Reciprocal role of the AT1 receptor in modulating renal and neuronal AT1 mRNA expression
| Autor: | J, Li, H, Zhao, D J, Dipette, S C, Supowit, D H, Wang |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Male
Receptors Angiotensin Calcitonin Gene-Related Peptide Biphenyl Compounds Tetrazoles Angiotensin-Converting Enzyme Inhibitors Kidney Receptor Angiotensin Type 2 Receptor Angiotensin Type 1 Rats Ramipril Hypertension Animals Benzimidazoles Neurons Afferent RNA Messenger Angiotensin I Rats Wistar Antihypertensive Agents |
| Zdroj: | Journal of the American Society of Nephrology : JASN. 10 |
| ISSN: | 1046-6673 |
| Popis: | This study was designed to explore the mechanisms mediating the expression of the type 1 angiotensin II (AngII) receptor (AT1) in neuronal and renal tissues. Four groups of rats were given 1% NaCl in water and subjected to the renal reduced mass protocol (RRM), RRM + ramipril (Ram, 10 mg/kg per d), RRM + candesartan (Can, 10 mg/kg per d), or sham surgery. After 12 d, mean arterial pressure (MAP) was significantly higher in RRM rats than in RRM + Ram, RRM + Can, and sham-operated rats. Northern blot analysis showed that renal AT1 receptor mRNA levels (AT1 mRNA/18 rRNA) were significantly decreased in RRM (1.08+/-0.05) and RRM + Ram (0.82+/-0.02) compared with sham-operated rats (1.38+/-0.06) and that candesartan treatment caused a further decrease in renal AT1 mRNA content (0.73+/-0.07) compared with RRM. In contrast, dorsal root ganglia AT1 receptor mRNA content was significantly decreased in RRM (0.52+/-0.06) compared with sham-operated rats (1.18+/-0.07), and this decrease was abolished by ramipril (1.40+/-0.13) and candesartan treatment (1.56+/-0.11). RIA showed that levels (ng/mg protein) of calcitonin gene-related peptide (CGRP) in the dorsal root ganglia were significantly increased in RRM (1.60+/-0.11) but not in RRM + Ram (1.14+/-0.20) and RRM + Can (1.18+/-0.09), compared with sham-operated rats (0.94+/-0.05). Thus, RRM-induced downregulation of neuronal AT1 mRNA expression is mediated by AngII activation of the AT1 receptor, whereas an AT1-independent mechanism is operant in mediating renal AT1 gene expression. Furthermore, the inverse relationship between neuronal AT1 expression and CGRP content indicates that activation of the neuronal AT1 receptor inhibits CGRP synthesis in the dorsal root ganglia. The functional implications of these findings are discussed. |
| Databáze: | OpenAIRE |
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