Development of renovascular hypertension after central serotonin depletion.

Abstract

The participation of the central serotonergic system in the development of two-kidney, two clip (2K2C) Goldblatt renovascular hypertension in the rat has been examined. Half of the rats were treated with desmethylimipramine intraperitoneally and 5,7-dihydroxytryptamine intracisternally; the other half received only desmethylimipramine and the 5,7-dihydroxytryptamine vehicle. Two days later, a silver clip was placed in both renal arteries in half of the rats of each group. A sham operation was performed in the remaining rats. Blood pressure was recorded during the 5 weeks after treatment. At the end of the experiment, blood and cerebrospinal fluid samples were obtained. The brain was dissected into several areas and kept frozen. Norepinephrine, serotonin, angiotensinogen, and renin-like concentration were evaluated in the brain areas. Plasma renin activity and angiotensinogen concentration in the plasma and cerebrospinal fluid were estimated. In the sham-operated groups, blood pressure was lower in the treated than in the control rats. The curve of blood pressure increase, as well as the final blood pressure, was similar in the treated and control 2K2C rats. Serotonin was significantly depleted by the 5,7-dihydroxytryptamine treatment in all brain areas. Treatment did not induce any changes in central norepinephrine concentration. Plasma renin activity was diminished in the treated sham-operated rats. These data indicate that the central serotonin depletion does not prevent the development of hypertension and confirm the role of the amine in normal blood pressure regulation. On the other hand, the peripheral renin-angiotensin system might participate in the development of high blood pressure in serotonin-depleted animals.