Endogenous angiotensin II in the regulation of hypoxic pulmonary vasoconstriction in anaesthetized dogs.
BACKGROUND
The role played by several vasoactive mediators that are synthesized and released by the pulmonary vascular endothelium in the regulation of hypoxic pulmonary vasoconstriction (HPV) remains unclear. As a potent vasoconstrictor, angiotensin II could be involved. We tested the hypothesis that angiotensin-converting enzyme inhibition by enalaprilat and type 1 angiotensin II receptor blockade by candesartan would inhibit HPV.


METHODS
HPV was evaluated in anaesthetized dogs, with an intact pulmonary circulation, by examining the increase in the Ppa-Ppao gradient (mean pulmonary artery pressure minus occluded pulmonary artery pressure) that occurred in response to hypoxia (inspiratory oxygen fraction of 0.1) at constant pulmonary blood flow. Plasma renin activity and angiotensin II immunoreactivity were measured to determine whether activation or inhibition of the renin-angiotensin system was present.


RESULTS
Administration of enalaprilat and candesartan did not affect the Ppa-Ppao gradient at baseline or during hypoxia. Plasma renin activity and angiotensin II immunoreactivity increased during hypoxia, and subsequent measurements were consistent with effective angiotensin-converting enzyme inhibition after administration of enalaprilat, and with angiotensin receptor blockade after administration of candesartan.


CONCLUSIONS
These results suggest that, although the renin-angiotensin system was activated in hypoxia, angiotensin II is not normally involved in mediating acute HPV.
Department of Intensive Care Medicine, Akademisch Ziekenhuis VUB, and Laboratory of Physiology, Faculty of Medicine, Erasme Campus of the Free University of Brussels, Brussels, Belgium. ives.hubloue@az.vub.ac.be
Ives
I
Hubloue
Benoît
B
Rondelet
François
F
Kerbaul
Dominique
D
Biarent
Guiti Malekzadeh
GM
Milani
Michel
M
Staroukine
Pierre
P
Bergmann
Robert
R
Naeije
Marc
M
Leeman
D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D004285:Dogs; D015773:Enalaprilat / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000378:metabolism; D000860:Hypoxia / Q000188:drug therapy* / Q000378:metabolism; D008168:Lung / Q000098:blood supply*; D023421:Models, Animal; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013777:Tetrazoles / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors* / Q000378:metabolism
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D015773:Enalaprilat; C081643:candesartan