Inhibition of hypoxic pulmonary vasoconstriction in isolated rat resistance arteries by atrial natriuretic peptide.
Atrial natriuretic peptide (ANP) is a vasodilator secreted by the heart in response to right atrial stretch. We have hypothesized that ANP may be released to attenuate pulmonary hypertension due to hypoxia. We have examined whether ANP inhibits hypoxic pulmonary vasoconstriction (HPV) in isolated pulmonary resistance vessels (PRV) from chronically hypoxic (CH) rats, compared to air-breathing, control (C) rats. After at least 17 days of chronic hypoxia, vessels (n = 29) were dissected from CH and C littermates and mounted in an automated myograph. The inhibitory effect of ANP on the rapid first contractile phase of HPV, and the relaxant effect of ANP on vessels tonically contracted in the second phase of HPV, were studied. ANP caused concentration-dependent inhibition of HPV in both C and CH vessels (p < 0.001), whilst vehicle had no effect (mean maximum inhibition was 88 and 101%, respectively, at 17 nM ANP). ANP also caused significant concentration-dependent relaxation of the second contractile phase of HPV, which was similar in C and CH vessels (mean maximum relaxation of 89 and 94%, respectively; median effective concentrations were 2.4 and 2.0 nM, respectively). We conclude that atrial natriuretic peptide is a potent antagonist of both contractile phases of hypoxic pulmonary vasoconstriction in isolated rat pulmonary resistance vessels at concentrations similar to those observed in hypoxic pulmonary hypertension in life. There was no difference between vessels from chronically hypoxic and control animals.
Rogers
T K
TK
Dept of Medicine, University of Sheffield, Northern General Hospital, UK.
Thompson
J S
JS
Morice
A H
AH
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology / Q000502:physiology*; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000503:physiopathology; D000860:Hypoxia / Q000150:complications / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D011651:Pulmonary Artery / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D009320:Atrial Natriuretic Factor