Lg. Bianciotti et Aj. De Bold, Modulation of cardiac natriuretic peptide gene expression following endothelin type A receptor blockade in renovascular hypertension, CARDIO RES, 49(4), 2001, pp. 808-816
Citations number
20
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Objective: Increased expression of the cardiac natriuretic peptides (NP), a
trial natriuretic factor (ANF) and brain natriuretic peptide (BNP) is obser
ved during chronic hemodynamic overload. The mechanisms underlying this pro
cess are not fully understood. In vitro, endothelin I (ET-1) is a powerful
stimulator of cardiac NP and, therefore, has been assumed to be one possibl
e mediator of increased NP gene expression following chronic pressure or Vo
lume overload. In the present work we investigated the possible role of ET-
1 in mediating the observed upregulation of cardiac NP in two kidney-one cl
ip (2K-1C) Goldblatt hypertensive rats treated for 6 weeks with the ET-1 ty
pe A. (ET,) receptor subtype receptor antagonist ABT-627. Methods: 2K-1C hy
pertension was induced in male Sprague-Dawley rats weighing 100-125 g by pl
acing a silver dip (internal diameter 0.25 mm) around the left renal artery
through a flank incision. The right kidney was left undisturbed. Sham oper
ated rats underwent the same experimental procedures but no clip was placed
on the left renal artery. ABT-627 was administered (10 mg/kg per day) in t
he drinking water for 6 weeks. Results: In hypertensive rats, ABT-627 preve
nted a further rise in blood pressure beginning at 3 weeks after clipping a
nd reduced the ventricular hypertrophy observed at the end of the experimen
t. ETA blockade prevented enhanced NP gene expression in the right ventricl
e and partially prevented it in the left ventricle. No modifications in atr
ial NP gene expression were observed in either control or 2K-1C animals. ET
A blockade decreased BNP circulating levels but did not affect ANF plasma l
evels in clipped rats. ABT-627 increased cr-myosin heavy chain gene express
ion and decreased the abundance of the beta isoform transcript. Conclusion:
The results obtained in the present investigation show the participation o
f ET-1 in the increased expression of ventricular NP in 2K-1C renovascular
hypertension and an apparent lack of effect of ETA blockade on atrial NP ge
ne expression in both control and hypertensive animals thus showing that in
vivo, atrial and ventricular NP gene expression are differentially regulat
ed. (C) 2001 Elsevier Science B.V. All rights reserved.