Regulation of aortic atrial natriuretic factor and angiotensinogen in experimental hypertension.

Abstract

We investigated the relation between atrial natriuretic factor (ANF) gene expression and the status of the renin-angiotensin system (RAS) in aortic tissue in rats made hypertensive by either aortic banding or by deoxycorticosterone acetate (DOCA)-salt administration. These experimental models of hypertension are known to have differences in terms of the status of RAS. ANF messenger RNA (mRNA) levels were measured in aortic tissue by using a newly developed quantitative competitive reverse transcription polymerase chain reaction (QC-RT-PCR) technique. Changes in the proportions of alpha1 and alpha2 isoforms of Na+K+-adenosine triphosphatase (ATPase) mRNA levels were used as indicators of aortic hypertrophy. Treatment with DOCA alone, salt alone, or DOCA-salt for 5 weeks increased aortic-weight/body-weight ratio and aortic angiotensinogen mRNA levels, but did not change alpha1 or alpha2 Na+K+-ATPase mRNA levels. Aortic ANF mRNA levels had a tendency to increase after treatment with DOCA, salt, or DOCA-salt, but this change did not reach statistical significance. Suprarenal aortic banding for 6 weeks or 12 weeks increased aortic-weight/body-weight ratio (12 weeks), decreased alpha2 Na+K+-ATPase and angiotensinogen mRNA levels, but did not affect alpha1 Na+K+-ATPase mRNA levels or ANF mRNA levels. Treatment with ramipril, an angiotensin-converting enzyme (ACE) inhibitor was carried out for 6 weeks just after aortic banding (prevention experiment) or after 6 weeks in rats that were banded for the previous 6 weeks (regression experiment). High-dose ramipril (1 mg/kg)--a treatment known to inhibit both tissue and circulating RAS--normalized aortic-weight/body-weight ratio, and also normalized alpha2 Na+K+-ATPase mRNA levels. Aortic angiotensinogen mRNA levels of banded rats treated with high-dose ramipril was higher than those of the normal control, sham operated, and banded rats. Treatment with high-dose ramipril did not affect alpha1 Na+K+-ATPase mRNA levels or ANF mRNA levels. Low-dose ramipril (10 microg/kg)--a treatment that selectively inhibits tissue RAS--normalized aortic-weight/body-weight ratio but did not normalize alpha2 Na+K+-ATPase mRNA levels (regression experiment) or angiotensinogen mRNA levels (prevention experiment) and did not change either alpha1 Na+K+-ATPase mRNA levels or ANF mRNA levels. The results suggest that, in contrast to previous findings in heart and kidney, the regulation of ANF mRNA levels in aortic tissue is largely independent of pressure load, volume load, and plasma or tissue RAS. It is suggested that any antihypertrophic actions of ANF may be mediated by the increased circulating ANF levels and its interaction with its receptor or through CNP.