Hemodynamic effects of β1‐ and β2‐adrenoceptor stimulation in conscious Zucker diabetic fatty rats (1155.7)

The β‐adrenoceptor (β‐AR) functional responsiveness and β 1 ‐AR expression, key components of blood pressure regulation, are reduced in many cardiomyopathies. Chronic heart failure in vitro models suggests that β 2 ‐AR redistribution might compensate for the decreased β 1 ‐AR function. Whether similar β‐AR subtype changes contribute to cardiovascular dysfunction in diabetes is unknown. Therefore, we aimed to determine the hemodynamic effects of specific β 1 ‐ and β 2 ‐AR stimulation in type II diabetes in vivo . Male Zucker Diabetic Fatty (ZDF) rats and paired lean littermates (20 week old n=8 per group) were implanted with a radiotelemeter and vascular access port to measure arterial blood pressure, derive heart rate (HR) and inject drugs intravenously under stress‐free conscious conditions. Cumulative doses of isoproterenol (non‐selective β 1 ‐ and β 2 ‐AR agonist, 0.001‐3µg/kg) or fenoterol (non‐selective β 2 ‐AR agonist, 0.001‐3µg/kg) in the presence of atenolol (selective β 1 ‐AR antagonist, 2000µg/kg) were injected. The increase in HR due to non‐selective β‐AR stimulation was not significantly different between ZDF and lean rats for all doses (at 0.1µg/kg: 106±10 vs. 109±13 bpm). However the HR response to specific β 2 ‐AR stimulation was significantly reduced in ZDF rats (25±4 vs. 2±4 bpm and 47±7 vs. 20±2 bpm; p<0.002 at 0.03 and 0.1µg/kg, respectively). Thus, in conscious diabetic ZDF rats the functional β‐AR responsiveness was not affected, whereas the sensitivity to specific β 2 ‐AR stimulation was reduced. Therefore, hemodynamic regulation by β 1 ‐ and β 2 ‐AR is altered in diabetes, and furthermore β 1 ‐AR signalling might play a compensatory role in maintaining β‐AR reactivity.