Renal c-fos expression induced by angiotensin II is enhanced in spontaneously hypertensive rats.
We compared the effect of a bolus injection of angiotensin II (Ang II) on the expression of protooncogene c-fos in the renal cortex and medulla of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. Intravenous infusion of 5 ng/kg body weight of Ang II resulted in an immediate rise in systolic blood pressure (SBP) in both SHR and WKY rats. The percent rise in SBP was similar in both strains. Pretreatment with Ang II type 1 (AT1)-receptor antagonist, L-158,809 (1 mg/kg) abolished the pressor response in both strains. Competitive reverse transcription-polymerase chain reaction (RT-PCR) showed that administration of Ang II increased the expression of c-fos mRNA within 10 min in both the renal cortex and medulla of SHR significantly higher than WKY rats. Moreover, the enhanced c-fos mRNA expression due to Ang II was significantly suppressed by the pretreatment of L-158,809 in both strains. These findings indicate that c-fos expression in the kidney is mediated by AT1-receptors and that the renal c-fos response to exogenous Ang II was significantly augmented in SHR compared with WKY rats, suggesting that this hyperresponsiveness on renal AT1-action may partly contribute to the progression of renal injury in SHR.
Otsuka
F
F
Department of Medicine III, Okayama University Medical School, Japan.
Yamauchi
T
T
Ogura
T
T
Takahashi
M
M
Kageyama
J
J
Makino
H
H
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects*; D016762:Genes, fos / Q000235:genetics*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D007093:Imidazoles / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D007093:Imidazoles; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013777:Tetrazoles; D000804:Angiotensin II; C070967:L 158809