Related Experiment Videos
Hyperglycaemia abolishes the antihypertrophic efficacy of bradykinin in rat ventricular myocytes
A C Rosenkranz1, G J Dusting, R H Ritchie
1Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville, Victoria, Australia.
Insights
High glucose levels in endothelial cells block bradykinin's ability to prevent heart cell hypertrophy. This finding impacts understanding of angiotensin-converting enzyme inhibitors and cardiovascular health.
Area of Science:
- Cardiovascular Biology
- Cellular Physiology
- Endocrinology
Background:
- Bradykinin normally inhibits cardiac myocyte hypertrophy.
- Endothelial cells are crucial for bradykinin's antihypertrophic effect.
- Hyperglycemia's impact on this interaction is not fully understood.
Purpose of the Study:
- To investigate how hyperglycemia affects bradykinin's ability to prevent cardiac myocyte hypertrophy.
- To examine the role of endothelial cells in this process under hyperglycemic conditions.
Main Methods:
- Adult rat ventricular myocytes were co-cultured with bovine aortic endothelial cells (BAEC).
- Hypertrophy was induced by angiotensin II (AngII) and measured by [3H]-phenylalanine incorporation.
- BAEC were pretreated with high glucose (25 mmol/L) to induce hyperglycemia before co-culture.
Main Results:
- Angiotensin II significantly increased myocyte hypertrophy, an effect abolished by bradykinin in normal co-cultures.
- Hyperglycemic pretreatment of BAEC reduced bradykinin's antihypertrophic effect.
- Hyperglycemia did not alter AngII's hypertrophic effect on myocytes.
Conclusions:
- Hyperglycemia in endothelial cells abolishes bradykinin's protective effect against cardiac myocyte hypertrophy.
- This suggests a mechanism by which high glucose impairs bradykinin signaling in the cardiovascular system.
- Findings have implications for the efficacy of angiotensin-converting enzyme inhibitors in diabetic patients.
Abstract:
1. Bradykinin inhibits hypertrophy of rat ventricular myocytes, but only in the presence of endothelial cells. 2. The influence of hyperglycaemia on the ability of bradykinin to prevent hypertrophy was investigated in adult rat ventricular myocytes cocultured with bovine aortic endothelial cells (BAEC). 3. In myocytes cocultured with normal BAEC, angiotensin II (AngII; 1 mumol/L) significantly increased [3H]-phenylalanine incorporation (an in vitro marker of hypertrophy) by 32 +/- 2%. This was abolished by bradykinin (10 mumol/L). 4. Pretreatment of BAEC with high glucose (25 mmol/L for 24 h) prior to coculture with myocytes reduced the antihypertrophic effect of bradykinin, but did not modulate the hypertrophic effect of AngII. 5. Pretreatment of BAEC with hyperglycaemia abolishes the antihypertrophic efficacy of bradykinin in rat ventricular myocytes cocultured with BAEC. This has implications for the action of angiotensin-converting enzyme inhibitors.