Comparison of verapamil and felodipine treatment on lipid and glucose metabolism in obese female SHHF/Mcc-fa(cp) rats

Calcium channel blockers, verapamil or felodipine, were given to geneticall y obese 6 and 11-month-old female SHHF/Mcc-fa(cp) (SHHF: Spontaneous Hypert ension Heart Failure) rats for 8 weeks to investigate their effects on gluc ose and lipid metabolism and obesity. Both antihypertensive agents signific antly decreased systolic blood pressure. In 11-month-old rats, verapamil tr eatment significantly decreased body weight after 4 weeks whereas with felo dipine it was only significantly reduced after 8 weeks. In 6-month-old rats , verapamil significantly curtailed body weight gain. Subcutaneous fat depo ts were smaller, and abdominal fat depots were larger in verapamil rats com pared to felodipine or control rats. Oral glucose tolerance tests in the 6- month-old verapamil and the 11-month-old felodipine groups showed improved glucose tolerance compared to their respective control groups. After 8 week s of treatment, fasting plasma glucose levels were lower in 6 month-old ver apamil rats compared to felodipine and control rats and were decreased by b oth verapamil and felodipine treatments as compared to control in 11-month- old rats. During the oral glucose tolerance test in 6-month-old rats, both fasting plasma insulin and the area under the insulin curve were increased in verapamil compared to both control and felodipine groups. When compared to controls, plasma cholesterol was increased by verapamil in both age grou ps, but was significantly decreased by felodipine after 8 weeks of treatmen t in the 11-month-old group. Plasma triglycerides increased in all control rats compared to initial levels; however, verapamil and felodipine groups s howed lower triglycerides in both age groups. In 6-month-old rats, the perc entages of plasma HDL significantly increased in both treatment groups as c ompared to control, This study shows that verapamil and felodipine depresse d body weight gain in the young rats, reduced body weight in the old rats, improved lipid parameters and glucose tolerance, but had the opposite effec ts on body fat distribution and insulin levels in obese female SHHF rats.