C-TYPE NATRIURETIC PEPTIDE EXPRESSION AND PULMONARY VASODILATION IN HYPOXIA-ADAPTED RATS

Atrial and brain natriuretic peptides (ANP and BNP, respectively) are potent pulmonary vasodilators that are upregulated in hypoxia-adapted rats and may protect against hypoxic pulmonary hypertension. To test t he hypothesis that C-type natriuretic peptide (CNP) also modulates pul monary vascular responses to hypoxia, we compared the vasodilator effe ct of CNP with that of ANP on pulmonary arterial rings, thoracic aorti c rings, and isolated perfused lungs obtained from normoxic and hypoxi a-adapted rats. We also measured CNP and ANP levels in heart, lung, br ain, and plasma in normoxic and hypoxia-adapted rats. Steady-state CNP mRNA levels were quantified in the same organs by relative RT-PCR. CN P was a less potent vasodilator than ANP in preconstricted thoracic ao rtic and pulmonary arterial rings and in isolated lungs from normoxic and hypoxia-adapted rats. Chronic hypoxia increased plasma CNP (15 +/- 2 vs. 6 +/- 1 pg/ml; P < 0.05) and decreased CNP in the right atrium (35 +/- 14 vs. 65 +/- 17 pg/mg protein; P < 0.05) and in the lung (3 /- 1 vs. 14 +/- 3 pg/mg protein; P < 0.05) but had no effect on CNP in brain or right ventricle. Chronic hypoxia increased ANP levels fivefo ld in the right ventricle (49 +/- 5 vs. 11 +/- 2 pg/mg protein; P < 0. 05) but had no effect on ANP in lung or brain. There was a trend towar d decreased ANP levels in the right atrium (2,009 +/- 323 vs. 2,934 +/ - 397 pg/mg protein; P = not significant). No differences in CNP trans cript levels were observed between the two groups of rats except that the right atrial CNP mRNA levels were lower in hypoxia-adapted rats. W e conclude that CNP is a less potent pulmonary vasodilator than ANP in normoxic and hypoxia-adapted rats and that hypoxia raises circulating CNP levels without increasing cardiopulmonary CNP expression. These f indings suggest that CNP may be less important than ANP or BNP in prot ecting against hypoxic pulmonary hypertension in rats.