Nitric oxide does not mediate the vasodilation of early human pregnancy

Background: In early pregnancy, a substantial drop in arterial blood pressure occurs, that might be attributed to enhanced vascular nitric oxide synthesis. We investigated whether nitric oxide mediates the vasodilation that occurs in early human pregnancy.

Methods: Resting and stimulated forearm vascular resistance were measured (venous occlusion plethysmograph) in six women at 10 ± 3 weeks of uncomplicated pregnancy and in the same women 7 ± 5 weeks after elective termination of pregnancy. Forearm vascular resistance was also measured in six non-pregnant, healthy controls.

Results: Resting forearm vascular resistance was similar during pregnancy (33 ± 16 arbitrary units (AU)), after pregnancy (31 ± 10 AU) and in controls (41 ± 13 AU, P > 0.05). The decreases in forearm vascular resistance to intrabrachial infusions of acetylcholine (2 and 20 pg/min), serotonin (10 and 100 ng/min) and sodium nitroprusside (1 and 2.5 gg/min) were similar in all groups. The nitric oxide synthase inhibitor N^G-monomethyl-L-arginine (16 pmol/min) produced similar increases in vascular resistance in pregnant women (38 ± 17 AU), after pregnancy (36 ± 14 AU) and in control subjects (42 ± 8 AU, P = NS).

Conclusions: These results indicate that neither basal nor stimulated nitric oxide levels are altered in the forearm circulation during first trimester pregnancy.     

Nitric oxide does not modulate the hyperpolarization-activated current, I(f), in ventricular myocytes from spontaneously hypertensive rats

OBJECTIVE: : In sinoatrial (SA) node cells, nitric oxide (NO) exerts a dual effect on the hyperpolarization-activated current, I(f), i.e. in basal conditions NO enhances I(f) whereas in the presence of beta-adrenergic stimulation it decreases it. Recent studies have shown that I(f) is present in ventricular myocytes from hypertrophied or failing hearts where it may promote abnormal automaticity. Since these pathological conditions are associated with increased sympathetic tone and upregulation of myocardial NO production, we set out to investigate whether I(f) is similarly modulated by NO in hypertrophied ventricular myocytes. METHODS: Left ventricular myocytes were isolated from 18-20-month-old spontaneously hypertensive rats (SHRs). Membrane current was measured under whole-cell or amphotericin-perforated patch-clamp conditions, at 35 degrees C. RESULTS: Application of diethylamine-NO (DEA-NO, 1-100 microM) did not alter the amplitude or voltage dependence of activation of I(f) under basal conditions (half-activation voltage, V(h): control -82.9+/-2.6, DEA-NO -84.0+/-2.6 mV). Similarly, I(f) was not affected by the inhibition of endogenous NO production (L-NMMA, 500 microM) or guanylate cyclase (ODQ, 10 microM). Forskolin (10 microM) or isoprenaline (100 nM) elicited a positive shift in V(h) but subsequent application of DEA-NO did not further affect the properties of I(f). CONCLUSIONS: Our results show that, unlike in SA node cells, in SHR ventricular myocytes basal and adrenergically stimulated I(f) is not modulated by exogenous NO or by constitutive NO or cGMP production.     

Nitric oxide does not mediate flow induced endothelium dependent arterial dilatation in the cat.

OBJECTIVE: The aim was to determine whether the endothelium derived nitric oxide formed from L-arginine is the factor which mediates flow induced dilatation of conduit arteries. METHODS: Changes in diameter of feline femoral artery caused by blood flow rate increases, acetylcholine, and ATP were recorded during perfusion with blood in situ before and after the inhibition of endothelium derived nitric oxide synthesis by NG-nitro-L-arginine methyl ester and NG-monomethyl-L-arginine. Fourteen anaesthetised cats of either sex, weight 2.6-3.9 kg, were used for the studies. RESULTS: Intravenous administration of NG-nitro-L-arginine methyl ester and NG-monoethyl-L-arginine in doses 10 and 30 mg.kg-1 evoked a rise in mean systemic arterial pressure, constriction of the femoral artery, and considerable decrease in acetylcholine and ATP induced dilatation. However, it did not affect the dilator response induced by increased blood flow rate. CONCLUSIONS: Flow induced endothelium dependent arterial dilatation is not mediated by nitric oxide or, if nitric oxide is still released in response to flow rate increase, it has a source distinct from L-arginine.     

