Medullar expression of type-A natriuretic peptide receptor in an animal model of hypertension induced by renal mass ablation.
BACKGROUND
The biological activity of the natriuretic peptide (NP) system is dependent on the balance between NP tissue levels and the local expression of their receptors. In the kidney, the natriuretic peptide receptor type A (NPR-A) is the principal receptor mediating NP activity and is mainly expressed in the renal medulla. An increase in circulating NP levels is well documented in chronic renal failure (CRF); however, the renal expression of NPR-A has not been evaluated in this condition.


METHODS
Wistar-Han rats were submitted to right nephrectomy plus ablation of both poles of the left kidney (3/4nx; n=27) or were sham operated (Sham; n=22) and followed for up to 26 weeks post surgery. Blood pressure measurements were performed weekly. Two, 10 and 26 weeks after surgery, renal sodium and creatinine excretion were evaluated and the kidneys removed for NPR-A mRNA quantification by real-time PCR. The results of mRNA quantification are expressed in arbitrary units (AU) set as the mean value of the Sham group (Sham=1 AU), after normalization for GAPDH (p<0.05). weeks after surgery) and in elevated fractional sodium excretion (+270%, 26 weeks after surgery). Although sodium intake was similar in 3/4nx and Sham rats, blood pressure was higher in 3/4nx rats and increased progressively throughout the study. This was accompanied by a marked decrease in NPR-A mRNA levels in the renal medulla from 3/4nx animals at 2, 10 and 26 weeks post surgery.


CONCLUSIONS
In 3/4nx rats, the expression of NPR-A in the renal medulla of the remnant kidney is markedly reduced from 2 weeks up to 26 weeks post surgery. It is suggested that this may contribute to the progressive increase in blood pressure, as well as to the renal fibrosis observed in 3/4nx rats.
Araújo
Carla Santos
CS
Unidade de Investigação e Desenvolvimento de Nefrologia, Faculdade de Medicina, Porto, Portugal.
Albuquerque
Roberto Roncon
RR
Rodrigues
Mónica Moreira
MM
Maia
Benedita Sampaio
BS
Moreira
Adelino F Leite
AF
Pestana
Manuel
M
D000818:Animals; D004195:Disease Models, Animal; D006162:Guanylate Cyclase / Q000096:biosynthesis*; D006973:Hypertension / Q000209:etiology / Q000378:metabolism*; D007679:Kidney Medulla / Q000378:metabolism*; D008297:Male; D009392:Nephrectomy; D051381:Rats; D017208:Rats, Wistar; D017461:Receptors, Atrial Natriuretic Factor / Q000096:biosynthesis*
D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; C091715:atrial natriuretic factor receptor A