Humoral pulmonary vasoregulation in conscious dogs after left lung autotransplantation.
We investigated the roles of cyclooxygenase metabolites, arginine vasopressin (AVP) and angiotensin II (ANG II), as mediators of the chronic increase in pulmonary vascular resistance associated with left lung autotransplantation (LLA) in conscious dogs. Continuous left pulmonary vascular pressure-flow (LP-Q) plots were generated in conscious dogs 2- to 5-wk post-LLA and in sham-operated control conscious dogs. LLA resulted in a marked shift (P < 0.01) in the LP-Q relationship as reflected by an approximate doubling of the pulmonary vascular pressure gradient at each common value of left pulmonary blood flow compared with the control group. Cyclooxygenase pathway inhibition (indomethacin) and AVP V1-receptor block had no effect on the LP-Q relationship post-LLA. Angiotensin-converting enzyme inhibition (captopril) also failed to reverse the increase in pulmonary vascular resistance post-LLA. Because captopril has the dual effect of inhibiting the production of ANG II and the degradation of bradykinin, additional studies utilizing a selective ANG II receptor antagonist were performed. ANG II receptor block (saralasin) significantly altered the LP-Q relationship post-LLA to cause active pulmonary vasodilation (P < 0.01). Thus, the chronic increase in pulmonary vascular resistance post-LLA is not mediated by metabolites of the cyclooxygenase pathway or AVP V1-receptor activation. A significant component of the increase in pulmonary vascular resistance resulting from LLA is mediated by ANG II. The differential responses to captopril and saralasin may imply a pulmonary vasoregulatory role for bradykinin post-LLA.
Desai
P M
PM
Division of Cardiac Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287-4961.
Nishiwaki
K
K
Stuart
R S
RS
Nyhan
D P
DP
Murray
P A
PA
D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology; D004285:Dogs; D007213:Indomethacin / Q000494:pharmacology; D016040:Lung Transplantation; D008297:Male; D011652:Pulmonary Circulation / Q000187:drug effects; D012504:Saralasin / Q000494:pharmacology; D014182:Transplantation, Autologous; D014666:Vasomotor System / Q000502:physiology*
D065092:Antidiuretic Hormone Receptor Antagonists; D002216:Captopril; D012504:Saralasin; D007213:Indomethacin