0000000000230946
AUTHOR
Rudi Busse
ACE inhibitor potentiation of bradykinin-induced venoconstriction
1. Angiotensin-converting enzyme (ACE) inhibitors exert their cardiovascular effects not only by preventing the formation of angiotensin II (AII), but also by promoting the accumulation of bradykinin in or at the vessel wall. In addition, certain ACE inhibitors have been shown to augment the vasodilator response to bradykinin, presumably by an interaction at the level of the B2 receptor. We have investigated whether this is a specific effect of the ACE inhibitor class of compounds in isolated endothelium-denuded segments of the rabbit jugular vein where bradykinin elicits a constrictor response which is exclusively mediated by activation of the B2 receptor. 2. Moexiprilat and ramiprilat (< …
Angiotensin-Converting Enzyme Inhibitor Ramiprilat Interferes With the Sequestration of the B 2 Kinin Receptor Within the Plasma Membrane of Native Endothelial Cells
Background —ACE (kininase II) inhibitors have been shown to exert their beneficial cardiovascular effects via the inhibition of both angiotensin II formation and bradykinin breakdown. Because recent evidence suggests that ACE inhibitors may also interfere with B 2 kinin receptor signaling and thus enhance the vascular response to bradykinin, we examined whether the distribution of B 2 kinin receptors within the plasma membrane of native endothelial cells is affected by an ACE inhibitor. Methods and Results —Localization of the B 2 kinin receptor in membranes prepared from native porcine aortic endothelial cells was evaluated by means of specific [ 3 H]bradykinin binding and immunoprecipita…
Subcellular localization and characterization of nitric oxide synthase(s) in endothelial cells: physiological implications.
Endothelial cells (EC) contain a constitutive Ca2+/calmodulin-dependent nitric oxide (NO) synthase (cNOS) which plays an important role in the local control of vascular tone. We compared the subcellular distribution of this enzyme in cultured and freshly isolated pig EC by determination of specific cNOS activity and immunoblot analysis. Similar studies were also performed with cultured and freshly isolated bovine and cultured human EC. Enzyme activity was predominantly (&gt; 70%) associated with the particulate fraction of all EC types tested and was highest in freshly isolated porcine EC. Both specific cNOS activity and immunoreactivity were substantially higher (&gt; 3-fold) in th…