Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Renal prostaglandins (PGs) help maintain renal blood flow and glomerular filtration rate when the kidney is exposed to a vasoconstrictor stress. In addition, they aid pressure natriuresis and blunt the antidiuretic effect of vasopressin. Angiotensin-converting enzyme (ACE) inhibitors could decrease renal PG synthesis by reducing angiotensin II (Ang II) formation or increase it by preventing kinin inactivation. Additionally, they could affect PG synthesis or catabolism directly. The effects of ACE inhibitors on blood pressure and renal hemodynamics appear to be largely independent of changes in renal PG synthesis. Similarly, there is no evidence that pressure natriuresis is modified by ACE inhibitors. A kinin induced increase in collecting duct PG synthesis may account for the water diuresis seen clinically with ACE inhibitors. A possible beneficial interaction between thromboxane synthesis inhibitors and ACE inhibitors may exist. Thromboxane synthetase inhibitors can reduce renal vascular resistance by redirecting PG endoperoxide synthesis toward prostacyclin. This effect may be offset by a prostaglandin-induced increase in renin release and Ang II formation. ACE inhibitors, by preventing Ang II synthesis, may increase the vasodilation due to thromboxane synthesis inhibition.
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PMID:Renal prostaglandin synthesis and angiotensin-converting enzyme inhibition. 138 64

The activity of angiotensin I-converting enzyme (ACE) was determined in tubular fluid collected from several portions of the rat nephron and urine and in total and efferent arteriolar blood using hippuryl-L-His-Leu as substrate. ACE activity decreased 30% from the pre- to the postglomerular arterioles (P < 0.001), suggesting a role of the glomerulus in ACE clearance. The enzyme activity was found to be present throughout the rat nephron. However, the highest activities were found in the proximal tubule and urine (0.692 +/- 0.007 and 1.05 +/- 0.015 pmol x microl(-1) x min(-1), respectively). Compared with other segments, ACE activity decreased from the initial portion of the proximal tubule to the distal nephron and increased again in the urine. Along the proximal tubule, ACE was secreted and degraded and/or reabsorbed and then secreted again into the collecting duct; no ACE activity was found in the late distal tubule, but a high level was detected in the urine, indicating a potential physiological role in the inactivation of the kinins formed by kallikrein beyond the connecting tubules. Moreover, the possible role of mesangial cells (MC) in the decrease of intraglomerular ACE was also evaluated. The analysis of ACE gene showed that MC in culture are able to express ACE mRNA. Moreover, ACE is produced as an ectoenzyme and as a secreted form of the enzyme, indicating a potential effect of local angiotensin II production on MC function.
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PMID:Angiotensin I-converting enzyme activity in tubular fluid along the rat nephron. 908 85

Obstructive uropathy impairs nephron growth and function and is a major cause of end-stage renal disease in both adults and children. The major focus of this review article is to examine the evidence implicating a role for the kallikrein-kinin system in the pathophysiology of obstructive uropathy. Recent in vivo studies using specific kinin receptor antagonists and transgenic animals overexpressing or lacking various components of the kallikrein-kinin system have documented that kinins are involved in the regulation of renal function and blood pressure. Multiple roles have been proposed for kinins in obstructive uropathy. Renal kallikrein gene expression is suppressed in the kidney with chronic (>7 days) complete ureteral obstruction. In contrast, ureteral obstruction stimulates renin expression, creating a state of intrarenal angiotensin excess and kinin deficiency, which plays an important role in mediating the increased renal vascular resistance and decreased renal blood flow in the obstructed kidney. In addition to their hemodynamic effects, kallikrein and kinins influence tubular functions. For example, kallikrein influences urinary acidification in the distal nephron, suggesting that dysregulation of kallikrein expression may contribute to the acidification defect in the obstructed kidney. Also, kinins exert direct diuretic and natriuretic effects in the collecting duct and may be important in mediating the post-obstructive diuresis after the relief of urinary obstruction. The kinin substrate, kininogen, is a potent inhibitor of lysosomal cysteine proteases. Unlike kallikrein, kininogen synthesis is upregulated in the kidneys and liver of animals with urinary obstruction. By neutralizing cysteine proteases, kininogen may protect the tubular epithelium of obstructed nephrons from excessive apoptosis. The beneficial actions of kinins and kininogens on renal hemodynamics, tubular function, and cell survival suggest that strategies aimed at increasing intrarenal kinins, eg, ACE-kininase II inhibitors and kallikrein gene therapy, may represent a useful adjunct in the medical treatment of obstructive uropathy.
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PMID:The kininogen gene family in obstructive uropathy. 981 54

The intrarenal renin-angiotensin system (RAS) has an important role in generating and maintaining hypertension in two-kidney, one-clip (2K1C) rats. This study evaluated how various intrarenal RAS components contributed to hypertension not only in the maintenance period (5w; 5 wk after operation) but also earlier (2w; 2 wk after operation). We inserted a 2.5-mm clip into the left renal artery of Sprague-Dawley rats and euthanized them at 2w and 5w following the operation. Systolic blood pressure increased within 1 wk after the operation, and left ventricular hypertrophy occurred in 2K1C rats. At 2w, juxtaglomerular apparatus (JGA) and collecting duct (CD) renin increased in clipped kidney (CK) of 2K1C rats. The tubular angiotensin I-converting enzyme (ACE) was not changed, but peritubular ACE2 decreased in nonclipped kidney (NCK) and CK of 2K1C rats. At 5w, ACE and CD renin were enhanced, and ACE2 was still lessened in both kidneys of 2K1C rats. However, plasma renin activity (PRA) was not different from that in sham rats. In proximal tubules of CK, the ANG II type 1 receptor (AT1R) was not suppressed, but the Mas receptor (MasR) was reduced; thus the AT1R/MasR ratio was elevated. Although hypoxic change in CK could not be excluded, the JGA renin of CK and CD renin in both kidneys was highly expressed independent of time. Peritubular ACE2 changed in the earlier period, and uninhibited AT1R in proximal tubules of CK was presented in the maintenance period. In 2K1C rats, attenuated ACE2 seems to contribute to initiating hypertension while upregulated ACE in combination with unsuppressed AT1R may have a key role in maintaining hypertension.
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PMID:Sequential activation of the intrarenal renin-angiotensin system in the progression of hypertensive nephropathy in Goldblatt rats. 2682 79