AT(1) receptor blockers prevent sympathetic hyperactivity and hypertensionby chronic ouabain and hypertonic saline

Sympathetic hyperactivity and hypertension caused by chronic treatment with ouabain or sodium-rich artificial cerebrospinal fluid (aCSF) can be preven ted by central administration of an angiotensin type 1 (AT(1)) receptor blo cker. In the present study, we assessed whether, in Wistar rats, chronic pe ripheral treatment with the AT(1) receptor blockers losartan and embusartan can exert sufficient central effects to prevent these central effects of o uabain and sodium. Losartan or embusartan (both at 100 mg . kg(-1) . day(-1 )) were given subcutaneously once daily. Ouabain (50 mug/day) was infused s ubcutaneously, and sodium-rich aCSF (1.2 M Na+, 5 mul/h) was infused intrac erebroventricularly, both by osmotic minipump for 13-14 days. The mean arte rial pressure (MAP) at rest and in response to air stress and intracerebrov entricularly injection of guanabenz (75 mug/7.5 mul), ANG II (30 ng/3 mul), and ouabain (0.5 mug/2 mul) were then measured. In control rats, chronic t reatment with ouabain subcutaneously and hypertonic saline intracerebrovent ricularly both increased baseline MAP by 20-25 mmHg and enhanced twofold th e pressor responses to air stress and depressor responses to the alpha (2)- adrenoceptor agonist guanabenz. Simultaneous treatment with losartan or emb usartan fully prevented hypertension, maintained normal responses to air st ress and guanabenz, and attenuated pressor responses to acute intracerebrov entricular injection of ANG II and ouabain. We concluded that peripheral ad ministration of losartan as well as embusartan can cause sufficient central effects to prevent the sympathetic hyperactivity and hypertension induced by chronic peripheral ouabain and central sodium.