Nitric oxide synthase inhibition does not improve renal function in cirrhotic patients with ascites

OBJECTIVES: Based mainly on animal experiments, nitric oxide (NO) has been proposed to account for the peripheral arterial vasodilation and hyperdynamic circulation in liver cirrhosis. The aim of this study was to clarify whether a reduction of NO synthesis would ameliorate the circulatory and renal dysfunction in decompensated cirrhotic patients. METHODS: The effects of N(G)-monomethyl-L-arginine-acetate (L-NMMA), an NO synthesis inhibitor, were studied. After a 60-min basal period, a total of 10 patients received increasing doses of L-NMMA, five patients (Low) received 12.5, 25, and 50 microg/kg/min, and five patients (High) received 25, 50, and 100 microg/kg/min as a constant infusion during 3 h, followed by a postinfusion period. Five patients (Placebo) received saline infusions only. Glomerular filtration rate and renal plasma flow were measured by clearance techniques with (99m)Tc-diethylenetriamine-pentaacetate and (131)I-Hippuran. RESULTS: L-NMMA infusion resulted in an increased blood pressure, decreased heart rate, and dose-dependent suppression of renin of up to 42.1 +/- 7.1% (p < 0.01) and angiotensin II of up to 39.9 +/- 9.6%, (p < 0.01) levels. Sodium and water excretion were not improved, most likely because of a reduction in renal blood flow of up to 29.1 +/- 8.1% (p < 0.01). CONCLUSION: Despite a partial correction of the hyperdynamic circulation, inhibition of NO synthesis does not improve sodium and water excretion in decompensated cirrhosis, probably because of an accompanying decrease in renal plasma flow. Intrarenal NO synthesis may be important for maintaining intrarenal hemodynamics in decompensated cirrhotic patients.     

LPS binding protein does not participate in the pharmacokinetics of E5564

E5564, a lipid A analogue, is a potent antagonist of lipopolysaccharide (LPS). Clinically, E5564 was developed as a possible therapy for treatment of sepsis and septic shock. Surface plasmon resonance (SPR) analysis indicates that E5564 binds to LPS binding protein (LBP), in a manner similar to LPS. Gel-filtration radioactive chromatograms of [(14)C]-E5564 in plasma revealed that E5564 initially distributes to the lipoprotein fractions, separated from high-density lipoprotein (HDL); the bound fraction is then released and binds to HDL. Similar results were obtained by heparin-manganese precipitation. At doses of E5564 relevant to its clinical use (i.e. 6 microg/ml), antibodies against LBP did not influence either the distribution of E5564 to non-HDL lipoprotein fractions or the transfer of E5564 from non-HDLs to HDL. Under these conditions, transfer of E5564 to HDL occurs similarly in the plasma of LBP knockout (KO) mice as in the plasma from wild-type mice. In addition, plasma clearance of E5564 in LBP KO mice is similar to that of wildtype mice. Thus, LBP binds E5564 in a manner similar to LPS, but does not play a role in E5564 redistribution/binding to lipoprotein and plasma clearance.     

