β-Adrenoceptor blockers are widely used to reduce heart rate, the strongest predictor of mortality in cardiac patients, but are less effective in diabetic patients. This study aimed to determine the specific β1 - and β2 -adrenoceptor subtype contributions to chronotropic responses in type 2 diabetes in vivo, which are currently unknown.
Type 2 diabetic and non-diabetic rats were implanted with radio-telemeters to measure arterial blood pressure and derive heart rate under conscious conditions. Vascular access ports were implanted to inject isoproterenol (β1 - and β2 -adrenoceptor agonist, 0.1-300 μg kg(-1) ) in the presence of atenolol (β1 -adrenoceptor antagonist, 2000 μg kg(-1) ) or nadolol (β1 - and β2 -adrenoceptor agonist, 4000 μg kg(-1) ) to determine β-adrenoceptor subtype chronotropic contributions.
Resting heart rate was reduced in diabetic rats (388 ± 62 vs. 290 ± 37 bpm non-diabetic vs. diabetic, P < 0.05, mean ± SD), which remained after atenolol or nadolol administration. Overall β-adrenoceptor chronotropic responsiveness was increased in diabetic rats (Δ heart rate at highest dose isoproterenol: 135 ± 66 vs. 205 ± 28 bpm, non-diabetic vs. diabetic, P < 0.05), a difference that diminished after β1 -adrenoceptor blockade with atenolol (Δ heart rate at highest dose isoproterenol: 205 ± 37 vs. 195 ± 22 bpm, non-diabetic vs. diabetic, P < 0.05).
The β1 -adrenoceptor is the main subtype to modulate chronotropic β-adrenoceptor responses in healthy, as well as diabetic rats. This study provides novel insights in the understanding of the pathological basis of dysregulation of heart rate in type 2 diabetes, which could be important for improving the current therapeutic strategies targeting the diabetic chronotropic incompetence. This article is protected by copyright. All rights reserved.
This research output has an Altmetric Attention Score of 15. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 26 June 2017.
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Altmetric has tracked 27,788,362 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 90th percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,130 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.7. This one has done particularly well, scoring higher than 93% of its peers.
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