Prevention of metabolic disorders and reproductive performance deficits by the blockade of Angiotensin II AT1 receptor in female rats fed with cafeteria diet

Abstract Besides the well-known detrimental effects of obesity on cardiovascular and metabolic function, studies have shown that obesity is also associated with impaired reproductive function in women. Alterations in Angiotensin II (Ang II) have been associated with obesity and with female reproduction. The aim of the present study was to evaluate the reproductive and metabolic effects of Ang II AT1 receptor blockade with losartan in an animal model of obesity, in which female rats were offered a palatable, high calorie diet from weaning to adulthood. Sexual behavior, ovulation rates and preovulatory levels of the hormones estradiol, progesterone, LH and prolactin were analyzed. Retroperitoneal and perigonadal fat pads, triglycerides and cholesterol (total, HDL and LDL), and insulin resistance were analyzed. Losartan prevented increases in fat pad storage, insulin resistance, as well as triglycerides and LDL levels induced by cafeteria diet intake. Losartan also prevented ovulatory deficits and loss of preovulatory surges of progesterone and LH in cafeteria-fed female rats probably through the prevention of the increase in body weight and body fat. No alterations in sexual behavior were observed. These results suggest, for the first time, that Ang II contributes to the development of the deleterious effects of obesity on preovulatory surges of LH and progesterone and on the reduction of ovulation in obese female rats.