Nitric oxide does not significantly contribute to changes in pulse pressure amplification during light aerobic exercise

NO modulates resting blood pressure and wave reflection. The effect of NO on exercise central hemodynamics is unknown but has important implications relating to cardiovascular risk. The aim of this study was to determine the contribution of NO to pulse pressure (PP) amplification and wave reflection during exercise. Twelve healthy men aged 29+/-1 years (mean+/-SEM) undertook cycle exercise at 60% of their maximal heart rate. Noninvasive measures of central blood pressure, estimated aortic pulse wave velocity, and wave reflection (augmentation index) were obtained by pulse wave analysis during intravenous infusion of saline (control), N(G)-monomethyl-l-arginine (a NO-synthase inhibitor), or noradrenaline (control vasoconstrictor). PP amplification was defined as the ratio of peripheral to central PP. Cardiac output and stroke volume were determined by electric bioimpedance. Both N(G)-monomethyl-l-arginine and noradrenaline caused a significant increase in mean arterial pressure (P<0.01) and augmentation index (P<0.01), as well as reduced ratio of peripheral to central PP (P<0.05) at baseline. Exercise caused a significant increase in the ratio of peripheral to central PP (P<0.001), whereas augmentation index and estimated aortic pulse wave velocity declined (for both P<0.05) during all 3 of the infusion protocols. However, no significant differences were observed in augmentation index, ratio of peripheral to central PP, or estimated aortic pulse wave velocity between infusion procedures (P>0.50) during exercise. Also, heart rate, peripheral vascular resistance, and cardiac output did not differ during exercise between saline, N(G)-monomethyl-l-arginine, or noradrenaline. Although we cannot rule out other vasodilator mechanisms having adjusted for NO blockade, our results indicate that NO does not solely contribute to systemic arterial stiffness or altered blood pressure amplification during light exercise.     

Decrease in renal medullary endothelial nitric oxide synthase of fructose-fed,salt-sensitive hypertensive rats

We investigated the expression of endothelial NO synthase (eNOS) in the kidneys of fructose-fed insulin-resistant rats (FFR) with a low- or high-sodium diet. Male Sprague-Dawley rats were fed a control (C) or high-fructose (40% fructose; F) diet, with each coming in low-sodium (0.024% NaCl; LS-C or LS-F) or high-sodium (3% NaCl; HS-C or HS-F) varieties, for 2 weeks. Half of the FFR were orally administered pioglitazone (10 mg. kg(-1). day(-1)), an insulin-sensitizing agent (LS-FP or HS-FP). The systolic blood pressure was significantly higher in the HS-F rats than in the LS-F rats or the HS-C rats (HS-F rats, 129+/-4 mm Hg, versus LS-F rats, 115+/-3 mm Hg, P<0.05; or versus HS-C rats, 116+/-5 mm Hg, P<0.05), which indicated the salt dependence of hypertension in FFR. The protein expression of eNOS in the renal medulla of FFR was significantly lower than that in control rats during a high sodium load. The administration of pioglitazone prevented the hypertension (HS-F rats, 129+/-4 mm Hg, versus HS-FP rats, 113+/-3 mm Hg, P<0.05) and the reduction of medullary eNOS protein expression in HS-F rats. There was no significant difference in eNOS expression in the renal cortex or aorta between FFR and control rats, regardless of sodium load. These results suggest that the decrease in renal medullary NO production by eNOS during a high sodium load may play a role in fructose-fed, salt-sensitive hypertension.     

Aortic smooth muscle cell proliferation and endothelial nitric oxide synthase activity in fructose-fed rats

The aim of this study was to evaluate the proliferative behavior of vascular smooth muscle cells in primary culture (pC-SMC) and the endothelial nitric oxide synthase (eNOS) activity in the endothelial lining of the aorta of fructose-fed rats (FFR). This is an experimental model of syndrome X, a cluster of cardiovascular risk factors including hyperinsulinemia, insulin resistance, and hypertension that has been suggested to be of pathophysiologic importance for the development of atherosclerosis.Male Wistar rats were used: Control (n = 12) and FFR (n = 12). After receiving fructose in drinking water (10% w/v) during 8 weeks, biochemical parameters, systolic blood pressure (SBP) and relative heart weight (RHW) were determined. The proliferative effect of 10% fetal calf serum (FCS) was examined in aortic pC-SMC by [³H]thymidine incorporation and by cell counting. Ca²⁺/calmodulin-dependent NOS activity was estimated in aortic endothelial lining and in heart tissue homogenates by conversion of [³H]arginine into [³H]citrulline.Fructose-fed rats showed hyperinsulinemia (P = .0263), altered glucose tolerance test (P < .001), higher SBP (P < .0001), and RHW (P = .0145), compared to control rats. These animals also showed an increase of 10% FCS-induced [³H]thymidine incorporation (P < .0001) and cell number of aortic pC-SMC (P = .0049) and decreased eNOS activity in both aortic endothelium (P = .0147) and cardiac tissue (P < .0001).These data support the hypothesis that syndrome X is associated to changes in SMC proliferation and endothelial dysfunction, which could be involved in the onset or progression of the atherogenic process.     

