(CI) in BRD rats. Adenosine increased V, VU(CI) and C(cr) in intact rats but did not change renal excretory function in BRD rats. Combined application of adenosine and L-NAME led to a dramatic increase of V, VU(Na), VU(Cl) and C(cr) in intact rats. However, VU(Na) and VU(CI) in BRD rats were lower as compared to intact rats. Therefore, changes in renal excretory function seen after NOSI are not exclusively the result of pressure diuresis and natriuresis but in some way are dependent on renal nerves. Renal denervation attenuates the renal excretory response to adenosine. Sympathetic nervous system is important in mediating the effects of adenosine and/or NO on renal excretory function. Renal denervation did not change the pattern of baroreflex sensitivity after adenosine and/or L-NAME administration.
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PMID:Renal and cardiovascular effects of renal denervation in conscious rats after adenosine administration and nitric oxide synthase inhibition. 1242 23

We examined the hypothesis that gender differences exist in platelet and vascular reactivity in type-2 diabetes mellitus, using Zucker fatty diabetic rats of both sexes and their lean littermates. Type-2 diabetes is characterized by excessive platelet production of TXA(2), which is thrombogenic. Testosterone up-regulates platelet TXA(2) receptors and the aggregation response to thromboxane mimetics. Conversely, estrogen increases vascular nitric oxide (NO) production and inhibits platelet aggregation. Hemodynamic studies were undertaken with the determination of dose-response curve for MAP and renal cortical blood flow (RCF) in response to U46619, angiotensin-II, phenylephrine and endothelin-1, as well as the systemic hemodynamic response to acetylcholine and L-NG nitro-arginine methylester (L-NAME). Platelet aggregation response was evaluated using whole blood impedance aggregometry. There were significant gender differences in the systemic blood pressure and RCF response to TXA(2)-mimetic U46619 and angiotensin-II (P<0.02, ANOVA) but not to phenylephrine or endothelin-1. Male rats exhibited a paradoxical hypotensive response to U46619 (-18+/-11 mmHg) compared with a peak pressor response of +6+/-1 mmHg in female rats (P<0.01, ANOVA). The male rats exhibited an attenuated systemic vasodilator response (P<0.001, ANOVA) to acetylcholine (fall in MAP in male diabetic rats being -24+/-8 mmHg, compared with a fall of -50+/-8 mmHg in females), but a greater rise in the renal cortical resistance in response to NO inhibition by L-NAME (P<0.03) compared with the female rats. Both the slope (46+/-2) and the peak magnitude of the U46619-induced whole blood platelet aggregation (13+/-1) ohms were significantly higher (P<0.01, ANOVA) in male (n=10) compared with female diabetic rats (n=8) (29+/-0.8 slope, 10.0+/-0.8 ohms, respectively). Thus, the male diabetic Zucker rats exhibited an impaired response to vasoconstrictors (U46619 and angiotensin-II) and to endothelial (NO)-mediated vasodilation. The male gender may therefore be associated with the greater prothrombotic activity and a worse impairment of endothelial reactivity in the type-2 diabetic state.
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PMID:Gender difference in vascular and platelet reactivity to thromboxane A(2)-mimetic U46619 and to endothelial dependent vasodilation in Zucker fatty (hypertensive, hyperinsulinemic) diabetic rats. 1248 37

We have reported that glucose infusion in L-NAME-treated rats increased arterial pressure more than the additive responses to glucose and L-NAME alone. This suggested that nitric oxide synthesis inhibition potentiated the hypertensive response to chronic glucose infusion, and the heart rate data suggested an important role for the sympathetic nervous system. This study tested the role of the sympathetic nervous system by infusing glucose for 7 days in 4 groups of rats: L-NAME (L), L-NAME plus alpha- and beta-adrenergic receptor blockade (LB), vehicle, or vehicle plus adrenergic receptor blockade (blockers). Mean arterial pressure (MAP, 24 hours per day) increased significantly in both the vehicle and blockers groups, confirming our previous reports. Likewise, MAP increased significantly more during glucose infusion in the L rats, from 120+/-3 mm Hg to 158+/-4 mm Hg by day 7, which was >3 times the increase in the vehicle rats. Heart rate also increased significantly in the L rats, from 391+/-4 to 426+/-8 bpm, and that increase was prevented completely in the LB rats. However, although the increase in MAP in the LB rats was significantly less than in the L rats, the hypertension was not prevented completely. The explanation for that partial inhibition is not clear, but the overall effectiveness of adrenergic receptor blockade to attenuate the potentiated hypertensive and tachycardic responses to glucose infusion in the L-NAME-treated rats versus the normal rats suggests that nitric oxide may help protect against hypertension during glucose infusion through suppression of sympathetic activity.
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PMID:Nitric oxide opposes glucose-induced hypertension by suppressing sympathetic activity. 1257 94

