The role of AT1 receptor-mediated reproductive function in renovascular hypertension in male rats

Abstract

There is an association between hypertension and reproductive dysfunction. Angiotensin II (Ang II) is involved in the pathogenesis of hypertension and the regulation of reproduction. The present study aimed to determine whether the angiotensinergic system mediates the effects of hypertension on reproductive function in male rats subjected to a two-kidney, one-clip (2K1C) model. Sexual behavior parameters, gametogenesis and plasma concentrations of Ang II, testosterone, prolactin and corticosterone were evaluated in male rats 28days after 2K1C or sham surgery and losartan (Los) treatment (a type 1 angiotensin II (AT1) receptor antagonist) or vehicle (V) treatment. The animals were divided into Sham+V, 2K1C+V, Sham+Los and 2K1C+Los groups. The 2K1C+V group showed a hypertensive response, inhibition of sexual behavior, spermatogenesis dysfunction, and increases in plasma Ang II and prolactin. Conversely, plasma testosterone decreased, and plasma corticosterone remained constant. Losartan treatment normalized blood pressure and prevented the changes in plasma testosterone and prolactin, sexual behavior and spermatogenesis in the 2K1C+Los group. In addition, losartan treatment caused an additional increase in circulating Ang ll in both groups (Sham+Los and 2K1C+Los). Together, these results suggest that Ang ll, acting through the AT1 receptor, modulates behavioral and endocrine parameters of reproductive function during renovascular hypertension. In addition, the effects of circulating Ang II on plasma testosterone and prolactin seem to contribute to the spermatogenic and sexual dysfunctions in hypertensive rats.

Reproductive Dysfunction in Female Rats With Renovascular Hypertension

“…15 Even less attention has been given to sexual dysfunction that may affect subjects with renovascular hypertension. Confirming studies in male rats, 11,12 the data presented here indicate that renovascular hypertension promotes an overall reduction in female reproductive function in rats. Specifically, 2K1C female rats show decreased oocyte numbers, sexual behavior, and LH levels during the proestrus afternoon when compared with control sham rats.…”

“…In the animal literature, only a few studies using the well-established rodent model of renovascular hypertension-the 2-kidney, 1-clip (2K1C) Goldblatt model 9,10 -have analyzed reproductive function in male rats, reporting a drastic impairment in reproductive functions. 11,12 Clinical data support the suggestion that sexual dysfunction is more frequent in women than in men. 13,14 Despite this higher prevalence, clinical and preclinical studies on female sexual dysfunction are remarkably scarce, and the mechanisms by which hypertension interferes with female reproductive function are still not fully understood.…”

“…A silver clip (0.15-mm internal diameter) was placed around the left renal artery though a flank incision. 11,12 The same surgical procedure was used for sham-operated rats, except for the placement of the renal artery clip.…”

“…Moreover, our results also corroborate other animal studies in which renovascular hypertensive male rats have shown sexual dysfunction. 11,12,28 The estradiol surge in proestrus is a required step to induce lordotic behavior. 29 However, 2K1C rats did not show any changes in estradiol levels in the proestrus afternoon, suggesting that the decreased sexual receptivity presented here is supported by other mechanisms.…”

Aliskiren Reduces the Adrenal Zona Glomerulosa Apoptosis and Autophagy in Wistar Rats with 2K1C Hypertension

“…Ang II can affect the expression of hormonal regulators of stress, such as corticosterone [ 46 ]. However, plasma corticosterone evaluated in rats induced to hypertension by the 2K1C model for 4 weeks showed no significant changes in the 2K1C group [ 47 ]. In another study, Müller et al [ 48 ] showed that there was no change in the basal level of corticosterone after systemic treatment of rats with exogenous angiotensin.…”