Inhibition of neuronal nitric oxide synthase activity does not alter vasopressin secretion in septic rats

Background/Purpose

During the early phase of sepsis, hypotension is accompanied by increase of plasma vasopressin hormone (AVP) levels, which decline during the late phase. This hypotension is due in part to increase of nitric oxide (NO) synthesis by nitric oxide synthase (NOS) enzyme. Neuronal isoform of this enzyme (nNOS) is present in vasopressinergics neurons of hypothalamus, but its role in vasopressin secretion during sepsis is unknown.

Methods

We evaluated the role of nNOS in NO production and vasopressin secretion during sepsis. Wistar rats received 7-nitroindazole (50 mg/kg, i.p.), an inhibitor of nNOS activity, or vehicle and were submitted to septic stimulus by cecal ligation and puncture (CLP). At the time points 0, 4, 6, 18 and 24 h after sepsis induction the animals were decapitated and neurohypophysis and hypothalamus were removed for analysis of vasopressin content and NOS activity, respectively. Hematocrit, serum sodium, osmolality, proteins and plasmatic AVP were quantified.

Results

Mortality was not affected by 7-nitroindazole (7-NI). Sodium and plasma proteins levels decreased after CLP and the treatment anticipated the protein loss, and delayed serum sodium decrease. Septic animals treated with 7-NI showed decrease of osmolality 4 h after CLP. Nitric oxide synthase activity in hypothalamus increased at 4 and 24 h after CLP and was reduced with 7-NI. Neurohypophysis content of AVP diminished after CLP and 7-NI did not alter this parameter. Plasma AVP levels increased at 6 h and decreased 18 and 24 h after CLP. Treatment with 7-NI did not alter plasma vasopressin levels.

Conclusion

We concluded that nNOS does not have a substantial role in vasopressin secretion during experimental sepsis.

     

Nitric oxide contributes to the regulation of vasomotor tone but does not modulate O(2)-consumption in exercising swine

OBJECTIVE: The role of nitric oxide (NO) in the regulation of vasomotor tone and tissue O(2)-consumption is incompletely understood. We therefore determined the contribution of endogenous NO to regulation of systemic, pulmonary and coronary vasomotor tone and myocardial (MV(O(2))) and whole body (BV(O(2))) O(2)-consumption in exercising swine. METHODS AND RESULTS: Exercise (1-5 km/h) up to 85% of maximum heart rate in 11 swine produced a 4-fold increase in BV(O(2)), which was accommodated for by 2-fold increases in both cardiac output (CO) and body O(2)-extraction. The NO synthase inhibitor N(omega)-nitro-L-arginine (NLA, 20 mg/kg, i.v.) increased mean aortic pressure by 30 mmHg both at rest and during exercise, due to a decrease in systemic vascular conductance from 37+/-2 to 22+/-1 ml/min mmHg(-1) at rest and from 88+/-3 to 60+/-3 ml/min mmHg(-1) at 5 km/h (all P< or =0.05 versus control). NLA produced vasoconstriction at rest and at 5 km/h in virtually all regional beds but did not affect the exercise-induced redistribution of CO. NLA increased mean pulmonary artery pressure from 15+/-1 to 21+/-1 mmHg at rest and from 30+/-2 to 40+/-2 mmHg at 5 km/h, due to a decrease in pulmonary vascular conductance (all P< or =0.05). BV(O(2)) remained unchanged and consequently the decrease in CO resulted in a compensatory increase in O(2)-extraction. NLA in a dose of 40 mg/kg produced similar responses. NLA had no significant effect on myocardial O(2)-demand or MV(O(2)) either at rest or during exercise, but decreased coronary vascular conductance which resulted in a decrease in coronary venous PO(2) from 24.5+/-1.1 to 21.9+/-0.8 mmHg at rest and from 23.5+/-0.5 to 21.0+/-0.6 mmHg at 5 km/h (all P< or =0. 05). CONCLUSIONS: Endogenous NO dilates the systemic, pulmonary and coronary vascular bed, but does not modify MV(O(2)) or BV(O(2)) in swine at rest and during exercise.     

