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)

Previous investigators have identified an aortic-to-radial artery pressure gradient thought to develop during rewarming and discontinuation of cardiopulmonary bypass. The authors measured mean aortic and radial artery pressures before, during, and after cardiopulmonary bypass in 30 patients, to determine when the pressure gradient develops. The pressure gradient was also measured before and after intravenous injections of sodium nitroprusside (1 microgram/kg) and phenylephrine (7 micrograms/kg) to determine the effect of changes in systemic vascular resistance. A significant (P less than 0.05) pressure gradient (mean +/- SEM = 4.9 +/- 0.7 mmHg) developed upon initiation of cardiopulmonary bypass. This gradient did not change significantly during the middle of bypass (4.2 +/- 0.5 mmHg), with rewarming (4.8 +/- 0.7 mmHg), immediately prior to discontinuation of bypass (4.6 +/- 0.7), or 5 and 10 min following bypass (4.9 +/- 0.9 and 4.8 +/- 0.7 mmHg). Sodium nitroprusside significantly decreased systemic vascular resistance, by 15 +/- 2%, during the middle of bypass but did not affect the pressure gradient. Likewise, phenylephrine increased the systemic vascular resistance by 52 +/- 6% and 34 +/- 4% during the middle of bypass and rewarming, respectively, without affecting the pressure gradient. Although the exact mechanisms responsible for the pressure gradient remain unknown, these results suggest its etiology is associated with events occurring during initiation of cardiopulmonary bypass rather than with rewarming or discontinuation of cardiopulmonary bypass.
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PMID:Differences between aortic and radial artery pressure associated with cardiopulmonary bypass. 161 10

The hemodynamic effects of prostaglandin E1, sodium nitroprusside (SNP), nitroglycerin, and hydralazine were studied in a porcine model of elevated pulmonary vascular resistance (PVR) due to glass bead microembolization (60-150-microns diameter). Each animal received all four drugs. Each drug was titrated to produce a 30% reduction in mean systemic arterial pressure. Although all four drugs decreased PVR, distinct differences in the hemodynamic profiles of the four drugs were evident. Prostaglandin E1 produced the largest reduction in mean pulmonary artery pressure (from 41 +/- 1 to 32 +/- 9 mm Hg, mean +/- SEM) and PVR (25 +/- 3 to 18 +/- 2 mm Hg.L-1.min-1), and did not affect the ratio of PVR to systemic vascular resistance (PVR/SVR). Sodium nitroprusside and nitroglycerin produced moderate decreases in PVR (nitroglycerin 21 +/- 2 to 18 +/- 2 mm Hg.L-1.min-1, SNP 22 +/- 2 to 19 +/- 2 mm Hg.L-1.min-1) and in mean pulmonary artery pressure (nitroglycerin 39 +/- 1 to 35 +/- 1; SNP 40 +/- 1 to 36 +/- 2 mm Hg). Both drugs significantly increased the PVR/SVR ratio. Hydralazine was the only drug that significantly increased cardiac output (1.6 +/- 0.2 to 1.9 +/- 0.3 L/min). Hydralazine had no significant effect on mean pulmonary artery pressure, reduced PVR to the smallest extent (11%), and resulted in the largest increase in the PVR/SVR ratio (from 0.52 +/- 0.04 to 0.80 +/- 0.08). In this model of increased pulmonary vasculature resistance prostaglandin E1 caused an equivalent amount of pulmonary and systemic vasodilation, as expressed by the PVR/SVR ratio.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Vasodilator therapy in microembolic porcine pulmonary hypertension. 211 65

Attenuated cholinergic vasodilatation has been suggested as an endothelium-related mechanism involved in essential hypertension. We investigated the role of muscarinic (M) receptor subtypes in the forearm resistance vasculature. In eight white men with essential hypertension and eight matched normotensive control subjects (age of both groups, 47 +/- 4 years; mean +/- SEM), we infused the nonselective agonist methacholine in the presence of saline and the antagonists atropine (nonselective), pirenzepine (M1-selective), and AF-DX 116 (M2-selective) into the brachial artery and measured forearm blood flow and forearm vascular resistance using venous occlusion plethysmography. Affinity constants (pKb values) were determined from calculated plasma concentrations of the infused compounds and EC50 values. Sodium nitroprusside was given as an endothelium-independent control, and minimal forearm vascular resistance after 10 minutes of ischemia was used as a marker of structural vascular changes. Hypertensive patients showed higher minimal forearm vascular resistance, indicating structural vascular changes. However, sodium nitro-prusside- and methacholine-induced vasodilatation was similar in both groups, with apparent EC50 values (log moles per liter; mean +/- SEM) of -7.32 +/- 0.13 and -7.51 +/- 0.21 in hypertensive patients and -7.37 +/- 0.13 and -7.45 +/- 0.02 in control subjects, respectively. Atropine, pirenzepine, and AF-DX 116 caused a shift to the right of the concentration-response curve of methacholine, with apparent pKb values of 8.63 +/- 0.08, 6.81 +/- 0.13, and 5.51 +/- 0.29 in hypertensive individuals and 8.62 +/- 0.10, 6.98 +/- 0.08, and 5.49 +/- 0.09 in control subjects, respectively. Again, there were no statistically significant differences in these pharmacological parameters between hypertensive patients and normotensive subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In vivo characterization of muscarinic receptor subtypes that mediate vasodilatation in patients with essential hypertension. 760 35

