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Query: UMLS:C0406810 (
NAME
)
13,345
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
We investigated the mechanisms of renal vascular wall thickening in a rat model of N-nitro L-arginine methyl ester (L-
NAME
)-induced hypertension. To separate the effects of L-
NAME
-induced hypertension from other effects of nitric oxide (NO) inhibition, we created two models of L-
NAME
-induced hypertension: both had the same blood pressure level but NO inhibition was moderate in one group (group M) and severe in the other (group S). Urinary excretion of nitrates and nitrites was lower in group S than in group M. Wall thickening and lipid deposition in renal vessels were significantly greater in group S than in groups M. Simple and multiple regression analyses indicated that renal vascular wall thickening was more strongly correlated with lipid deposition than with blood pressure. The number of vessels positive for staining with Sudan black B was negatively correlated with urinary NO excretion. Expression of fibronectin and
transforming growth factor-beta
was greater in the Sudan black B-positive than in the Sudan black B-negative vessels, suggesting that extracellular matrix production was increased in vessels with lipid deposition. Lipid deposition and increased production of extracellular matrix may contribute to renal vascular wall thickening in L-
NAME
-induced hypertension. Some mechanisms independent of hypertension play important roles in vascular wall thickening induced by NO inhibition.
...
PMID:The contribution of nitric oxide to renal vascular wall thickening in rats with L-NAME-induced hypertension. 987 Jun 89
Vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and
transforming growth factor-beta
(1) (TGF-beta(1)) mRNA increase in rat skeletal muscle in response to a single acute exercise bout. Nitric oxide (NO) is released locally by muscle vascular endothelium and muscle fibers during exercise, contributes to the blood flow response to exercise, and regulates mitochondrial respiration. We hypothesized that a reduction in NO production, via NO synthase inhibition, would demonstrate a link between NO and the VEGF, bFGF, and TGF-beta(1) gene responses to exercise. To investigate this hypothesis, 9-wk-old female Wistar rats were divided into eight treatment groups (n = 6 each): 1) saline + rest, 2) saline + exercise, 3) 30 mg/kg N(omega)-nitro-L-arginine methyl ester (L-
NAME
, a known NOS inhibitor) + rest, 4) 30 mg/kg L-
NAME
+ exercise, 5) 300 mg/kg L-
NAME
+ rest, 6) 300 mg/kg L-
NAME
+ exercise, 7) 300 mg/kg N(omega)-nitro-D-arginine methyl ester (D-
NAME
, inactive enantiomer of L-
NAME
) + rest, and 8) 300 mg/kg D-
NAME
+ exercise. Exercise consisted of 1 h of running at 20 m/min on a 10 degrees incline. VEGF, TGF-beta(1), and bFGF mRNA from left gastrocnemius were analyzed by quantitative Northern blot. Submaximal exercise for 1 h increased VEGF mRNA 4.2-fold and TGF-beta(1) mRNA 1.5-fold in untreated rats but did not increase bFGF mRNA. The exercise-induced increase in VEGF mRNA was attenuated approximately 50% by 30 and 300 mg/kg L-
NAME
; the TGF-beta(1) mRNA increase was unaffected by 300 mg/kg L-
NAME
. In addition, 300 mg/kg D-
NAME
had no effect on the exercise-induced increase in VEGF mRNA. Administration of 300 mg/kg L-
NAME
had no effect on bFGF mRNA. These findings suggest that NO is important in the regulation of the VEGF gene response to exercise through increases in VEGF transcription or by increases in the VEGF mRNA half-life.
...
PMID:Nitric oxide synthase inhibition attenuates the skeletal muscle VEGF mRNA response to exercise. 1074 7
Long-term blockade of nitric oxide synthesis with N(omega)-nitro-L-arginine methyl ester (L-
NAME
) induces cardiac perivascular fibrosis in rats. Its relationship to expression of angiogenic growth factors and capillary network remodeling is not understood. This study was designed to determine whether capillary proliferation and angiogenic growth factor regulation occur in response to L-
NAME
. Three groups of rats were studied: C, control; L1, L-
NAME
13 mg/kg/day; L2, 130 mg/kg/day. One and eight weeks later the hearts were removed and subjected to morphometric analysis and analysis of gene expressions of molecules related to angiogenesis. Arterial hypertension was observed within 8 weeks in the L1 and L2 groups compared with control. After 1 week immunohistochemical assays demonstrated basic fibroblast growth factor (bFGF) in the arteriolar media. Northern blot analysis revealed increase in bFGF and
transforming growth factor-beta
(
TGF-beta
) mRNA during this period. At 8 weeks arteriolar medial thickening and perivascular fibrosis were seen microscopically in the L1 and L2 groups, which were accompanied by only a modest remodeling of capillary network due to increase in venular or intermediate capillary portions. Concomitantly immunoreactivity for vascular endothelial growth factor (VEGF) and
TGF-beta
were detected in perivascular area. These results suggest that (1) blockade of NO synthesis induces expression of angiogenic growth factors as well as vessel wall remodeling, and (2)
TGF-beta
may counteract angiogenic growth factors and limit subsequent alterations in capillary network remodeling.
...
