C-type natriuretic peptide upregulates vascular endothelin type B receptors

Cultured rat vascular smooth muscle cells (VSMCs) possess receptors for potent vasoconstrictor endothelin-1 (ET-1) as well as potent vasodilator natriuretic peptides (atrial, brain, and C-type natriuretic peptides [ANP, BNP, and CNP, respectively]). However, little is known about molecular interactions between endothelin receptors and natriuretic peptides in VSMCs. To elucidate whether natriuretic peptides regulate vascular endothelin receptors, we studied the effects of three natriuretic peptides on the capacity of 125I-ET-1 binding and expression of endothelin type A (ETA) and type B (ETB) receptor mRNAs in cultured rat VSMCs. CNP (10(-6) mol/L) increased 125I-ET-1 binding capacity in a time-dependent manner (6 to 48 hours) and stimulated cyclic GMP (cGMP) generation in a dose-dependent manner (10(-8)) to 10(-6) mol/L). Pretreatment with CNP (10(-8) to 10(-6) mol/L) and 8-bromo-cGMP (10(-5) to 10(-3) mol/L) for 24 hours resulted in dose-dependent increases in 125I-ET-1 binding in VSMCs. The three natriuretic peptides at the highest concentration (10(-6) mol/L) increased 125I-ET-1 binding and stimulated cGMP generation with almost the same rank order of efficacy (CNP > BNP > ANP). Scatchard analysis of binding studies revealed that CNP (10(-6) mol/L) and 8-bromo-cGMP (10(-3) mol/L) increased vascular endothelin receptor number by 28% and 88%, respectively, without changing its affinity. Pretreatment with both CNP and 8-bromo-cGMP increased ET-1-stimulated inositol 1,4,5-trisphosphate formation.(ABSTRACT TRUNCATED AT 250 WORDS)