title: β3-Adrenoceptor-mediated responses in diabetic rat heart.
abstract: β3-adrenoceptors mediate negative inotropic effect in contrast to classical β1- and β2-adrenoceptors. Cardiac β3-adrenoceptors are upregulated in experimental diabetes. Thus, cardiodepressant effect mediated by β3-adrenoceptors has been proposed to contribute to the impaired cardiac function in this pathology. In our study, we investigated the influence of streptozotocin-diabetes on cardiac contractility to β3-adrenoceptors stimulation by using Langendorff-perfused rat hearts. BRL 37344, a selective β3-adrenoceptor agonist, induced dose-dependent decreases in left ventricular developed pressure (LVDP) in hearts from control rats. BRL 37344 also dose-dependently decreased +dP/dt and -dP/dt values. Effects of BRL 37344 were abolished by SR 59230, but not altered by nadolol pre-treatment. On the other hand, these effects of BRL 37344 were all significantly increased in hearts from diabetic rats. We also observed that diabetes significantly increased the mRNA levels encoding cardiac β3-adrenoceptors. In addition, Giα2 mRNA expressions were found to be increased in the cardiac tissue of diabetic rats as well. The effect of BRL 37344 on cardiac contractility was normalized upon treatment of diabetic rats with insulin. These data demonstrate an increased effect of β3-adrenoceptor stimulation on hemodynamic function of the heart in accordance with an increased mRNA levels encoding cardiac β3-adrenoceptors in 8-week diabetic rats.
authors: Department of Pharmacology, Faculty of Pharmacy, Ankara University, 06100, Tandogan, Ankara, Turkey. gkayki@ankara.edu.tr.
authors: Gizem
authors: G
authors: Kayki-Mutlu
authors: Ebru
authors: E
authors: Arioglu-Inan
authors: Isil
authors: I
authors: Ozakca
authors: Arif T
authors: AT
authors: Ozcelikay
authors: Vecdi M
authors: VM
authors: Altan
mesh_terms: D058673:Adrenergic beta-3 Receptor Antagonists / Q000737:chemistry; D000318:Adrenergic beta-Agonists / Q000737:chemistry; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004983:Ethanolamines / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics; D007328:Insulin / Q000627:therapeutic use; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism*; D011412:Propanolamines / Q000737:chemistry; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D022702:Receptors, Adrenergic, beta-3 / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C097869:3-(2-ethylphenoxy)-1-(1,2,3,4-tetrahydronaphth-1-ylamino)-2-propanol oxalate; D058673:Adrenergic beta-3 Receptor Antagonists; D000318:Adrenergic beta-Agonists; D004983:Ethanolamines; D007328:Insulin; D011412:Propanolamines; D012333:RNA, Messenger; D022702:Receptors, Adrenergic, beta-3; C057368:BRL 37344