Nitric oxide production in arterial vessels of cirrhotic rats

Indirect evidence exists implicating vascular nitric oxide in the pathogenesis of arterial vasodilation in cirrhosis. In the current study, a coincubation assay to estimate the vascular nitric oxide production was developed and the nitric oxide production by arterial segments of cirrhotic and control rats was assessed. In the assay, measurement of reporter monolayer cell-associated cGMP levels allows the influence of nitric oxide released by arterial segments to be determined. RFL-6 cells served as reporter cells. Nitric oxide production was determined in thoracic aorta and mesenteric arteries of 22 control rats, 10 cirrhotic rats without ascites, and 12 cirrhotic rats with ascites. Basal and bradykinin-stimulated (10⁻⁶ mol/L) intracellular content of nitric oxide-dependent cGMP was significantly higher in RFL-6 cells coincubated with aortic segments of cirrhotic rats with (21.3 ± 3.6 pmol/10⁵ cells, P < .05 and 44.7 ± 7.0 pmol/10⁵cells, P < .025) and without ascites (15.3 ± 3.0 pmol/10⁵cells, P < .05 and 43.2 ± 7.6 pmol/10⁵cells, P < .05) than in those incubated with aortic segments of control rats (9.7 ±1.3 and 19.5 ± 2.5 pmol/10⁵cells). RFL-6 cells exposed to bradykinin-stimulated mesenteric arterial segments of cirrhotic rats also showed increased cGMP content (ascitic: 2.73 ± 0.31 pmol/10⁵cells, P < .005; nonascitic: 2.58 ± 0.51 pmol/10⁵cells, P < .025) compared with cells exposed to control mesenteric arterial segments (1.28 ± 0.15 pmol/10⁵cells). No differences between cirrhotic and control vessels were observed after endothelium denudation. These results indicate that basal and bradykinin-stimulated vascular nitric oxide production is higher in cirrhotic rats with and without ascites than in control rats in and that the endothelial lining is the site where vascular L-arginine nitric oxide pathway activation takes place in experimental cirrhosis.     

Mechanism of insulin resistance in fructose-fed rats

Previous results from our laboratory demonstrated that chronic administration of fructose to normal rats led to both hyperinsulinemia and in vivo insulin resistance. To localize the major tissue site of insulin resistance in fructose-fed animals, we compared glucose uptake by perfused hindlimb skeletal muscle and liver from rats fed either a 60% fructose diet or laboratory chow. Glucose uptake by perfused muscle from chow and fructose-fed rats was comparable at perfusate insulin levels of 0 μU/ml (15.2 versus 15.5 μl/min/g muscle), 100 μU/ml (18.3 versus 19.8), and >500 μU/ml (35.5 versus 33.4). In contrast, glucose outflow from livers of fructose-fed rats was significantly greater (p < .02) than chow-fed animals perfused in the absence of added insulin (52.1 versus 36.5 μmol/g). Furthermore, the ability of insulin to suppress glucose outflow was less in livers from fructose-fed rats at perfusate insulin levels of 165 μU/ml (13.2 versus 41.4% as well as at insulin concentration >900 μU/ml, (32.5% versus 62.2%). These findings suggest that the insulin resistance resulting from chronic fructose feeding is due to the diminished ability of insulin to suppress hepatic glucose output, and not to a decrease in insulin-stimulated glucose uptake by muscle.     

