INTERACTION OF GENE AND SALT DIETS ON CARDIAC ANGIOTENSIN II, ALDOSTERONE, AND CYTOKINES IN HYPERTROPHIED HEART


Kailash N. Pandey, Ph.D., Tulane University School of Medicine, LA, USA

The objective of the present study was to elucidate the interactive roles of guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA) gene (Npr1) and salt diets on cardiac angiotensin II (ANG II), aldosterone (ALDO), and pro-inflammatory cytokines in hypertrophied hearts. Npr1 genotypes included gene-disrupted heterozygous (+/-; 1-copy), wild-type (+/+; 2-copy), gene-duplicated heterozygous (++/+; 3-copy), and gene-duplicated homozygous (++/++; 4-copy) mice. Animals were fed with low, normal, and high salt-diets. Cardiac and plasma ANG II, ALDO, and pro-inflammatory cytokines were determined. The results showed that cardiac ANG II and ALDO levels were greatly increased in Npr1 gene-disrupted 1-copy mice having hypertrophied hearts, however, greatly reduced in Npr1 gene-duplicated 3-copy and 4-copy mice. High salt-diet showed a significant baseline elevation of pro-inflammatory cytokines in 1-copy mice but the magnitude of elevation were only minimal in 3-copy and 4-copy mice compare with 2-copy wild-type control mice. The results showed that high salt-diet greatly elevated ANG II, ALDO, and pro-inflammatory cytokines in 1-copy mice, however, gene-duplicated mice did not render such elevated effect indicating the potential role of Npr1 gene against salt loading. The present results suggest that ANP/NPRA/cGMP signaling decreases cardiac ANG II, ALDO, and pro-inflammatory cytokines levels and protects heart from salt loading and cardiac remodeling process in the disease states.