%0 Journal Article %1 Bohm1988 %A Bohm, M. %A Beuckelmann, D. %A Diet, F. %A Feiler, G. %A Lohse, M. J. %A Erdmann, E. %D 1988 %J Naunyn Schmiedebergs Arch Pharmacol %K Aging/physiology Animals Cardiomegaly/physiopathology Contraction/drug Electric Hypertension/*metabolism Isoproterenol/pharmacology Male Muscle Muscles/physiology Myocardium/*metabolism Papillary Phenylephrine/pharmacology Rats SHR Stimulation WKY alpha/*drug beta/*drug effects Receptor Mice Adrenergic %N 4 %P 383-91 %T Properties of cardiac alpha- and beta-adrenoceptors in spontaneously hypertensive rats %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2854206 %V 338 %X The effects of isoprenaline, Ca2+ and phenylephrine (in the presence of propranolol) on force of contraction were studied in isolated electrically driven papillary muscles of spontaneously hypertensive rats (SHR) and age-matched (14-18 weeks) Wistar Kyoto control rats (WK). Cardiac alpha- and beta-adrenoceptors were characterized by radioligand binding studies. The positive inotropic effect of isoprenaline in SHR was less effective than in control rats. The EC50 values did not differ in both groups. In SHR, isoprenaline was less effective than Ca2+ to increase force of contraction whereas in WK it had the same effectiveness as Ca2+. The positive inotropic effect of phenylephrine in the presence of propranolol was similar in SHR and WK. In SHR, both the densities of cardiac alpha- and beta-adrenoceptors were reduced. In beta-adrenoceptor binding experiments, the nonhydrolysable GTP analog Gpp(NH)p caused a rightward shift of agonist competition curves of isoprenaline. Biphasic competition curves revealed a similar percentage of low and high affinity sites in SHR and WK, respectively. In alpha-adrenoceptor binding experiments, Gpp(NH)p caused no detectable shift of agonist competition curves with norepinephrine. It is suggested that cardiac beta-adrenoceptor down-regulation is involved in the reduced positive inotropic effect of isoprenaline in SHR. Functional uncoupling of beta-adrenoceptors does not appear to be involved in the reduced beta-adrenoceptor-mediated positive inotropism in SHR. Binding studies do not show evidence for a large number of alpha-adrenoceptors coupling to a guanine-nucleotide binding protein in the rat heart. Finally, in ventricular myocardium of SHR, cardiac alpha-adrenoceptors do not serve as a reserve mechanism during impaired beta-adrenergic stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

@article{Bohm1988, abstract = {The effects of isoprenaline, Ca2+ and phenylephrine (in the presence of propranolol) on force of contraction were studied in isolated electrically driven papillary muscles of spontaneously hypertensive rats (SHR) and age-matched (14-18 weeks) Wistar Kyoto control rats (WK). Cardiac alpha- and beta-adrenoceptors were characterized by radioligand binding studies. The positive inotropic effect of isoprenaline in SHR was less effective than in control rats. The EC50 values did not differ in both groups. In SHR, isoprenaline was less effective than Ca2+ to increase force of contraction whereas in WK it had the same effectiveness as Ca2+. The positive inotropic effect of phenylephrine in the presence of propranolol was similar in SHR and WK. In SHR, both the densities of cardiac alpha- and beta-adrenoceptors were reduced. In beta-adrenoceptor binding experiments, the nonhydrolysable GTP analog Gpp(NH)p caused a rightward shift of agonist competition curves of isoprenaline. Biphasic competition curves revealed a similar percentage of low and high affinity sites in SHR and WK, respectively. In alpha-adrenoceptor binding experiments, Gpp(NH)p caused no detectable shift of agonist competition curves with norepinephrine. It is suggested that cardiac beta-adrenoceptor down-regulation is involved in the reduced positive inotropic effect of isoprenaline in SHR. Functional uncoupling of beta-adrenoceptors does not appear to be involved in the reduced beta-adrenoceptor-mediated positive inotropism in SHR. Binding studies do not show evidence for a large number of alpha-adrenoceptors coupling to a guanine-nucleotide binding protein in the rat heart. Finally, in ventricular myocardium of SHR, cardiac alpha-adrenoceptors do not serve as a reserve mechanism during impaired beta-adrenergic stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)}, added-at = {2010-12-14T18:12:02.000+0100}, author = {Bohm, M. and Beuckelmann, D. and Diet, F. and Feiler, G. and Lohse, M. J. and Erdmann, E.}, biburl = {https://www.bibsonomy.org/bibtex/2986d86546d2474f003e0d1959d809c64/pharmawuerz}, endnotereftype = {Journal Article}, interhash = {396597211b14fe366a53a4a1f930c28e}, intrahash = {986d86546d2474f003e0d1959d809c64}, issn = {0028-1298 (Print) 0028-1298 (Linking)}, journal = {Naunyn Schmiedebergs Arch Pharmacol}, keywords = {Aging/physiology Animals Cardiomegaly/physiopathology Contraction/drug Electric Hypertension/*metabolism Isoproterenol/pharmacology Male Muscle Muscles/physiology Myocardium/*metabolism Papillary Phenylephrine/pharmacology Rats SHR Stimulation WKY alpha/*drug beta/*drug effects Receptor Mice Adrenergic}, month = Oct, note = {Bohm, M Beuckelmann, D Diet, F Feiler, G Lohse, M J Erdmann, E In Vitro Research Support, Non-U.S. Gov't Germany, west Naunyn-Schmiedeberg's archives of pharmacology Naunyn Schmiedebergs Arch Pharmacol. 1988 Oct;338(4):383-91.}, number = 4, pages = {383-91}, shorttitle = {Properties of cardiac alpha- and beta-adrenoceptors in spontaneously hypertensive rats}, timestamp = {2010-12-14T18:22:55.000+0100}, title = {Properties of cardiac alpha- and beta-adrenoceptors in spontaneously hypertensive rats}, url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2854206}, volume = 338, year = 1988 }