Alterations in atrial reactivity in a strain of spontaneously diabetic rats.
1. The present study examined the reactivity of atria from control and spontaneously diabetic rats to various adrenoceptor agonists and to adenosine. 2. Isoprenaline (1.5 nM-1500 nM) produced concentration-dependent increases in inotropy which were unchanged in diabetic atria. However, the sensitivity to isoprenaline-induced changes in chronotropy was reduced in diabetic preparations. 3. In the presence of propranolol (2 microM), phenylephrine (0.2 microM-100 microM) produced concentration-dependent increases in both inotropy and chronotropy; however, atria from diabetic rats exhibited a much greater maximal response. The diabetic state did not alter the sensitivity to phenylephrine. 4. Adenosine (0.15 microM-300 microM) produced concentration-dependent decreases in both inotropy and chronotropy which were unchanged in diabetic atria. 5. Radioligand binding studies revealed that both alpha 1- and beta-adrenoceptor populations were substantially reduced in atria from diabetic rats. However, there was no change in receptor affinity for either adrenoceptor. 6. These results show that diabetes leads to an alteration in atrial reactivity to adrenoceptor stimulation. Future studies examining steps following hormone-receptor coupling are required in order to characterize this defect.
Durante
W
W
Department of Pharmacology, University of Toronto, Ontario, Canada.
Sunahara
F A
FA
Sen
A K
AK
D000241:Adenosine / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D006325:Heart Atria / Q000187:drug effects / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012794:Sialic Acids / Q000378:metabolism
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D012794:Sialic Acids; D000241:Adenosine