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• W1838353535 abstract "A potential role for the renin-angiotensin system (RAS) in the development and/or maintenance of hypertension in the genetic model of rat hypertension, spontaneously hypertensive rats (SHR), has been suggested by studies indicating that treatment of immature animals with angiotensin-converting enzyme (ACE) inhibitors prevents subsequent development of hypertension. Because young SHR also demonstrate RAS-dependent increased sodium retention, we examined proximal tubule type 1 angiotensin II receptor (AT 1 R) mRNA expression in young (4 wk) or adult (14 wk) SHR compared with age-matched Wistar-Kyoto (WKY) rats. Proximal tubules were isolated by Percoll gradient centrifugation, and AT 1 R mRNA expression was measured by quantitative reverse transcription-polymerase chain reaction (RT-PCR). At 14 wk, when SHR had established hypertension [mean arterial blood pressure (MAP) of SHR vs. WKY: 145 ± 6 vs. 85 ± 5 mmHg, n = 14–15], there were no differences in proximal tubule AT 1 R mRNA levels [SHR vs. WKY: 79 ± 14 vs. 72 ± 14 counts/min (cpm) per cpm mutant AT 1 R per cpm β-actin × 10 −6 , n = 6; not significant (NS)]. In contrast, in 4 wk SHR, at a time of minimal elevations in blood pressure (MAP: 70 ± 8 vs. 63 ± 3), SHR proximal tubule AT 1 R mRNA levels were 263 ± 30% that of WKY (143 ± 18 vs. 60 ± 11 cpm per cpm of mutant AT 1 R per cpm β-actin × 10 −6 , n = 8; P < 0.005). We have recently shown that chronic ACE inhibition decreases proximal tubule AT 1 R expression and have also shown that chronicl-3,4-dihydroxyphenylalamine (l-DOPA) administration inhibits AT 1 R expression in adult Sprague-Dawley proximal tubule and cultured proximal tubule, and this inhibition is mediated via G s -coupled DA 1 receptors. When 3-wk-old animals were given l-DOPA or captopril for 1 wk, MAP was not altered (70 ± 8 vs. 60 ± 4 or 61 ± 5 mmHg), but proximal tubule AT 1 R mRNA was no longer significantly different between SHR and WKY (68 ± 9 vs. 38 ± 7 or 20 ± 3 vs. 47 ± 15 cpm per cpm of mutant AT 1 R per cpm β-actin × 10 −6 ), due to a significant decrease in proximal tubule AT 1 R expression in SHR ( P < 0.005, compared with untreated SHR). Immunoreactive proximal tubule AT 1 R expression also was increased in 4 wk SHR and was reversed with captopril orl-DOPA treatment. Therefore, these results indicate that young, but not adult, SHR have increased expression of proximal tubule AT 1 R and that chronic l-DOPA or captopril treatment decreased the elevated AT 1 R expression to control levels. These results provide further support for an important role of the RAS in the development of hypertension in SHR." @default.
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• W1838353535 date "1998-01-01" @default.
• W1838353535 modified "2023-10-18" @default.
• W1838353535 title "Young SHR express increased type 1 angiotensin II receptors in renal proximal tubule" @default.
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• W1838353535 doi "https://doi.org/10.1152/ajprenal.1998.274.1.f10" @default.
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