Hydralazine does not Ameliorate Nitric Oxide Resistance in Chronic Heart Failure

Purpose  

The A-HeFT trial demonstrated incremental survival with hydralazine/isosorbide dinitrate combination in African–American patients with chronic heart failure (CHF). It has been suggested that hydralazine might enhance nitric oxide (NO)—mediated effects of organic nitrates by decreasing superoxide (O₂⁻) formation, one of the factors inducing NO resistance. We evaluated whether hydralazine therapy potentiates nitrate-induced vasodilation and inhibition of platelet aggregation by ameliorating NO resistance.     

Nitric oxide is involved in the insulin release in rats byl-arginine

The insulinogenic effect ofl-arginine has been demonstrated bothin vivo andin vitro, but the mechanism by which this amino acid stimulates the pancreatic B-cells to release insulin is not entirely clear. Recently it was shown thatl-arginine-derived nitric oxide may mediatel-arginine-induced insulin release, and data were also provided to suggest that nitric oxide (NO) has no part in this process. To further investigate whether NO is involved in the release of insulin induced byl-arginine, we infused different doses ofl- andd-arginine in rats. L-Arginine (25 and 100 mg/kg/minute) elicited dose-dependent increases of the plasma insulin levels by up to 18.65±2.13 and 48.6±6.6 U/L, respectively, and increased the plasma glucose levels by up to 1.18±0.13 and 1.43±0.1 mmol/L, respectively. D-Arginine (25 and 100 mg/kg/minute) also elicited dose-dependent increases of the plasma insulin levels by up to 9.08±1.23 and 23.33±2.33 U/L, and increased the plasma glucose levels by up to 0.32±0.09 and 0.46±0.08 mmol/L. Thus, the increases in plasma insulin and glucose levels were significantly smaller during infusion ofd-arginine. We conclude that the plasma insulin response to i.v. infusion ofl-arginine is at least partly mediated by augmented NO synthesis by the pancreatic islets, althoughl-arginine-derived NO is not an obligatory stimulus for insulin release.     

Nitric oxide mediates sexual behavior in female rats.

Nitric oxide (NO), an active free radical formed during the conversion of arginine to citrulline by the enzyme NO synthase (NOS), mediates vasorelaxation, cytotoxicity, and neurotransmission. Neurons containing NOS (NOergic) are located in the hypothalamus. These NOergic neurons control the release of several hypothalamic peptides. Release of NO from these NOergic neurons stimulates pulsatile release of luteinizing hormone-releasing hormone (LHRH) in vivo and LHRH release in vitro. LHRH not only induces LH release, which induces ovulation, but also facilitates female sexual behavior. Sexual behavior can be induced reliably in estrogen-primed ovariectomized female rats by progesterone (P). This behavior consists of proceptive behavior to attract the male and the assumption of a clear characteristic posture, lordosis, when mounted by the male. To ascertain the role of NO in the control of sexual behavior in female rats, an inhibitor of NOS, NG-monomethyl-L-arginine was microinjected into the third cerebral ventricle (3V) of conscious, ovariectomized, estrogen-primed rats with indwelling cannulae. NG-Monomethyl-L-arginine (10-1000 micrograms) prevented P-facilitated lordosis when administered intracerebroventricularly into the 3V, 20 min prior to the 3V injection of P. NG-Monomethyl-D-arginine, which does not inhibit NOS, did not inhibit lordosis under the same experimental conditions. Microinjection into the 3V of sodium nitroprusside (SNP), which spontaneously releases NO, facilitated lordosis in estrogen-primed rats in the absence of P. The facilitation of lordosis induced by either P or SNP was prevented by intracerebroventricular injection of hemoglobin, which binds NO. Lordosis facilitated by P or SNP was blocked by injection of LHRH antiserum into the 3V. The results are interpreted to mean that the P-facilitated lordosis response is mediated by LHRH release. Furthermore, since NO release from SNP also facilitates lordosis in the absence of P and this response could be blocked by LHRH antiserum, we conclude that P brings about the release of NO, which stimulates LHRH release that facilitates lordosis. Thus, the results indicate that NO induces LHRH release and that LHRH then plays a crucial role in mediation of sexual behavior in the female rats.     