Superficial vein pathology involves both mechanical (hyperpressure and distension) and inflammatory mechanisms. Conflicting results exist about the role of NO in the venous hyporeactivity induced by inflammation. In order to clarify this point, we aimed to investigate the effects of sepsis on cutaneous vein responsiveness in vivo and the possible contributions of constitutive and inducible NOS to the changes of venous contractility. Saphenous vein diameter was recorded by an ultrasonic echo-tracking device in pentobarbital-anaesthetised rabbits. Bacterial lipopolysaccharide (LPS) was administered i.v. at 20 mg/kg/15 min, inducing a progressive fall in mean arterial blood pressure after 2-3 h. The effects of LPS on saphenous vein responsiveness to noradrenaline (2 microg/kg i.v.) were measured simultaneously. In some rabbits, veins were removed for immunochemistry to detect iNOS staining. The venoconstriction to noradrenaline was already significantly reduced at 30 min after LPS (6+/-1% instead of 19+/-1% before LPS) and was completely abolished 3 h after LPS. A reduction of the venoconstriction induced by sumatriptan, a 5-HT(1B/D) agonist, (100 microg/kg, 11+/-1% after saline n=5) was also observed 180 min after LPS infusion (3+/-1%, n=4). The venodilatations induced by acetylcholine or sodium nitroprusside injected locally into the vein were not altered by LPS. When administered 90 min after LPS infusion, the NOS inhibitor L-NAME but not the selective iNOS inhibitor L-NIL (10 mg/kg) induced a recovery of the venoconstriction. Preventive perfusion with L-NAME (10 mg/kg/2 h) reduced the initial hyporeactivity to noradrenaline (30 to 60 min), but accelerated the lethal fall in MAP. L-NIL (10 mg/kg/2 h), to a lesser extent than L-NAME, also reduced the initial hyporeactivity to noradrenaline; in contrast to L-NAME, L-NIL also delayed the complete loss of noradrenaline constriction and improved animal survival. In control animals, neither L-NAME nor L-NIL modified the venoconstriction induced by noradrenaline. iNOS staining was observed in the saphenous vein endothelium after LPS. The experimental model developed in these experiments allows the study of venous responsiveness during sepsis in vivo. Our results show that LPS administration reduces saphenous vein contractility to both adrenergic and serotoninergic constrictor agents. The data suggest that both endothelial and inducible NO are involved in the loss of venous reactivity but these enzymes exert contrasting effects on blood pressure changes.
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PMID:Cutaneous venous dysfunction studied in vivo in the LPS-treated rabbit: implication of NO in saphenous vein hyporeactivity. 1267 58

The dependence of blood pressure on a balance between superoxide and nitric oxide may be amplified in diabetes. We have shown that the first occurrence of sustained hyperglycemia in type I diabetes causes hypertension when induced in rats that have had nitric oxide synthesis blocked chronically (L-NAME, 10 microg/kg per minute IV). This study used tempol (18 micromol/kg per hour IV) to test the hypothesis that superoxide mediates that hypertensive response. Induction of diabetes in untreated rats had no significant effect on mean arterial pressure (MAP, measured 18 h/d), and glomerular filtration rate (GFR) increased significantly during the 2 weeks of diabetes. Chronic infusion of L-NAME in a separate group of rats increased baseline MAP from approximately 90 mm Hg to a stable level of approximately 120 mm Hg after 6 days of infusion, and induction of diabetes (streptozotocin, 40 mg/kg IV) in those rats caused a rapid, progressive increase in MAP that averaged 156+/-5 mm Hg by day 14 of diabetes that was associated with a decrease in GFR and 4-fold increase in isoprostane excretion. Tempol infusion was begun on day 2 of diabetes in a subgroup of those rats, and the progressive hypertensive response was prevented, with MAP averaging 134+/-10 mm Hg by day 14. In addition, the normal renal hyperfiltration response was restored by tempol and the increase in isoprostane did not occur. Thus, the hypertension and decrease in GFR caused by onset of diabetes in rats without a functioning nitric oxide system was prevented by chronic administration of the superoxide dismutase mimetic tempol.
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PMID:Nitric oxide may prevent hypertension early in diabetes by counteracting renal actions of superoxide. 1465 52

