Augmentation of BNP gene expression in atria by pressure overload in transgenic rats harbouring human renin and angiotensinogen genes

Abstract

We studied the role of angiotensin II in pressure overload-induced B-type natriuretic peptide (BNP) gene expression by using a double transgenic rat (dTGR) model, in which transgenic rats for the human angiotensinogen and renin genes are crossed. Pressure overload produced by [Arg8]-vasopressin (AVP) infusion (i.v., 0.05 microg/kg/min for 2 h) in conscious, chronically instrumented rats, resulted in a significantly greater increase in BNP mRNA levels in the left atrium of the dTGR rats than in Sprague-Dawley (SD) control rats (3.6- vs 1.6-fold, p < 0.05), while in the left ventricle there was no significant difference between the strains. In dTGR rats, the early activation of the BNP gene expression was associated with a decrease in immunoreactive BNP levels in the atrium (27.5%, p < 0.05), but not in the ventricle. In SD rats, ir-BNP levels did not change significantly in either atria or ventricles in response to AVP infusion. These results show that the pressure overload-induced activation of BNP gene expression differs between atrial and ventricular myocytes in the dTGR model of experimental hypertension.

Posttranscriptional Control of BNP Gene Expression in Angiotensin II–Induced Hypertension

“…Yet, transgenic rats overexpressing human renin and angiotensinogen genes have normal left ventricular BNP mRNA levels even in established phase of hypertension and severe myocardial hypertrophy. 18 Lack of an increase in ventricular BNP mRNA levels has also been observed in some patients with heart failure. 19,20 To determine whether alterations in the rate of transcription of the BNP gene could account for the changes observed in BNP mRNA levels, we measured the activity of a Ϫ2.2-kbp BNP promoter fragment fused to the luciferase reporter gene by injecting it directly into beating left ventricle.…”

“…8 -10 However, controversy persists regarding to BNP gene expression in ventricular myocardium under normal conditions and in chronic cardiac overload. Indeed, conflicting studies both in the human and in animals describe either increased 9,[11][12][13][14] or unchanged left ventricular BNP mRNA levels [15][16][17][18][19][20] in heart failure and hypertension. The reason for the normal BNP mRNA levels despite constant cardiac overload is not known but could result from transcriptional and/or translational mechanisms.…”

Milk Products Containing Bioactive Tripeptides Have an Antihypertensive Effect in Double Transgenic Rats (dTGR) Harbouring Human Renin and Human Angiotensinogen Genes

“…With this rat model, therefore, ACE inhibition does not seem to explain the blood pressure lowering effect in the fermented milk group. According to a previous study [36], the plasma concentration of BNP was elevated in dTGRs related to cardiac pressure. The peptide treatments in this study were not able to antagonise clearly this increase.…”

Regulation of cardiac melusin gene expression by hypertrophic stimuli in the rat

“…Then arginine 8 -vasopressin (AVP) at a dose of 0.05 lg kg À1 min À1 or vehicle (0.9% NaCl) was infused i.v. at 37.5 lL min À1 for 30 min, 1 h or 4 h. In another series of experiments, AVP was infused for 30 min or 4 h in SHR and WKY rats and for 2 h in dTGR rats (Marttila et al 1999). Ang II (33 lg kg À1 h À1 ), vehicle (0.9% NaCl), angiotensin II type 1 receptor (AT 1 -R) antagonist losartan (400 lg kg À1 h À1 ) or Ang II + losartan was infused for 6, 12 or 72 h or 2 weeks via subcutaneously implanted osmotic minipumps (Alzet, Durect corporation, Cupertino, CA, USA) in SD rats as described previously (Rys€ a et al 2006).…”