Studies on the Cardiovascular Effects Produced by the Spinal Action of Substance P in the Rat

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Abstract
Administration of 6.5-pmol-6.5-nmol doses of substance P (SP) into the spinal subarachnoid space at T-8-T-10 in urethane-anesthetized rats increases both mean arterial pressure (MAP) and heart rate (HR) in a dose-related manner. However, in rats anesthetized with sodium pentobarbital, an increase in MAP is seen only at low doses of SP (6.5.sbd.65 pmol), while a biphasic response is obtained at 650 pmol and only a depressor response at 6.5 nmol SP. These responses also are accompanied by a tachycardia. Depending on the spinal cord level, cardiovascular responses of different time course and magnitude are elicited by SP. The amplitude of the increases in MAP and HR produced by SP (6.5 nmol) are: T-8.sbd.T-10 > T-1.sbd.T-3 > L-2.sbd.L-4 in rats anesthetized with urethane. In rats anesthetized with sodium pentobarbital, the decrease in MAP levels is greatest at T-1.sbd.T-3, while it is similar at T-8.sbd.T-10 and L-2.sbd.L-4 levels. The effects of SP on HR are more complex. The different cardiovascular responses obtained with the two anesthetics are not attributed to the relative depth of anesthesia but may be due to differential effects of the anesthetics on sympathetic nervous activity. The effect of SP on HR can be blocked by propranolol, but it remains unaffected by the surgical removal of the adrenal glands. We conclude that this cardiovascular response is most likely mediated by the postganglionic noradrenergic fibres and that adrenal medullary catecholamines are not essential. Using several inhibitors of endogenous mediators, two components to the spinal action of SP on MAP are made evident. The pressor response can be explained solely by the activation of sympathetic preganglionic fibres in the intermediolateral nucleus of the spinal cord, while the depressor response, in addition, may inolve the release of a vasodilatory substance in the periphery, the action of which persists in the presence of cholinergic, histaminergic, serotonergic, or opioid antagonists. Moreover, the adrenal glands are excluded as a possible source of this substance.