ARB treatment prevented increases in systolic BP, renal Ang II, and renal injury in spontaneously hypertensive rats, whereas triple therapy prevented hypertension but failed to prevent renal injury.
Does ARB or triple antihypertensive therapy prevent renal injury and reduce intrarenal angiotensinogen in spontaneously hypertensive rats?
ARB therapy, but not standard triple antihypertensive therapy, prevents early renal injury in spontaneously hypertensive rats by reducing intrarenal angiotensinogen and Ang II levels.
This study was performed to determine whether augmented intrarenal angiotensinogen may contribute to the enhanced renal angiotensin II (Ang II) and associated tissue injury in spontaneously hypertensive rats (SHR). SHR and Wistar-Kyoto rats (WKY) were maintained on a normal diet and killed at either 7 or 14 wk of age. Two groups of SHR received either an Ang II type 1 receptor blocker (ARB; olmesartan, 5 mg/d) or a triple therapy (hydralazine 7.5 mg/d, reserpine 0.15 mg/d, and hydrochlorothiazide 3 mg/d HRH) during weeks 7 through 14. Systolic BP and renal Ang II were significantly increased in SHR-14 (n = 8) compared with WKY-7, WKY-14, and SHR-7 (n = 8 each), and ARB treatment prevented these increases (n = 8). However, whereas HRH treatment prevented the development of hypertension in SHR, this combination therapy failed to decrease renal Ang II (n = 8). With the use of urine samples or fixed renal sections, renal injuries in rats were quantified in a semiautomated manner by the following six parameters: (1) urinary excretion rate of total protein, (2) glomerular sclerosis, (3) interstitial expansion, (4) and (5) numbers of monocytes/macrophages in interstitium or glomeruli, and (6) arterial proliferation. Angiotensinogen mRNA and protein levels in kidney cortex, measured by real-time reverse transcriptase-PCR and Western blot analysis, respectively, and all six parameters of renal damage were changed in parallel, and ARB treatment also prevented these increases. However, HRH treatment failed to prevent these increases. These results indicate that SHR have enhanced intrarenal angiotensinogen production that contributes to increased Ang II levels leading to the development of hypertension and renal injury in this strain.
Kobori et al. (Thu,) conducted a other in Hypertension and renal injury (n=48). Angiotensin II type 1 receptor blocker (olmesartan) or triple therapy (hydralazine, reserpine, hydrochlorothiazide) vs. Untreated SHR and WKY rats was evaluated on Systolic blood pressure, renal Angiotensin II levels, and renal injury parameters. ARB treatment prevented increases in systolic BP, renal Ang II, and renal injury in spontaneously hypertensive rats, whereas triple therapy prevented hypertension but failed to prevent renal injury.
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