Does endocardial endothelium mediate positive inotropic response to angiotensin I and angiotensin II?
The positive inotropic response to angiotensin I and II in cardiac tissue of most mammalian species, as well as the exact site in the heart for conversion of local and systemic angiotensin I into angiotensin II, remains to be elucidated. In isolated cat papillary muscles, angiotensin I and angiotensin II (0.1 nM to 1 microM, 35 degrees C, 1.25 mM Ca2+) increased, in a dose-dependent manner, peak twitch tension with typical slight prolongation of twitch duration. This typical response did not necessitate the presence of an intact endocardial endothelium (EE), as a similar response was observed in muscles where the EE had been damaged by a 1-second exposure to 0.5% Triton X-100. After addition of captopril, an angiotensin converting enzyme inhibitor, the positive inotropic response to angiotensin I was completely abolished, both in the presence and the absence of an intact EE. Hence, the heart possesses angiotensin converting enzyme, which mediates the positive inotropic response to angiotensin I. An intact EE was not a prerequisite for this response; thus, myocytes as well as nonmyocytes may be possible locations (in addition to the EE) for angiotensin converting enzyme. In the presence of an intact EE, and after addition of captopril, the positive inotropic response to angiotensin II was significantly diminished (desensitization). By contrast, in the absence of an intact EE, but also after addition of captopril, the positive response to angiotensin II was potentiated (sensitization). Both desensitization and sensitization (in the presence or absence of an intact EE, respectively) of the response to angiotensin II induced by the addition of captopril were inhibited by indomethacin, a cyclooxygenase inhibitor, suggesting a role for prostaglandins.
Meulemans
A L
AL
University of Antwerp, Belgium.
Andries
L J
LJ
Brutsaert
D L
DL
D000803:Angiotensin I / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D002216:Captopril / Q000494:pharmacology; D002415:Cats; D016861:Cyclooxygenase Inhibitors; D004699:Endocardium / Q000502:physiology* / Q000648:ultrastructure; D004727:Endothelium / Q000502:physiology / Q000648:ultrastructure; D066298:In Vitro Techniques; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D009200:Myocardial Contraction / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D016861:Cyclooxygenase Inhibitors; D000804:Angiotensin II; D000803:Angiotensin I; D002216:Captopril