Bombesin and substance P modulate peripheral sympathetic and cardiovascular activity

The vascular and cardiac effects of bombesin and substance P were evaluated in a "pithed rat preparation" in order to study the cardiovascular effects of these neuropeptides in the absence of the central nervous system control mechanisms. Bombesin (0.7, 7.0 and 70 nmol/kg) produced dose-dependent increases in mean arterial blood pressure (MAP): +6 +/- 1, +11 +/- 2 (p less than 0.05) and +22 +/- 2 mm Hg (p less than 0.01), respectively, when injected IV into the pithed rat. Heart rate (HR) responses to bombesin (0.7-70 nmol/kg) were also increased in a dose-dependent manner: +14 +/- 6, +28 +/- 5 (p less than 0.05) and +45 +/- 3 (p less than 0.05) beats/min (bpm), respectively. The blood pressure (BP) and HR responses to bombesin were diminished but not completely abolished by pretreatment with 1 mg/kg of either the beta-adrenergic receptor blocker propranolol or the H1-histamine receptor antagonist pyrilamine. Substance P similarly caused a dose-dependent increase in MAP: +7 +/- 1 and +38 +/- 7 mm Hg (p less than 0.001), by 0.7 and 700 nmol/kg, respectively, without altering HR. BP responses to sympathetic stimulation were also examined in the pithed rat utilizing electrical stimulation of the spinal cord (1 Hz, 50 V, 1 msec duration for 30 sec). These responses were potentiated by the low doses (0.7 and 7.0 nmol/kg) of bombesin (p less than 0.01) but tended to be suppressed by the highest dose. The HR response to stimulation was significantly reduced: -25 +/- 8 bpm (p less than 0.05) by the highest dose of bombesin (70 nmol/kg) but not with lower doses.(ABSTRACT TRUNCATED AT 250 WORDS)