Substance P given intrathecally at the spinal T 9 level increases arterial pressure and heart rate in the rat

Abstract

Administration of 10 μg of substance P intrathecally at the spinal T 9 level of the unanaesthetized and the anaesthetized rat provoked an increase in arterial pressure and an increase in heart rate. Both cardiovascular responses began within 1–2 min of administration, and the peak of each occurred at 4–10 min. In the anaesthetized rat, which gave rise to the bulk of the responses reported, peak arterial pressure was ca 20 mm Hg greater than pre-administration levels, and peak heart rate was greater by ca 50 beats per min. Similar administration of vehicle failed to alter either parameter. Arterial pressure and heart rate in substance P-treated rats were significantly different from those in vehicle-treated rats up to 15–20 min after administration. Pretreatment with the sympathetic ganglion blocker, hexamethonium (10 mg/kg, i.v.), prevented the responses to intrathecal administration of substance P. Pretreatment with [ d-Pro 2, d-Phe 7, d-Trp 9]-substance P, an analogue with antagonist properties in the central nervous system, blocked both responses to substance P but failed to alter similar responses provoked by intrathecal administration of angiotensin II. Pretreatment with vehicle had no effect on responses to substance P or to angiotensin II. The antagonist also had partial agonistic effects. Both arterial pressure and heart rate were transiently increased, but this effect was reversed within 6 min; in the case of heart rate, values returned to the pre-application level but arterial pressure fell to ca 15 mm Hg below this level. These results demonstrate a pharmacologically specific excitatory effect of substance P on spinal mechanisms controlling sympathetic output to the vessels and the heart; this output can be either via the adrenal medullae or via nerve pathways to the vessels and the heart. Our results also support the possibility that dysfunction of substance P systems at the spinal level may underly some models of hypertension and may be involved in some cases of essential hypertension in man, as well as in autonomic dysfunction associated with some neurological disorders.