ANG II receptor blockade and arterial baroreflex regulation of renal nerve activity in cardiac failure

In cardiac failure, efferent renal sympathetic nerve activity (ERSNA) and the activity of the renin-angiotensin system are increased, and arterial baroreflex regulation of ERSNA is attenuated. We examined the effect of intravenous and intracerebroventricular angiotensin II AT₁ receptor blockade with losartan on the arterial baroreflex regulation of ERSNA in conscious control (C) and congestive heart failure (CHF) rats. Intravenous losartan (10 mg/kg, 21.7 μmol/kg) decreased arterial pressure more in CHF than in C rats (-28 ± 3 vs. -20 ± 3 mmHg, P < 0.05). After restoration of arterial pressure to the prelosartan value with methoxamine infusion, ERSNA was decreased more in CHF than in C rats (-23 ± 4 vs. -1 ± 2%, P < 0.05). Maximal gain of arterial baroreflex control of ERSNA (G(max)) was lower in CHF compared with C rats (-1.94 ± 0.10 vs. -3.78 ± 0.21%/mmHg, P < 0.05). Intravenous losartan increased G(max) in CHF (to -3.01 ± 0.14%/mmHg, P < 0.05) but not in C rats (to -3.56 ± 0.19%/mmHg). Intracerebroventricular losartan (4.61 μg, 10 nmol) did not affect arterial pressure but decreased ERSNA more in CHF than in C rats (-13 ± 2 vs. -8 ± 3%, P < 0.05). Like intravenous losartan, intracerebroventricular losartan increased G(max) in CHF (from -2.11 ± 0.18 to -3.21 ± 0.30%/mmHg, P < 0.05) but not in C rats (from -3.98 ± 0.25 to -3.84 ± 0.22%/mmHg). These results suggest that increased activity of the renin-angiotensin system contributes to the increase in ERSNA and its abnormal arterial baroreflex regulation in cardiac failure.