Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The spontaneously hypertensive fawn-hooded rat (FHH) develops accelerated albuminuria and focal glomerular sclerosis (FGS), leading to ESRD and shortening of lifespan. The FHH is characterized by moderate systemic hypertension, a relatively low afferent to efferent arteriolar resistance ratio, and glomerular hypertension. The FHH study presented here was designed to examine the efficacy of early-onset, late-onset, or early-temporary angiotensin I-converting enzyme inhibition (ACE-i) in ameliorating long-term hypertension and FGS, and improving survival, as well as to relate its protective efficacy to preexistent FGS and to reduction of glomerular pressure (PGC) Untreated rats developed hypertension and high PGC, and all (N = 22) except one died of ESRD within the 72-wk follow-up period. Early-onset (at 7 wk of age) ACE-i prevented development of systemic and glomerular hypertension, and it largely prevented proteinuria and FGS; all rats survived throughout the follow-up period. Rats treated with late-onset (22 wk) ACE-i were hypertensive and proteinuric at the start of ACE-i, and they showed beginning FGS. ACE-i corrected the hypertension, albuminuria, and PGC but could not fully prevent some hypertension, albuminuria, and FGS at the later stage. Early-temporary (7 to 22 wk) ACE-i adequately controlled blood pressure and development of FGS during therapy, but after withdrawal of ACE-i, systemic and glomerular hypertension developed as in untreated animals. This regimen postponed but did not control FGS development and early mortality. The results of this study indicate that: (1) early-onset ACE-i very effectively protects against development of renal damage in the FHH; (2) this protection is associated with normalization of the elevated glomerular capillary pressure; (3) ACE-i cannot completely prevent further development of previously established FGS, despite lowering glomerular capillary pressure; (4) early-temporary ACE-i has no long-term controlling effect on arterial and glomerular pressure, and it cannot control development of FGS.
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PMID:Angiotensin-converting enzyme inhibition in the prevention and treatment of chronic renal damage in the hypertensive fawn-hooded rat. 904 44

The hypertensive fawn-hooded (FHH) rat develops progressive albuminuria (UalbV) and focal glomerulosclerosis (FGS). Early-onset angiotensin-converting enzyme inhibition (ACE-i) completely prevented the development of hypertension, UalbV, and FGS. ACE-i was still effective when the start of treatment was delayed, albeit less than early-onset treatment. In this study, we examined whether more advanced renal damage reduces the efficacy of ACE-i, and, if so, which factors dampen the efficacy. ACE-i was started in 36-week-old FHH rats, and follow-up consisted of regular assessment of systolic blood pressure (SBP) and UalbV. Untreated rats, matched for age, SBP, and UalbV, served as controls. In separate groups, untreated or treated with ACE-i from either week 7 or week 36, glomerular hemodynamics and FGS were determined at week 40. ACE-i normalized SBP and markedly reduced UalbV. The Initial UalbV response to ACE-i was inversely correlated with pretreatment UalbV, but despite control of SBP, UalbV rose again. Eventually, rats died of terminal renal failure. Life expectancy was significantly increased in treated rats. In both untreated and treated rats, there was a significant inverse correlation between baseline UalbV and survival time. However, the gain in survival time decreased when pretreatment UalbV was higher. Late-onset ACE-i reduced glomerular capillary pressure to the same extent as early-onset ACE-i. There was a significant linear correlation between FGS and UalbV. We conclude that in FHH rats with advanced renal damage, ACE-i slows down the progression to terminal renal failure. The outcome is an increased survival time that is inversely correlated with baseline UalbV.
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PMID:ACE inhibition delays development of terminal renal failure in the presence of severe albuminuria. 1067 17

Emerging evidence suggests that physical activity and sedentary behavior [reflected in physical inactivity (PI)], might be two different phenotypes that may have distinct underlying physiological mechanisms. The purpose of this review is to summarize the existing literature on the genetic determinants of PA and PI phenotypes in humans, considering them as distinct behaviors. Completed in January 2011, this review includes family studies, twin studies, association studies, genome-wide linkage studies and genome-wide association scan (GWAs) reporting different physical activity/inactivity-related phenotypes. In regards to PA, familial aggregation studies resulted in heritability estimates ranging from 0 to 60 %, and twin studies yielded heritability estimates (a(2)) and shared environment (c(2)) scores for PA phenotypes ranging from 0.00 to 0.85 and 0.00 to 0.84, respectively. Unique environmental (e(2)) results are well dispersed from 0.12 to 0.72. Suggestive linkages were found with markers nearby different activity-related genes: EDNRB, MC4R, UCP1, FABP2, CASR, SLC9A9. Significant associations with PA phenotypes were found for Ace, Gln223ARrg, MC4R and DRD2 genes. We found one GWAs that reported novel SNPs in the PAPSS2 gene on chromosome 10q23.2 and in two intergenic regions on chromosomes 2q33.1 and 18p11.32. Heritability estimates for PI ranged from 25 to 60 % and linkage studies recorded higher LOD scores for PI versus PA. The ACE genotype was strongly associated with PI. There are potentially different genetic influences on PA versus PI phenotypes. Future studies should focus on the different genetic influences on PA and PI to improve our understanding of underlying determinants of these behaviors.
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PMID:Genetics of physical activity and physical inactivity in humans. 2242 82