Cardiovascular interactions between losartan and fructose in mice.
OBJECTIVE
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.
Senador
Danielle
D
Wright State University, Boonshoft School of Medicine, Dayton, OH 45435, USA. mariana.morris@wright.edu
Key
Mary
M
Brosnihan
K Bridget
KB
Irigoyen
Maria Claudia
MC
Elased
Khalid M
KM
Morris
Mariana
M
D000704:Analysis of Variance; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects*; D002784:Cholesterol / Q000097:blood; D004195:Disease Models, Animal; D004347:Drug Interactions; D005632:Fructose / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D007328:Insulin / Q000097:blood; D007668:Kidney / Q000378:metabolism; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*
D000959:Antihypertensive Agents; D007328:Insulin; D044140:Receptor, Angiotensin, Type 1; D005632:Fructose; D002784:Cholesterol; D007703:Peptidyl-Dipeptidase A; D019808:Losartan