Abstract
Background The prevalence and severity of hypertension, as well as the activity of the systemic and local renin angiotensin systems (RASs), are gender related, with more symptoms in males than in females. However, the underlying mechanisms are not well understood. In this study, we investigated sex differences in renal vascular responses to angiotensin II (Ang II) administration with and without Ang II type 1 and Mas receptor (AT1R and MasR) antagonists (losartan and A779) in the 2K1C rat model of renovascular hypertension. Methods Male and female 2K1C rats were divided into 8 experimental groups (4 of each sex) treated with vehicle, losartan, A779, or A779+losartan. Responses of mean arterial pressure (MAP), renal blood flow (RBF), and renal vascular resistance (RVR) to Ang II were determined. Results In both sexes, the basal MAP, RBF, and RVR were not significantly different between the four groups during the control period. The Ang II administration decreased RBF and increased RVR in a dose-related manner in both sexes pretreated with vehicle or A779 (Pdose < 0.0001), but in vehicle pretreated groups, RBF and RVR responses were different between male and female rats (Pgroup < 0.05). AT1R blockade increased RBF and decreased RVR responses to Ang II, and no difference between the sexes was detected. Coblockades of AT1R and MasR receptors increased RBF response to Ang II significantly in males alone but not in females (Pgroup=0.04). Conclusion The impact of Ang II on RBF and RVR responses seems to be gender related with a greater effect on males, and this sex difference abolishes by Mas receptor blockade. However, the paradoxical role of dual losartan and A779 may provide the different receptor interaction in RAS between male and female rats.
Highlights
Hypertension is a complex condition which induces abnormalities such as left ventricular hypertrophy, carotid atherosclerosis, and renal dysfunction [1,2,3], and it is the leading modifiable risk factor for death [2, 4]
We examined the effects of blockade of the Ang II type 1 receptors (AT1R) and the Mas receptor (MasR) on the renal response to angiotensin II (Ang II) in male and female rats with 2K1C hypertension
The success rate of the accepted 2K1C hypertensive model was 32% in male and 31% in female rats. erefore, a total of 64 (30 males and 34 females) 2K1C rats were included in this study. e SYS pressure in male 2K1C rats was 157 ± 2.2 mmHg and in female 2K1C rats was 148.8 ± 2.1 mmHg which was significantly different P 0.023. ese data revealed less elevation of SYS pressure in female 2K1C rats compared with male 2K1C rats. e SYS blood pressure in male and female 2K1C groups was compared with the sham-operated group (Figure 2)
Summary
Hypertension is a complex condition which induces abnormalities such as left ventricular hypertrophy, carotid atherosclerosis, and renal dysfunction [1,2,3], and it is the leading modifiable risk factor for death [2, 4]. Is has been attributed in part to physiologic sex-based differences in the function of the renin angiotensin system (RAS) [6, 9,10,11]. Despite these apparent gender differences in human hypertension, similar treatment guidelines are applied in both males and females [8]. Erapeutic strategies targeting the RAS have differential effects, in males and females, on the complications of hypertension, including renal disease [12, 14, 16, 17]. Ang II type 1 receptor antagonists, as well as angiotensin-converting enzyme (ACE) and renin inhibitors, are widely used for treatment of hypertension [12,13,14,15]. erapeutic strategies targeting the RAS have differential effects, in males and females, on the complications of hypertension, including renal disease [12, 14, 16, 17]. e mechanisms that underlie these differences are incompletely defined
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