We hypothesized that the effective inhibition of nitric oxide synthase (NOS), achieved via systemic infusion of N(G)-nitro-l-arginine methyl ester (l-NAME), would reduce the gas exchange threshold (GET) and the maximal oxygen uptake (V(.)(O(2)max)) during incremental cycle exercise in man if NO is important in the regulation of muscle vasodilatation. Seven healthy males, aged 18-34 years, volunteered to participate in this ethically approved study. On two occasions, the subjects completed an incremental exercise test to exhaustion on an electrically braked cycle ergometer following the infusion of either l-NAME (4 mg kg(-1) in 50 ml saline) or placebo (50 ml saline, CON). At rest, the infusion of l-NAME resulted in a significant increase in mean arterial pressure (MAP; CON vs. l-NAME, 89 +/- 8 vs. 103 +/- 11 mmHg (mean +/- s.d.; P < 0.05)) and a significant reduction in heart rate (HR; CON vs. l-NAME, 60 +/- 12 vs. 51 +/- 8 beats min(-1); P < 0.01). At submaximal work rates, there was no significant difference in V(.)(O(2)) between the conditions and no difference in the GET (CON vs. l-NAME, 1.94 +/- 0.47 vs. 2.01 +/- 0.41 l min(-1)). However, at higher work rates, differences in V(.)(O(2)) between the conditions became more pronounced such that V(.)(O(2)max) was significantly lower with l-NAME (CON vs. l-NAME, 4.02 +/- 0.41 vs. 3.80 +/- 0.34 l min(-1); P < 0.05). The reduction in V(.)(O(2)max) was associated with a reduction in HR(max) (CON vs. l-NAME, 186 +/- 10 vs. 178 +/- 7 beats min(-1); P < 0.01). These results demonstrate that NOS inhibition with l-NAME has no effect on GET but reduces V(.)(O(2)max) during large muscle group exercise in man, presumably by direct or indirect effects on cardiac output and muscle blood flow.
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PMID:Nitric oxide synthase inhibition with L-NAME reduces maximal oxygen uptake but not gas exchange threshold during incremental cycle exercise in man. 1528 44

This study was designed to determine if the thyroid hormone analog 3,5 diiodothyropropionic acid (DITPA), now in clinical trials for heart failure, alters endothelial function after myocardial infarction (MI). Three weeks after MI, adult Sprague-Dawley rats were randomly assigned to DITPA (375 microg/100 g subcutaneous) or no treatment of 3 weeks. In MI rats, left ventricular (LV) end-diastolic pressure and LV dP/dt decreased (P < 0.05). DITPA did not change MAP (87 +/- 10 versus 90 +/- 7 mm Hg) or LV end-diastolic pressure (23 +/- 3 versus 19 +/- 9 mm Hg) but did lower (P < 0.05) LV dP/dt (4,633 +/- 797 versus 3,650 +/- 1,236 mm Hg/s). In aortic segments from MI rats, DITPA enhanced the acetylcholine dependent vasorelaxation (59 +/- 11% at 10(-4) M, P < 0.05) and isoproterenol induced vasorelaxation (57 +/- 13% at 10(-4) M, P < 0.05). The increases in vasorelaxation were blocked with l-NAME and restored with L-arginine. Treatment with DITPA increased (P < 0.05) eNOS protein content in aortic tissue from sham rats (3.8 +/- 2.8 to 44.5 +/- 7.1 integrated intensity units (II)/microg) and in MI rats (5.3 +/- 3.4 to 28.3 +/- 8.9 II/microg). In endothelial cells, 24 hours' treatment with DITPA (10 microM) increased (P < 0.01) eNOS protein expression from 22.1 +/- 4.8 to 52.7 +/- 16.8 II/microg protein and DITPA (20 microM) increased eNOS to 49.1+/- 15.2 II/microg protein. The thyroid analog DITPA enhances endothelial nitric oxide and beta-adrenergic-mediated vasorelaxation by increasing nitric oxide in the vasculature.
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PMID:Thyroid hormone analog, DITPA, improves endothelial nitric oxide and beta-adrenergic mediated vasorelaxation after myocardial infarction. 1545 53

We evaluated the cardiovascular effects of nitric oxide (NO) inhibitors microinjected into the rostral ventrolateral medulla (RVLM) of conscious rats. Application of L-NAME or aminoguanidine (AG) induced an increase in arterial blood pressure (MAP) and an increase in heart rate, whereas 7-nitroindazole (7-NI) decreased MAP and HR. Microinjection of glutamate produced an increase in MAP which was followed by either a tachycardia or a bradycardia. Such responses were blocked totally by prior administration of L-NAME and attenuated (approximately 50%) by 7-NI. In contrast, glutamate responses were enhanced by following AG. We conclude that in conscious rats, NO has tonic effects in the RVLM and may participate in the modulation of the actions of glutamate through iNOS and nNOS pathways.
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PMID:Differential influence of iNOS and nNOS inhibitors on rostral ventrolateral medullary mediated cardiovascular control in conscious rats. 1690 70

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