ATRIAL-NATRIURETIC-PEPTIDE GENE DELIVERY ATTENUATES HYPERTENSION, CARDIAC-HYPERTROPHY, AND RENAL INJURY IN SALT-SENSITIVE RATS

To investigate potential therapeutic effects of atrial natriuretic pep tide (ANP) gene delivery on renal and cardiac disorders, adenovirus ha rboring the human ANP gene (Ad.RSV-cANP) was delivered into Dahl salt- sensitive (DSS) rats on a high-salt diet. A single intravenous injecti on of the ANP gene caused a significant delay of blood pressure increa se 3 days post-injection and the effect lasted for more than 5 weeks. A maximal blood pressure reduction of 32.8 mmHg was observed after ANP gene delivery, as compared with that of control rats injected with Ad .CMV-LacZ. Immunoreactive human ANP can be detected in the heart, lung , and kidney of rats after gene delivery, ANP gene delivery caused sig nificant increases in renal blood flow, glomerular filtration rate, so dium output, urine excretion, and urinary cGMP levels, These beneficia l effects were reflected morphologically by a reduction in cardiomyocy te size, attenuation of the glomerular-sclerotic lesions, tubular inju ry and arterial thickening. This study demonstrated the usefulness of somatic gene transfer as a new tool for ANP gene delivery in studying salt-related hypertension and renal and cardiovascular diseases, In ad dition, the findings also suggest that ANP gene delivery may have pote ntial in therapeutic applications.