Differential expression of natriuretic peptides and their receptors in volume overload cardiac hypertrophy in the rat

Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) upregu lation are genetic markers for the chronic hypertrophic phenotype but also have important acute physiologic effects on salt and water balance and bloo d pressure control. The presence of a dual NP-system led us to hypothesize a differential expression of ANP and BNP in response to an acute hemodynami c stress of volume overload in the left ventricle (LV) and right ventricle (RV). Accordingly, we examined the temporal relationship between the RV and LV expression of ANP and BNP mRNA and NP receptor mRNA levels on days 1, 2 , 3, and 7 after induction of aortocaval fistula in the rat. LV end-diastol ic pressure was increased 1.5-fold by day 3 and 2.0-fold by day 7 compared to control (P<0.05). LV weight increased by day 7 compared to control (2.34 +/- 0.04 vs 3.07 +/- 0.10 mg/g, P<0.05) while RV weight did not change ove r the 7 days. There was a 7-fold increase of ANP mRNA in LV at day 1, which was sustained through day 7, while LV BNP mRNA levels did not differ from controls over the 7 days. In contrast, RV mRNA transcript levels for ANP an d BNP were increased >2-fold by day 2 and this increase was sustained throu ghout 7 days, NP clearance receptor was decreased by 75% by day 7 in the LV but did not change in the RV. Thus, LV ANP mRNA levels increased before th e onset of LV hypertrophy and RV BNP mRNA levels increased in the absence o f RV hypertrophy. The disparate response of BNP and the NP clearance recept or transcript levels in the LV and RV may be related to differences in load and/or differential expression of the NP system in the LV and RV in respon se to acute haemodynamic stress. (C) 1999 Academic Press.