Nitric oxide synthase activity in hyperthyroid and hypothyroid rats

OBJECTIVE: Thyroid disorders are accompanied by important changes in haemodynamic and cardiac functions and renal sodium handling. Since nitric oxide (NO) plays a crucial role in regulating vascular tone and renal sodium excretion, the present paper was designed to determine whether changes in the activity of NO synthase (NOS) participate in the cardiovascular and renal manifestations of thyroid disorders. METHODS: We measured NOS activity in the heart (left and right ventricles), vessels (aorta and cava) and kidney (cortex and medulla) of euthyroid, hyperthyroid and hypothyroid rats after 6 weeks of treatment. NOS activity was determined by measuring the conversion of L-[(3)H]-arginine to L-[(3)H]-citruline. RESULTS: NOS activity was higher in all tissues from hyperthyroid rats when compared with controls, except in the right ventricle. In the hypothyroid group, NOS activity showed a more heterogeneous pattern, with significant increases in both ventricles but significant reduction in the aorta, while in the vena cava, renal cortex and medulla the enzyme activity also tended to be higher, but significance was not reached. CONCLUSIONS: These data indicated that NOS activity was upregulated in tissues primarily related to blood pressure control in hyperthyroid rats, suggesting that an increased NO production may contribute to the hyperdynamic circulation in hyperthyroidism and may have a protective homeostatic effect in the target organs of the hypertension that accompanies this endocrine disease. The aortic and renal findings in hypothyroid rats suggested a possible role for NOS in the increased peripheral resistance and the normal pressure-diuresis-natriuresis response of these hypotensive animals, although hypothyroidism produced a heterogeneous tissue response in NOS activity.     

一氧化氮对哮喘大鼠基质金属蛋白酶的表达调控

目的　观察一氧化氮 (NO)对哮喘大鼠基质金属蛋白酶 (MMP)及金属蛋白酶组织抑制物表达的影响 ,探讨其在哮喘气道结构重建中的作用。方法　 30只雄性Wistar大鼠随机分为对照组、哮喘组和左旋精氨酸组 (L Arg组 ) ,每组 1 0只。肺组织作病理切片并HE染色 ,通过病理图像分析系统测定支气管基底膜周径 (Pbm)、总管壁面积 (WAt)、内壁面积 (WAi) ,平滑肌面积 (WAm)等形态学参数。用NO与一氧化氮合酶 (NOS)试剂盒测定肺组织中亚硝酸盐 /硝酸盐 (NO- 2 /NO- 3)水平与NOS活性。半定量逆转录聚合酶链反应技术 (RT PCR)分析肺组织中MMP 2与TIMP 1mRNA的表达。结果(1 )WAt/Pbm、WAi/Pbm及WAm/Pbm哮喘组 [分别为 (2 5 3± 2 1 ) μm2 / μm、(2 0 4± 2 3) μm2 / μm、(4 2±2 0 ) μm2 / μm]和L Arg组 [分别为 (35 1± 2 6) μm2 / μm、(2 5 3± 2 0 ) μm2 / μm、(8 7± 1 5) μm2 / μm]与对照组 [分别为 (2 0 8± 1 3) μm2 / μm、(1 5 3± 2 1 ) μm2 / μm、(3 1± 1 1 ) μm2 / μm]比较 ,差异有显著性(P <0 0 1 ) ;L Arg组与哮喘组比较差异亦有显著性 (P <0 0 5)。 (2 )肺组织中NO- 2 /NO- 3水平哮喘组[(7 2± 2 1 )nmol/mg]和L Arg组 [(1 1 8± 1 7)nmol/mg]与对照组 [(3 1± 1 2 )n