Diabetes reduces right atrial beta-adrenergic signaling but not agonist stimulation of heart rate in swine

This study assessed the effects of streptozotocin diabetes in swine on the heart rate response to beta -adrenergic stimulation the adenylyl cyclase si gnal transduction pathway. Diabetic animals (n = 9) were hyperglycemic comp ared to the control group (n = 10) (12.6 +/- 1.0 vs. 3.53 +/- 0.29 mM). The re were no significant differences between the diabetic and nondiabetic gro ups in the heart rate response to isoproterenol, however, there was a signi ficant reduction (14%) in beta -adrenergic receptor density in the right at rium in the diabetic (61 +/- 3 fmol/mg protein) versus the nondiabetic grou p (71 +/- 3) (P < 0.05). The content of guanosine triphosphate binding regu latory proteins (Gs and Gi) in the right atrium was not affected by diabete s, nor was adenylyl cyclase activity under unstimulated conditions or with receptor-dependent stimulation with isoproterenol. On the other hand, adeny lyl cyclase activity was 34% lower when directly stimulated with forskolin, and it was reduced by 23% when stimulated through Gs with Gpp(NH)p. In con clusion, beta-adrenergic stimulation of heart rate with isoproteronol and t he receptor-dependent signal transduction pathway remained intact in the ri ght atrium of diabetic swine despite reduced beta-adrenergic receptor densi ty, G-protein content, and direct stimulation of adenylyl cyclase activity.