PMID:Long-term blockade of nitric oxide synthesis in rats modulates coronary capillary network remodeling. 1451 31
This study examined the expression of inducible nitric oxide synthase (iNOS) and
transforming growth factor-beta
(
TGF-beta
) in macrophage infiltrates within crush-injured digital flexor tendon and synovium of control rats and rats treated with N(G)-nitro-1-arginine methyl ester (L-
NAME
) (5 mg/kg). Release of
TGF-beta
from organ cultures of tendon, muscle, and synovium, and the effects of L-
NAME
treatment (in vitro and in vivo), on adhesion of peritoneal macrophages to epitenon monolayers were also investigated. The results showed that during normal tendon healing the levels of
TGF-beta
are high at first and gradually decrease after 3 weeks of injury to slightly above control uninjured levels. However, when L-
NAME
was administered at the time of injury, the macrophage infiltrates were expressing high levels of
TGF-beta
even at 5 weeks after the injury, with no evidence of reduction. In the standard injury, iNOS activity was greatest at the acute phase of the inflammatory response and then gradually returned to normal. Treatment with L-
NAME
, however, resulted in inhibition of iNOS activity at 3 days and a reduction in the activity at the later time points examined after injury. We also found greatly increased levels of adhesion of peritoneal macrophages from L-
NAME
-treated rats to epitenon monolayers in vitro, which reflect a chronic imbalance in expression of
TGF-beta
, which is overexpressed, and nitric oxide, which is underexpressed. The results of the current study show that formation of nitric oxide is an important event in the course of tendon healing since its inhibition results in chronic inflammation and fibrosis due to an imbalance in
TGF-beta
expression in vivo.
...
PMID:Expression of nitric oxide synthase and transforming growth factor-beta in crush-injured tendon and synovium. 1577 44
The prevalence of atrial fibrillation (AF) increases in patients with hypertension. Angiotensin II is involved in structural atrial remodeling, which contributes to the onset and maintenance of AF in paced animal models. We investigated the role of angiotensin II in atrial structural remodeling in rats with hypertension. Ten-week-old male Wistar-Kyoto rats were randomly divided into 4 groups: a control group (no treatment), an Nomega-nitro-L-arginine methyl ester (L-
NAME
) group (administered L-
NAME
, an inhibitor of nitric oxide synthase, 1 g/l in drinking water), an L-NAME+candesartan group (L-
NAME
plus candesartan-an angiotensin II receptor blocker (ARB)-at 0.1 mg/kg/day), and an L-
NAME
+ hydralazine group (L-
NAME
plus hydralazine at 120 mg/l in drinking water). Eight weeks after treatment, the L-
NAME
group showed significantly higher systolic blood pressure than the control group (197 +/- 12 vs.138 +/- 5 mmHg, p < 0.05). Candesartan or hydralazine with L-
NAME
reduced systolic blood pressure to baseline. Chronic inhibition of NO synthesis increased the extent of fibrosis and
transforming growth factor-beta
expression in atrial tissue, and both of these effects were prevented by candesartan, but not by hydralazine. Cardiac hypertrophy and dysfunction were induced in the L-
NAME
group, and these effects were also prevented by candesartan, but not by hydralazine. In contrast, the decrease in thrombomodulin expression in the atrial endocardium in hypertensive rats was restored by candesartan and hydralazine. The ARB prevented atrial structural remodeling, a possible contributing factor for the development of AF, in the hearts of rats with hypertension induced by long-term inhibition of NO synthesis.
...
PMID:Angiotensin II type 1 receptor blocker prevents atrial structural remodeling in rats with hypertension induced by chronic nitric oxide inhibition. 1677 35
To investigate whether the receptor blockades of angiotensin II type 1 and aldosterone receptors can prevent renal tissue injury in relation to the renal tissue mRNA levels of peroxisome proliferation-activated receptors-gamma (PPAR-gamma) and
transforming growth factor-beta
(1) (TGF-beta(1)) in spontaneously hypertensive rats (SHR) given N(G)-nitro-L-arginine methyl ester (L-
NAME
), which is considered a model of malignant hypertension. This study was performed in 5 groups of 17-week-old male SHR treated for 3 weeks as follows: group 1, control; group 2, L-
NAME
(50 mg/L in drinking); group 3, L-
NAME
plus aldosterone antagonist, spironolactone (SPRL, 100 mg/kg/day); group 4, L-
NAME
plus angiotensin II type 1 receptor blocker, telmisartan (TELM, 3 mg/kg/day); group 5, L-
NAME
plus combination therapy (COMB) with low-dose TELM (1 mg/kg/day) and SPRL (100 mg/kg/day). Urinary protein excretion and the glomerular injury score were significantly reduced in the SPRL, TELM, and COMB groups as compared with the L-
NAME
group, while significant blood pressure reduction was observed only in the TELM group. In the TELM and COMB groups, the perivascular cell infiltration and fibrosis area were significantly reduced together with the PPAR-gamma mRNA increase and TGF- beta(1) mRNA decrease. The urinary excretion of nitric oxides was significantly recovered and the wall to lumen ratio of the interlobular artery was significantly reduced only in the COMB group compared with the L-
NAME
group. Combined administration of 1 mg/kg/day telmisartan and 100 mg/kg/day spironolactone is thought to be effective in alleviating hypertensive renal injuries independently of blood pressure changes. The anti-inflammatory and antifibrotic effects due to PPAR-gamma activation and TGF-beta(1) inhibition may participate in the renoprotection of this combination therapy.
...
PMID:Combination therapy with telmisartan and spironolactone alleviates L-NAME exacerbated nephrosclerosis with an increase in PPAR-gamma and decrease in TGF-beta(1). 1799 73
