Jr. Klinger et al., C-TYPE NATRIURETIC PEPTIDE EXPRESSION AND PULMONARY VASODILATION IN HYPOXIA-ADAPTED RATS, American journal of physiology. Lung cellular and molecular physiology, 19(4), 1998, pp. 645-652
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.