Abstract
Renovascular hypertension is a type of secondary hypertension caused by renal artery stenosis, leading to an increase in the renin–angiotensin–aldosterone system (RAAS). Two-kidney, 1-clip (2K1C) is a model of renovascular hypertension in which rats have an increased sodium intake induced by water deprivation (WD), a common situation found in the nature. In addition, a high-sodium diet in 2K1C rats induces glomerular lesion. Therefore, the purpose of this study was to investigate whether angiotensin II (ANG II) and/or aldosterone participates in the increased sodium intake in 2K1C rats under WD. In addition, we also verified if central AT1 and mineralocorticoid receptor blockade would change the high levels of arterial pressure in water-replete (WR) and WD 2K1C rats, because blood pressure changes can facilitate or inhibit water and sodium intake. Finally, possible central areas activated during WD or WD followed by partial rehydration (PR) in 2K1C rats were also investigated. Male Holtzman rats (150–180 g) received a silver clip around the left renal artery to induce renovascular hypertension. Six weeks after renal surgery, a stainless-steel cannula was implanted in the lateral ventricle, followed by 5–7 days of recovery before starting tests. Losartan (AT1 receptor antagonist) injected intracerebroventricularly attenuated water intake during the thirst test. Either icv losartan or RU28318 (mineralocorticoid receptor antagonist) reduced 0.3 M NaCl intake, whereas the combination of losartan and RU28318 icv totally blocked 0.3 M NaCl intake induced by WD in 2K1C rats. Losartan and RU28318 icv did not change hypertension levels of normohydrated 2K1C rats, but reduced the increase in mean arterial pressure (MAP) produced by WD. c-Fos expression increased in the lamina terminalis and in the NTS in WD condition, and increased even more after WD-PR. These results suggest the participation of ANG II and aldosterone acting centrally in the enhanced sodium intake in WD 2K1C rats, and not in the maintenance of hypertension in satiated and fluid-replete 2K1C rats.
Highlights
Renovascular hypertension is a type of secondary hypertension caused mainly by atherosclerotic renal artery stenosis, followed by fibromuscular disease, arteritis, thrombosis, arterial dissection, and stenosis in a transplanted kidney [reviewed in (Derkx and Schalekamp, 1994; Textor, 2017; Herrmann and Textor, 2018)], and account for approximately 5–6% of high blood pressure cases in the elderly (Hansen et al, 2002)
After 24 h of Water deprivation (WD), 2K1C rats ingested significant amount of water compared to WR 2K1C rats (16.4 ± 1.5, vs. WR: 1.2 ± 0.4 ml/2 h; p < 0.05), a response reduced by the pretreatment with losartan (66 μg/1 μL) into the lateral ventricle (LV) (9.8 ± 1.8 ml/2 h) [F (3, 21) 26.17; p < 0.05], Figure 2
During the salt appetite test, WD 2K1C rats ingested significant amount of 0.3 M NaCl intake compared to WR 2K1C (7.5 ± 2.9, vs WR: 1.2 ± 0.4 ml/2 h), a response reduced by the pretreatment with losartan into the LV (3.6 ± 1.3 ml/2 h) [F (3, 21) 6.35; p < 0.05], Figure 2
Summary
Renovascular hypertension is a type of secondary hypertension caused mainly by atherosclerotic renal artery stenosis, followed by fibromuscular disease, arteritis, thrombosis, arterial dissection, and stenosis in a transplanted kidney [reviewed in (Derkx and Schalekamp, 1994; Textor, 2017; Herrmann and Textor, 2018)], and account for approximately 5–6% of high blood pressure cases in the elderly (Hansen et al, 2002). The increase in renin–angiotensin–aldosterone system (RAAS) activity has a pivotal role in the development of renovascular hypertension (Leenen et al, 1975; Lincevicius et al, 2015; Textor, 2017; Roncari et al, 2018). The central or peripheral administration of AT1 receptor or aldosterone receptor antagonist was efficient in decreasing the high blood pressure levels of renovascular hypertension similar to that in 2-kidney-1clip (2K1C) rats (Wilcox et al, 1996; de Oliveira-Sales et al, 2010; Lincevicius et al, 2015; Boshra and Abbas, 2017). 2K1C rats display an increased daily sodium intake (Mohring et al, 1975; Roncari et al, 2018). Water conservation and sodium excretion by the kidneys, and thirst and sodium appetite, two motivated behavior states induced by WD, arise as responses to WD-induced hypovolemia and hyperosmolality (Weisinger et al, 1985; Sato et al, 1996; De Luca Jr et al, 2002; McKinley and Johnson, 2004; Bourque, 2008)
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