Cardiovascular interactions between losartan and fructose in mice
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Published on: September 17, 2015
Danielle Senador1, Mary Key, K Bridget Brosnihan
1Wright State University, Boonshoft School of Medicine, Dayton, OH 45435, USA. mariana.morris@wright.edu
Aim:
To determine whether pharmacological blockade of angiotensin (Ang) AT1 receptors alters the cardiovascular, metabolic, and angiotensin-converting enzyme (ACE and ACE2) responses to a fructose diet in mice.
Methods:
C57BL male mice were fed with a 60% fructose diet for 8 weeks in combination with losartan treatment on week 9 (30 mg/kg per day). Blood pressure (BP), heart rate (HR), and autonomic balance were monitored using radiotelemetry with spectral analysis. Renal ACE and ACE2 activity and protein levels as well as Ang II and Ang 1-7 were measured.
Results:
Fructose impaired glucose tolerance and increased plasma cholesterol and insulin. These effects were not corrected by losartan treatment. Fructose increased BP and HR but only during the dark period. Short-term losartan treatment decreased BP by 16% in the fructose group but had no effect in controls. This was accompanied by a decrease in BP variance and its low-frequency component. Fructose increased Ang II (plasma and kidney) and ACE 2 (renal activity and protein expression). Losartan alone increased plasma Ang II in plasma and ACE2 in kidney. There were no changes in renal Ang 1-7 levels.
Conclusions:
Losartan reversed the pressor effect of a high fructose diet, demonstrating that there are prominent interactions between a dietary regimen that produces glucose intolerance and an antihypertensive drug that antagonizes Ang signaling. The mechanism of change may be via renal Ang II rather than the ACE2/Ang 1-7 pathway because the fructose losartan combination resulted in lowered renal Ang II without changes in Ang 1-7.
Insights
Losartan treatment reversed high fructose diet-induced high blood pressure in mice. This highlights interactions between diet, glucose intolerance, and angiotensin receptor blockers, potentially via renal Angiotensin II.
Area of Science:
- Cardiovascular physiology
- Metabolic research
- Renal function
Background:
- High fructose diets can induce metabolic disturbances and cardiovascular changes.
- The renin-angiotensin system plays a crucial role in regulating blood pressure and cardiovascular homeostasis.
- Angiotensin-converting enzyme 2 (ACE2) and its product Angiotensin 1-7 (Ang 1-7) are involved in counter-regulating the effects of Angiotensin II (Ang II).
Purpose of the Study:
- To investigate the impact of losartan, an angiotensin (Ang) AT1 receptor blocker, on cardiovascular and metabolic responses to a high fructose diet in mice.
- To examine the effects on the angiotensin-converting enzyme (ACE) and ACE2 pathways.
Main Methods:
- Male C57BL mice were fed a 60% fructose diet for 8 weeks.
- Losartan (30 mg/kg/day) was administered during week 9.
- Cardiovascular parameters (blood pressure, heart rate) were monitored via radiotelemetry.
- Renal ACE and ACE2 activity, protein levels, and Ang II and Ang 1-7 levels were measured.
Main Results:
- Fructose diet impaired glucose tolerance and increased cholesterol and insulin, effects not mitigated by losartan.
- Fructose increased blood pressure and heart rate during the dark period.
- Losartan treatment significantly reduced blood pressure in fructose-fed mice.
- Fructose increased renal and plasma Ang II and renal ACE2 activity; losartan alone increased plasma Ang II and renal ACE2.
- Renal Ang 1-7 levels remained unchanged.
Conclusions:
- Losartan effectively reversed the pressor effects of a high fructose diet in mice.
- This suggests significant interactions between fructose-induced metabolic changes and Angiotensin signaling.
- The mechanism appears to involve modulation of renal Ang II, rather than the ACE2/Ang 1-7 pathway.
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