The role of the renin-angiotensin and natriuretic peptide systems in the pulmonary vasculature.
1. The role of vasoactive peptide systems in the pulmonary vasculature has been studied much less extensively than systemic vascular and endocrine effects. The current understanding of the role of the renin-angiotensin (RAS) and natriuretic peptide systems (NPS) in the pulmonary circulation is therefore reviewed. 2. Plasma concentrations of angiotensin II, the main vasoactive component of the RAS, are elevated in pulmonary hypertension and may interact with hypoxaemia to cause further pulmonary vasoconstriction. Pharmacological manipulation of angiotensin II can attenuate hypoxic pulmonary vasoconstriction but larger studies are needed to establish the efficacy of this therapeutic strategy in established pulmonary hypertension. 3. Although all the known natriuretic peptides, ANP, BNP and CNP are elevated in cor pulmonale, only ANP and BNP appear to have pulmonary vasorelaxant activity in humans. ANP and BNP can also attenuate hypoxic pulmonary vasoconstriction, suggesting a possible counter-regulatory role for these peptides. Inhibition of ANP/BNP metabolism by neutral endopeptidase has been shown to attenuate development of hypoxic pulmonary hypertension but this property has not been tested in humans. 4. It is also well established that there are potentially important endocrine and systemic circulatory interactions between the RAS and NPS. This also occurs in the pulmonary circulation and in humans, where at least BNP acts to attenuate angiotensin II induced pulmonary vasoconstriction. This interaction may be particularly relevant as a mechanism to counter-regulate overactivity of the RAS.(ABSTRACT TRUNCATED AT 250 WORDS)
Cargill
R I
RI
Department of Clinical Pharmacology, Ninewells Hospital and Medical School, Dundee, Scotland, UK.
Lipworth
B J
BJ
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000097:blood / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood / Q000188:drug therapy; D000860:Hypoxia / Q000503:physiopathology; D020097:Natriuretic Peptide, Brain; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects* / Q000502:physiology; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D009419:Nerve Tissue Proteins; D000804:Angiotensin II; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor