The Central and Peripheral Renin-Angiotensin System in Reserpine-Treated Rats

In a previous work we observed that intracerebroventricularly administered 6-hydroxydopamine produced an almost complete depletion of central norepinephrine and, at the same time, caused significant changes in angiotensinogen concentration in the cerebrospinal fluid and brain parenchyma without inducing any changes in the peripheral norepinephrine content or in the reninangiotensin system. The purpose of the present study was to determine whether these changes were due to norepinephrine depletion or solely to the administration of 6-hydroxydopamine. Norepinephrine depletion was induced by peripheral reserpine treatment. Male Wistar rats were divided into four groups. In Group 1,10 rats received reserpine (10 mg/kg i.p.) and were killed 48 hours later. In Group 2, a control group, 8 rats received the vehicle. In Group 3,10 rats received daily doses of reserpine (5 mg/kg i.p.) and were killed 8 days later. In Group 4, also a control group, 9 rats received the vehicle. Blood and cerebrospinal fluid samples were collected; the brain was then extracted and dissected into several areas. The mesenteric arteries and the adrenal glands were also excised. Plasma renin activity, plasma angiotensinogen concentration, and renin and angiotensinogen concentrations in the brain areas were evaluated. Norepinephrine concentration was determined in all the tissues. The animals in Group 1 showed a decrease hi plasma renin activity; norepinephrine was partially depleted in the brain areas, and angiotensinogen concentration was increased in the brainstem. In Group 3 rats, norepinephrine was drastically depleted in the brain and peripheral tissues. Plasma renin activity was increased, whereas angiotensinogen concentration was decreased in plasma, cerebrospinal fluid, and hypothalamus and increased in brainstem and cerebellum. Renin concentration was increased in the hypothalamus. These results indicate that noradrenergic depletion due to peripheral or central sympathectomy is able to induce significant changes in the peripheral or central renin-angiotensin system.