Jr. Klinger et al., BRAIN NATRIURETIC PEPTIDE INHIBITS HYPOXIC PULMONARY-HYPERTENSION IN RATS, Journal of applied physiology, 84(5), 1998, pp. 1646-1652
Brain natriuretic peptide (BNP) is a pulmonary vasodilator that is ele
vated in the fight heart and plasma of hypoxia-adapted rats. To test t
he hypothesis that BNP protects against hypoxic pulmonary hypertension
, we measured right ventricular systolic pressure (RVSP), right ventri
cle (RV) weight-to-body weight (BW) ratio (RV/BW), and percent muscula
rization of peripheral pulmonary vessels (%MPPV) in rats given an intr
avenous infusion of BNP, atrial natriuretic peptide (ANP), or saline a
lone after 2 wk of normoxia or hypobaric hypoxia (0.5 arm). Hypoxia-ad
apted rats had higher hematocrits, RVSP, RV/BW, and %MPPV than did nor
moxic controls. Under normoxic conditions, BNP infusion (0.2 and 1.4 m
u g/h) increased plasma BNP but had no effect on RVSP, RV/BW, or %MPPV
. Under hypoxic conditions, low-rate BNP infusion (0.2 mu g/h) had no
effect on plasma BNP or on severity of pulmonary hypertension. However
, high-rate BNP infusion (1.4 mu g/h) increased plasma BNP (69 +/- 8 v
s; 35 +/- 4 pg/ml, P < 0.05), lowered RV/BW (0.87 +/- 0.05 vs. 1.02 +/
- 0.04, P < 0.05), and decreased %MPPV (60 vs. 74%, P < 0.05). There w
as also a trend toward lower RVSP (55 +/- 3 vs. 64 +/- 2, P = not sign
ificant). Infusion of ANP at 1.4 mu g/h increased plasma ANP in hypoxi
c rats (759 +/- 153 vs. 393 +/- 54 pg/ml, P < 0.05) but had no effect
on RVSP, RV/BW, or %MPPV. We conclude that BNP may regulate pulmonary
vascular responses to hypoxia and, at the doses used in this study, is
more effective than ANP at blunting pulmonary hypertension during the
first 2 wk of hypoxia.