Upregulation of AT1R and iNOS in the rostral ventrolateral medulla (RVLM) is essential for the sympathetic hyperactivity and hypertension in the 2K-1C Wistar rat model.
BACKGROUND
We hypothesized that upregulation of angiotensin type 1 receptor (AT(1)R) and inducible nitric oxide (NO) synthase (iNOS) within the rostral ventrolateral medulla (RVLM) could contribute to two-kidney, one-clip (2K-1C) hypertension.


METHODS
The experiments were performed in male Wistar rats, 6 weeks after the renal surgery. The animals were divided into control (SHAM, n = 18) and hypertensive groups (2K-1C, n = 18). Bilateral tissue punches were taken from sections containing the RVLM to perform iNOS gene expression analyses by the real-time PCR technique, and AT(1)R and iNOS protein expression analyses by western blotting. In addition, we injected losartan (1 nmol), an AT(1)R antagonist, and aminoguanidine (250 pmol), an iNOS inhibitor, bilaterally into the RVLM to analyze the mean arterial pressure (MAP) and renal sympathetic nerve activity (rSNA).


RESULTS
iNOS mRNA expression levels were greater (P < 0.05) in the 2K-1C group compared to the SHAM group. Furthermore, the AT(1)R and iNOS protein expression were significantly increased in the RVLM of 2K-1C rats compared to SHAM rats. Injection of losartan into the RVLM reduced the MAP (11%) and rSNA (18%) only in the 2K-1C rats, whereas injection of aminoguanidine in the same region decreased the MAP (31%) and rSNA (34%) in hypertensive rats.


CONCLUSIONS
The present study suggests that upregulation of AT(1)R and iNOS in the RVLM is important in the maintenance of high blood pressure and renal sympathetic activation in 2K-1C hypertension.
de Oliveira-Sales
Elizabeth Barbosa
EB
Cardiovascular Division, Department of Physiology, Federal University of Sao Paulo, São Paulo, Brazil.
Nishi
Erika Emy
EE
Boim
Mirian Aparecida
MA
Dolnikoff
Miriam Sterman
MS
Bergamaschi
Cássia T
CT
Campos
Ruy R
RR
D000818:Animals; D001933:Brain Stem / Q000378:metabolism*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D015870:Gene Expression; D006146:Guanidines / Q000008:administration & dosage; D006978:Hypertension, Renovascular / Q000378:metabolism / Q000503:physiopathology*; D007668:Kidney / Q000294:innervation* / Q000503:physiopathology; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014176:Protein Biosynthesis; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000378:metabolism / Q000503:physiopathology*; D015854:Up-Regulation
D004791:Enzyme Inhibitors; D006146:Guanidines; D044140:Receptor, Angiotensin, Type 1; D052247:Nitric Oxide Synthase Type II; C004479:pimagedine