Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0403608 (ureter)
 9,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The contribution of sympathetic nerves to the hemodynamic effects of unilateral ureteral obstruction (UUO) was investigated in the neonatal guinea pig. The left ureter was partially constricted (or sham-operated) at birth, and sympathetic innervation was inhibited by guanethidine and compared with saline vehicle-treated animals. At 15-20 days of age, blood pressure, cardiac output, total vascular resistance (TVR), renal blood flow, and renal vascular resistance (RVR) were determined before and after infusion of enalapril. UUO reduced cardiac output, increased TVR, and increased RVR of the ipsilateral kidney, whereas guanethidine treatment had no additional effects. Enalapril decreased RVR only in obstructed kidneys and not in intact opposite kidneys of animals with UUO. This was not affected by guanethidine administration. In contrast, enalapril decreased RVR only in guanethidine-treated (but not saline-treated) sham-operated guinea pigs. Therefore, UUO increases angiotensin-dependent vascular tone of the ipsilateral kidney independent of renal innervation. However, UUO decreases angiotensin-mediated vascular tone of the contralateral kidney, an effect unmasked by sympathectomy.
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PMID:Ureteral obstruction in the neonatal guinea pig: interaction of sympathetic nerves and angiotensin. 757 6

Angiotensin-converting enzyme (ACE) inhibitors have been shown to minimize fibrosis of the kidney tubulointerstitium in several diseases. In addition to lowering angiotensin II levels, ACE inhibitors can increase kinin levels and subsequently increase nitric oxide formation. To determine whether nitric oxide generation is a component of the beneficial effect of ACE inhibitors on renal fibrosis, enalapril, enalapril plus NG-nitro-L-arginine methyl ester (L-NAME) or L-arginine was administered to rats that had undergone unilateral ureteral obstruction (UUO). Ureteral obstruction caused significant increases in interstitial volume, monocyte macrophage infiltration, interstitial collagen IV and alpha-smooth muscle actin expression, transforming growth factor-beta 1 mRNA, collagen IV mRNA, and tissue inhibitor of metalloproteinase-1 mRNA. Enalapril treatment significantly blunted the increase in all parameters during UUO. Cotreatment of the animals with enalapril and L-NAME reversed the beneficial effect of enalapril in the obstructed kidney for all parameters. Treatment of animals with UUO with L-arginine significantly blunted the increase in all parameters except for transforming growth factor-beta 1 mRNA expression. In the enalapril- plus-L-NAME-treated animals, there were modest but significant increases in monocyte/macrophage infiltration of the interstitium and glomerulus, and collagen IV and alpha-smooth muscle actin expression in the interstitium of the contralateral unobstructed kidney. The urine nitrite concentration was significantly increased by either enalapril or L-arginine treatment, whereas L-NAME significantly reduced urine nitrite concentration. These results suggest that treatment modalities that increase nitric oxide formation have a beneficial effect on the progression of cellular and molecular parameters of tubulointerstitial fibrosis caused by obstruction of the ureter.
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PMID:Nitric oxide generation ameliorates the tubulointerstitial fibrosis of obstructive nephropathy. 891 81

Unilateral ureteral obstruction (UUO) is a well-established model for the study of interstitial fibrosis in the kidney. It has been shown that the renin-angiotensin system plays a central role in the progression of interstitial fibrosis. Recent studies indicate that endothelin, a powerful vasoconstrictive peptide, may play an important role in some types of renal disease. To investigate the effects of angiotensin II on endothelin and its receptors in the kidney, mice were subjected to UUO and treated with or without enalapril, an orally active angiotensin-converting enzyme inhibitor, in their drinking water (100 mg/l). The animals were killed 5 days later. Using RT coupled with PCR, we measured the levels of endothelin-1, endothelin A, and endothelin B (ET(B)) along with transforming growth factor-beta, TNF-alpha, and collagen type IV mRNA expression in the kidney with UUO and the contralateral kidney along with interstitial expansion in the kidney cortex by a standard point counting method. We found that enalapril administration ameliorated the increased expression of ET-1 mRNA in the obstructed kidney by 44% (P < 0.02). Although the level of endothelin A mRNA expression was significantly increased in the obstructed kidney, it was not affected by enalapril. We found that enalapril treatment increased ET(B) mRNA expression by 115% (P < 0.05) and protein expression (measured by Western blot) in the kidney with an obstructed ureter. Enalapril treatment alone inhibited the expansion of interstitial volume due to UUO by 52%. Cotreatment with enalapril and the ET(B) receptor antagonist BQ-788 inhibited the expression of interstitial volume by only 19%. This study confirms that enalapril inhibits the interstitial fibrosis in UUO kidneys. It also suggests a beneficial and unforeseen effect of enalapril on the obstructed kidney by potentially stimulating the production of nitric oxide through an increased expression of the ET(B) receptor.
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PMID:ACE inhibition increases expression of the ETB receptor in kidneys of mice with unilateral obstruction. 1247 37