We examined the effects of exogenous nitric oxide (NO) on prostaglandin production in fetal ovine astroglia. Astroglia in secondary culture grown in 12 well plates were exposed to medium alone or medium containing 10 ng/ml interleukin 1 alpha (IL1 alpha), in the presence or absence of 10 and 100 microM sodium nitroprusside (SNP). Sodium nitroprusside is a NO donor. Prostaglandin F2 alpha (PGF2 alpha) levels were determined by enzyme immunoassay after 4 h of medium and/or drug application. Application of 100 microM SNP reduced basal levels of PGF2 alpha from 530 +/- 48 pg/ml (mean +/- SEM) (n = 9) to 248 +/- 60 pg/ml (n = 8) (P < 0.05). In IL1 alpha treated cells, PGF2 alpha levels were 846 +/- 109 pg/ml (n = 9) (P < 0.05, compared to basal levels) in the absence and 567 +/- 122 pg/ml (n = 9) in the presence of 100 microM SNP (P < 0.05, compared to IL1 alpha alone). We tested whether effects of exogenous NO on PGF2 alpha levels would be influenced by elimination of endogenously produced NO. Inhibition of NO synthase with 100 microM NG-nitro-L-arginine-methyl ester (L-NAME) did not affect PGF2 alpha levels during basal conditions, or affect reductions in PGF2 alpha levels during application of 100 microM SNP. In addition, L-NAME application did not affect IL1 alpha-induced increase in PGF2 alpha levels or reductions in PGF2 alpha levels with coapplication of 100 microM SNP. In contrast to the higher dose, application of 10 microM did not significantly affect PGF2 alpha levels. In summary, application of 100 microM SNP reduces basal production of PGF2 alpha and attenuates increases in PGF2 alpha levels with IL1 alpha application.
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PMID:Modulation of prostaglandin production by nitric oxide in astroglia. 917 71

Stimulated release of vasodilator prostaglandins and nitric oxide by angiotensin II may counteract the vasoconstrictor effects of this octapeptide. We investigated the effects of inhibition of prostaglandin synthesis by indomethacin and of nitric oxide formation by NG-monomethyl-L-arginine (L-NMMA) on baseline forearm blood flow (FBF) and on angiotensin II-induced vasoconstriction in healthy subjects. For comparison, the effects of the AT1-receptor antagonist losartan on these parameters were determined. FBF was measured by venous occlusion plethysmography. Angiotensin II (0.01-10 ng/kg/min) was infused into the brachial artery, in the absence and presence of indomethacin (0.65 micrograms/kg/min; n = 8), L-NMMA (30 micrograms/kg/min; n = 5), and losartan (3 micrograms/kg/min; n = 12), respectively. Sodium nitroprusside was used to submaximally predilate the forearm vascular system. Baseline FBF remained unchanged with indomethacin and losartan, but was significantly decreased by -42 +/- 6% (mean +/- SEM) by L-NMMA. The dose-dependent angiotensin II-induced vasoconstriction was unaffected by indomethacin and L-NMMA, but was inhibited by losartan. Emax was -78 +/- 2% during control conditions, -84 +/- 3% during indomethacin (n.s.), -74 +/- 4% during L-NMMA (n.s.), and -17 +/- 6% during losartan infusion (p < 0.05). None of the interventions significantly changed the EC50 value of angiotensin II of -9.4 +/- 0.14 log M. In conclusion, in the human forearm of healthy subjects, neither endogenous angiotensin II nor cyclooxygenase-dependent prostaglandin synthesis plays a role in the genesis of vascular tone, whereas endogenous nitric oxide production does. The constrictor effects of angiotensin II are counteracted by neither stimulated release of prostaglandins nor by that of nitric oxide.
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PMID:Influence of indomethacin and L-NMMA on vascular tone and angiotensin II-induced vasoconstriction in the human forearm. 935 98

