Neural mediation of the cardiovascular responses to intrathecal administration of substance P in the rat: slowing of the cardioacceleration by an adrenal opioid factor.

Substance P, given intrathecally at the second (T2) or ninth (T9) thoracic level in the anesthetized rat, increased heart rate, arterial pressure and circulating catecholamines. At T9 in adrenalectomized animals and at T2 in intact animals, the cardioacceleration was more abrupt than in intact animals injected at T9 suggesting that the adrenals are not necessary for the cardiovascular responses and that the adrenals may have released a factor which slows the neurally mediated cardioacceleration. As opioids are co-released with catecholamines from the adrenals, naloxone (10 mg/kg i.v.) or nalorphine HCl (which does not cross the blood-brain barrier; 10 mg/kg s.c.) was given 5 min before administration of substance P at T9 in intact rats. In both groups the cardioacceleration was similar to that elicited in adrenalectomized animals, indicating that the adrenal factor was opioid and that its action was peripheral rather than central. When propranolol (10 mg/kg i.v.) was given 3 or 15 min before, substance P increased arterial pressure but heart rate was unchanged, indicating that the opioid factor was not slowing the cardioacceleration by a direct effect on the heart. The results indicate that intrathecal administration of substance P produces a neurally mediated increase in arterial pressure and heart rate and induces the release of an adrenal opioid factor which slows the neurally-mediated cardioacceleration by an action in the periphery. This indicates a functional interaction between humoral and neural sympathetic mechanisms regulating the cardiovascular system.