Use of ganglionic blockers to assess neurogenic pressor activity in conscious rats

The present study was conducted to develop a standardized ganglionic blockade protocol to assess neurogenic pressor activity in conscious rats. Rats were instrumented with arterial and venous catheters for measurement of arterial pressure and heart rate and for administration of three different ganglionic blockers (trimethaphan, hexamethonium, and chlorisondamine). To investigate the role of the pressor hormones angiotensin II (AII) and arginine vasopressin (AVP) in modulating the cardiovascular responses to ganglionic blockade, we also administered ganglionic blockers to rats pretreated with AVP and AII receptor antagonists. The peak depressor responses to trimethaphan (20 mg/kg; -45 +/- 2 mm Hg), hexamethonium (20 mg/kg; -44 +/- 2 mm Hg), and chlorisondamine (2.5 mg/kg; -47 +/- 3 mm Hg) were not different from each other. With trimethaphan, there was a significantly enhanced peak depressor response after blockade of AT1/V1 receptors (-45 +/- 2 vs -59 +/- 2 mm Hg). No significant differences were observed for hexamethonium or chlorisondamine after hormonal blockade (-44 +/- 2 vs. -46 +/- 3 and -47 +/- 3 vs -48 +/- 4 mm Hg, respectively). These observations suggest that, for hexamethonium and chlorisondamine, the peak depressor response to ganglionic blockade is a consistent measure of neurogenic pressor activity in the conscious rat. This response is not influenced by circulating AII or AVP. On the other hand, trimethaphan should be used carefully due to its complex interactions with other systems, particularly under conditions in which AVP or AII may be altered.