Sustained Tubulo-interstitial Protection in SHRs by Transient Losartan Treatment: An Effect of Decelerated Aging?

Abstract

Transient losartan treatment reduces cell-turnover not only acutely but also for a prolonged period after drug withdrawal. This results in the long-term in reduced aging and attenuated tubulo-interstitial damage, suggesting there exists a modulating effect of angiotensin II (ANGII)-antagonism on long-term cell turnover.

Effect of uric acid on hypertension progression in spontaneously hypertensive rats

“…UA inhibits the proliferation of renal proximal tubule cells, with no cytotoxic effects (Han et al 2007). The possibility exists that UA impedes the progression of hypertension in SHR by decreasing the activated proliferation (Baumann et al 2008), and consequently, trans-differentiation (Zeisberg 2001) and fibrotic process (Camp et al 2003) associated with tubule cells in this strain, factors that contribute to hypertensive remodeling.…”

Is cellular senescence important in pediatric kidney disease?

“…In addition to cardiovascular risk factors previously discussed [45,46], diabetes and oxidative stress have been shown to induce premature senescence in endothelial and smooth-muscle cells in several animal models. Young diabetic Zucker rats have more senescent endothelial cells than age-matched lean Zucker rats [66].…”

“…It has been shown that continuous angiotensin-converting enzyme (ACE) inhibition can ameliorate the age-related loss in renal function independent of blood pressure [99], and as discussed earlier, antihypertensive treatment could ameliorate hypertensive nephropathy and at the same time prevent further SCS marker increases in the kidney [45,46]. Some of the effects were independent of blood pressure reduction, and one could speculate that there are direct effects of the renin-angiotensin-aldosterone system on SCS pathways [46]. There is further evidence indicating a relationship between t SCS prevention and cardiovascular disease prevention.…”

“…Hypertension also induces SCS in kidney [45,46] and heart [45] in rodent models. Antihypertensive therapy prevents increases in p16 INK4a expression [45] and ameliorates telomere shortening [46].…”

“…Antihypertensive therapy prevents increases in p16 INK4a expression [45] and ameliorates telomere shortening [46]. This is accompanied by a milder histopathological phenotype mainly through reduced tubular atrophy and interstitial fibrosis.…”