MODULATION OF VASCULAR NATRIURETIC PEPTIDE RECEPTOR GENE-EXPRESSION IN HYPERTENSIVE AND OBESE HYPERGLYCEMIC RATS

Receptors for natriuretic peptide (NP) consist of three subtypes: NP-A , NP-S, and NP-C. Recent studies in cultured aortic cells have suggest ed a phenotype-related switching of the Vascular NP receptor from NP-A to NP-B. To ascertain the biological significance of the phenomenon i n vivo, we developed a sensitive and reproducible ribonuclease protect ion assay and determined each receptor messenger RNA (mRNA) level in t he vascular vessels of stroke-prone spontaneously hypertensive rats, d eoxycorticosterone acetate-salt hypertensive rats, and genetically hyp erglycemic Wistar fatty rats and in cultured aortic smooth muscle cell s. The aortic NP-A receptor mRNA level was significantly up-regulated in both types of hypertensive rats, whereas the NP-B receptor mRNA lev el did not show any significant change. Both NP-A and NP-B receptor mR NA levels were significantly up-regulated in Wistar fatty rats compare d with the control values. There was no significant up-regulation of N P-A receptor mRNA in the inferior vena cava of the stroke-prone sponta neously hypertensive rats. Although the NP-A receptor was always the p redominant subtype in rat aortic tissue, NP-B receptor was the predomi nant subtype in aortic smooth muscle cells in culture. These findings suggest that up-regulation of the NP-A receptor, but not the subtype s witching, is the major modulation of receptor gene expression in both hypertensive and diabetic rats.