Central Serotonin Depletion

Abstract

Serotonin (5-HT) in the central nervous system has been implicated in blood pressure control in both normotensive and hypertensive states. Parachlorophenylalanine (PCPA) depletes 5-HT in the central nervous system. Normotensive Wistar rats, Wistar rats made hypertensive by renal artery clipping (RHR), and spontaneously hypertensive rats (SHR) were depleted of central serotonin by the administration of PCPA. Mean arterial blood pressure (MAP), heart rate (HR), and plasma norepinephrine (NE) levels were measured in rats both before and after they were administered anesthesia with enflurane. Blood pressure was further decreased by the administration of saralasin, a competitive inhibitor of angiotensin II. Principal results are as follows. Central 5-HT was depleted by 70% or more with PCPA. In general, brain catecholamines were not altered by this treatment. No consistent pattern of change in MAP, HR, or plasma NE was observed for Wistar rats, RHR, or SHR during an awake control period in rats treated with PCPA compared with rats treated with vehicle. However, during enflurane anesthesia or enflurane anesthesia with saralasin, MAP, HR, and plasma NE were significantly greater in Wistar rats and RHR treated with PCPA compared to similar groups treated with vehicle. This was not observed in SHR: MAP, HR, and plasma NE were similar to vehicle-treated SHR. Nonsignificant changes in plasma epinephrine, plasma renin activity, or arterial blood gas tensions could not explain the differences seen in Wistar rats, RHR, or SHR. Central serotonin plays an important role in cardiovascular control during anesthesia with enflurane in Wistar rats but does not appear to play a dominant role in SHR.