From the Klinik III für Innere Medizin der Universität zu
Köln, Köln (G.S., O.Z., U.L., M.B.), and the Institut für
Klinische Pharmakologie der Freien Universität Berlin,
Universitätsklinikum Benjamin Franklin, Berlin (M.P.), Germany.
Correspondence to Dr Gerhard Sitzler, Klinik III für Innere Medizin der Universität zu Köln, Joseph-Stelzmann-Straße 9, D-50924 Köln, Germany.
Abstract—In transgenic rats
harboring the mouse Ren-2d gene
[TG(mREN2)27], downregulation of the myocardial ß-adrenergic
receptor adenylyl cyclase system has been demonstrated previously.
Because a reduced vasodilatory reactivity may significantly contribute
to hypertension in this model of an activated tissue
renin-angiotensin system, the present study
investigated alterations of the vascular ß-adrenergic receptor
adenylyl cyclase system. In freshly harvested aortas from transgenic
rats, the activity of adenylyl cyclase was reduced significantly
(P<.05) in the presence of isoprenaline (10
µmol/L; -28±4.5%), guanosine 5'-triphosphate,
5'-guanylylimidodiphosphate [Gpp(NH)p] (100 µmol/L;
-29±4.7%), and forskolin (100 µmol/L) with (-42±6%) and
without (-40±4.3%) MnCl2. Densities of ß-adrenoceptors
were similar in both strains. In situ hybridization demonstrated the
expression of the transgene in aortic smooth muscle cells. These data
indicate a reduced catalyst function as a major contributing factor
involved in the maintenance of high blood pressure in
TG(mREN2)27. However, in cultivated aortic smooth muscle cells, cAMP
production after stimulation with isoprenaline, forskolin, and
Gpp(NH)p in the presence or absence of MnCl2 was not
different. Affinities and densities of ß-adrenoceptors and amounts of
immunochemically detected inhibitory and stimulatory
G-protein
© 1998 American Heart Association, Inc.
Scientific Contributions
Vascular ß-Adrenergic Receptor Adenylyl Cyclase System From Renin-Transgenic Hypertensive Rats
-subunits were unchanged. Desensitization after incubation
with 10 µmol/L isoprenaline for 72 hours was identical in smooth
muscle cells from both strains. Cell cultivation and isoprenaline
treatment had no effect on transgene expression. We concluded that in
transgenic rats the downregulation of the aortic ß-adrenergic
adenylyl cyclase system is due to humoral and
hemodynamic factors present in vivo rather than to
transgenicity itself.
Key Words: renin-angiotensin system • adenyl cyclase • receptors, adrenergic • muscle, smooth, vascular • rats, transgenic
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