Cardiovascular responses induced by intrathecal substance P in the conscious freely moving rat

In conscious freely moving rats, administration of 0.65 to 32.5-nmol doses of substance P (SP) into the intrathecal (i.th.) space at the T8-T10 level of the spinal cord increased both mean arterial pressure (MAP) and heart rate (HR) in a dose-related manner. Concomitant with these cardiovascular effects, behavioral responses were observed. Injection of the peptide produced agitation of the rat for approximately 1 min as well as intermittent reciprocal hindlimb scratching which lasted for 3-6 min. The cardiovascular responses elicited by SP (6.5 nmol) were not blocked by systemic pretreatment with morphine (3-6 mg/kg), and the effect of SP on HR was potentiated by an i.th. dose of morphine (10 micrograms) given prior to the injection of SP. A systemic dose of phentolamine (1 mg/kg) blocked the pressor response and a depressor effect appeared, whereas propranolol (1 mg/kg) blocked the HR response. Although catecholamines mediate the spinal action of SP on MAP and HR, bilateral adrenalectomy of the rat 48 h prior to experimentation failed to affect the cardiovascular responses to SP. After transection of the spinal cord at the C3-C4 level, the hindlimb scratching behavior and the pressor response to SP were unaffected but the peak HR response was significantly reduced. These results demonstrate that the rise in MAP and HR evoked by SP is not secondary to perception of a noxious stimulus by the rat and that adrenal medullary catecholamines are not essential for these cardiovascular effects.(ABSTRACT TRUNCATED AT 250 WORDS)