Endothelial cell‐targeted over‐expressing ET‐1 leads to increased blood pressure and decreased heart rate in aged mice (LB655)

Abstract

Endothelin‐1 (ET‐1) is a 21 amino acid vasoconstrictor and implicated in the regulation of hypertention. Recently, our colleagues found that transgenic mice (TET‐1) with endothelial ET‐1 over‐expression developed hypertention in young mice by changing vascular properties. However, the effects of over‐expressing endothelial ET‐1 on cardiovascular system in aged mice are still unclear. Therefore, this study investigated the blood pressure and heart rate of TET‐1 aged mice and non‐transgenic (NTg) aged mice (1.5‐2 years old). A non‐invasive tail cuff measurement showed that a significant elevation of both systolic (115.1 ± 2.935 vs 103.5 ± 1.846 mmHg, p<0.01) and diastolic (85.81 ± 2.303 vs 74.56 ± 2.029 mmHg, p<0.05) in conscious TET‐1 aged mice comparing to NTg counterpart, indicating over‐expressed endothelial ET‐1 cause both systolic and diastolic hypertension in aged mice. And, aged TET‐1 mice showed a significantly decreased heart rate to aged NTg mice (616.7 ± 20.14 vs 670.9 ± 11.57 beats per minute (bpm), p<0.05). Moreover, Rate‐pressure product is a sensitive index of myocardial oxygen consumption, and it was not altered in TET‐1 mice (71085 ± 3258 vs 69337 ± 1233 bpm*mmHg, p>0.05), implicating over‐expressed endothelial ET‐1 would change cardiovascular properties by mechanisms of mutual compensation between blood pressure and heart rate. These findings provide evidence for roles of endothelial ET‐1 in altering cardiovascular system in aged mice. This study also implicates clinical importance of endothelial ET‐1 as a therapeutic target for hypertension in the elderly.Grant Funding Source: Supported by the departmental fund, Department of Anaesthesiology, The University of Hong Kong