Female sex hormones have been implicated in the cardioprotection of premenopausal women. However, the cardiovascular actions of these hormones and the effects of their natural fluctuations during the menstrual cycle are not fully understood. We studied changes in vascular function during the menstrual cycle in 15 healthy premenopausal women. Four noninvasive procedures were performed during the early follicular (EF), late follicular (LF), early luteal (EL), and late luteal (LL) phases: flow-mediated dilatation (FMD) of the brachial artery during reactive hyperemia, laser Doppler velocimetry (LDV) with direct current iontophoresis of acetylcholine (ACh) and nitroprusside, whole body arterial compliance (WBAC), and pulse wave velocity. Hormone levels were consistent with predicted cycle phase and showed that all subjects ovulated during the cycle studied. FMD, LDV with ACh, and WBAC varied cyclically, with significant increases from the F to LF phase, sharp falls in the EL phase, and significant recoveries in the LL phase. These changes were most marked for FMD [EF, 8.8 +/- 0.6% (mean +/- SEM); LF, 10.0 +/- 0.7; EL, 4.2 +/- 0.6; LL, 8.6 +/- 0.9] and the LDV response to ACh (EF, 2.7 +/- 0.2 V/min; LF, 3.3 +/- 0.4; EL, 1.8 +/- 0.3; LL, 2.7 +/- 0.4). WBAC changed similarly (EF, 0.58 +/- 0.08 arbitrary units; LF, 0.84 +/- 0.06; EL, 0.65 +/- 0.05; LL, 0.68 +/- 0.06). Sodium nitroprusside-induced vasodilatation decreased significantly from EF to EL, with no other significant difference, and pulse wave velocity did not vary significantly over the four time points. Conductance and resistance artery endothelial reactivity and smooth muscle sensitivity to nitric oxide and arterial compliance are modulated significantly in response to the changing hormonal patterns of the menstrual cycle. These findings emphasize the importance of menstrual phase in the interpretation of data on endothelial function and may provide insights into the mechanisms underlying sex differences in cardiovascular risk and other disease processes in premenopausal women.
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PMID:Variations in endothelial function and arterial compliance during the menstrual cycle. 1170 12

We investigated the effect of angiotensin II on intracellular cyclic GMP content and neurite outgrowth as an indicator of cell differentiation in PC12 W cells. Neurite outgrowth was examined by phase-contrast microscopy. Outgrown neurites were classified as small, medium and large, and were expressed as neurites per 100 cells. Angiotensin II (10-7 m) increased the outgrowth of medium and large neurites by mean +/- SEM 20.2 +/- 2.3 and 6.6 +/- 1.4 compared with 1.66 +/- 0.5 and 0.1 +/- 0.06 neurites per 100 cells in control. Cellular cyclic GMP content increased by 50-250% with angiotensin II at concentrations of 10-6-10-4 m. Both blockade of AT2 receptors and of nitric oxide synthase markedly reduced angiotensin II-induced neurite outgrowth and cyclic GMP production. In contrast, B2 receptor blockade had no effect or even increased these angiotensin II effects. Sodium nitroprusside and 8-bromo-cyclic GMP both mimicked the effects of angiotensin II on cell differentiation. The protein kinase G inhibitor KT-5823 inhibited the neurite outgrowth induced by both angiotensin II and 8-bromo-cyclic GMP. Our results demonstrate that angiotensin II can stimulate cell differentiation in PC12 W cells by nitric oxide-related and cyclic GMP-dependent mechanisms. The effects of angiotensin II on cell differentiation and cyclic GMP production were mediated via the AT2 receptor and further enhanced by bradykinin B2 receptor blockade.
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PMID:Contribution of bradykinin and nitric oxide to AT2 receptor-mediated differentiation in PC12 W cells. 1269 2

Vascular responsiveness to exogenous nitrates in type 2 diabetes (T2DM) is attenuated in brachial and coronary vessels. We determined platelet responsiveness to nitric oxide (NO) in T2DM and control subjects. We examined whether the postprandial (PP) state affected platelet sensitivity to NO donors in T2DM patients and the extent of correlation between this and measures of oxidative stress, compared to changes in endothelial function. Twelve T2DM subjects were studied fasting and four hours after a test meal and compared with 15 healthy controls. We assessed the inhibitory effects of NO donors on adenosine 5'-diphosphate (ADP)-induced platelet aggregation. Oxidative stress was assessed by lipid-derived free radicals, ex vivo by electron paramagnetic resonance spectroscopy and markers of lipid peroxidation. Endothelial function was assessed by flow-mediated vasodilatation (FMD) of the brachial artery. Results are expressed as (mean +/- SEM). Fasting platelet aggregation was increased in diabetics versus controls (14.86 +/- 1.1 Ohms vs. 10.76 +/- 1.1 Ohms, p < 0.05). Sodium nitroprusside (SNP) and glyceryl trinitrate (GTN) inhibited ADP-induced aggregation by 73.1 +/- 5.9% and 50.3 +/- 7.7% in healthy controls compared to 15.4 +/- 7% and 19.5 +/- 8.2% in T2DM (p < 0.05). Fasting and postprandial inhibition of platelet aggregation with NO donors in T2DM was similar. T2DM patients had higher levels of oxidative stress in the fasting state and postprandially. There were no PP correlations with platelet NO resistance. In conclusion, there is platelet hyporesponsiveness to NO donors (SNP/GTN) in T2DM compared to controls, with increased ADP-induced platelet aggregation. Platelet abnormalities were associated with increased oxidative stress.
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PMID:Platelet nitrate responsiveness in fasting and postprandial type 2 diabetes. 1630 64