RENAL-ARTERY STENOSIS RAPIDLY ENHANCES ATRIAL-NATRIURETIC-PEPTIDE GENE-EXPRESSION

The aim of this study was to examine the influence of the systemic ren in-angiotensin system on the gene expression of atrial natriuretic pep tide in rat hearts. The renin-angiotensin system was stimulated (1) by unilateral renal artery clipping (0.2-mm clip, 2 days), producing a f ourfold increase of circulating plasma renin activity and increasing b lood pressure. (2) by furosemide infusion with simultaneous salt subst itution, increasing plasma renin activity values to 45 ng angiotensin I/h per milliliter without changing blood pressure; or (3) by administ ration of the calcium antagonist amlodipine, which increased plasma re nin activity values to 42 ng angiotensin I/h per milliliter and lowere d blood pressure. Unilateral renal artery clipping increased atrial na triuretic peptide mRNA levels approximately 20-fold in the left ventri cles and approximately twofold in the right ventricles and atria. Furo semide infusion had no effect on cardiac atrial natriuretic peptide mR NA levels, and in amlodipine-treated rats, cardiac atrial natriuretic peptide mRNA levels decreased to 30% of control values. The increase o f atrial natriuretic peptide mRNA in the ventricles during renal arter y clipping was blunted by the administration of the angiotensin-conver ting enzyme inhibitor ramipril, which also attenuated the blood pressu re rise. In clipped rats amlodipine did not change elevated plasma ren in activity values but abolished the rise of blood pressure and also a ttenuated the rise of atrial natriuretic peptide mRNA in the hearts. T hese findings indicate that an increase of the activity of the systemi c renin-angiotensin system does not result in an obligatory change in cardiac atrial natriuretic peptide expression. Moreover, our results s uggest that activation renin-angiotensin system by renal artery stenos is preferentially stimulates left ventricular atrial natriuretic pepti de gene expression by an angiotensin II-dependent mechanism that could be associated with the induction of myocardial hypertrophy.