Acute hypertension after the local injection of kainic acid into the nucleus tractus solitarii of rats.

Abstract

Kainic acid (KA), an analogue of L-glutamate, was microinjected in 0.1 microliter of saline into the nucleus tractus solitarii (NTS) of adult rats. In rats anesthetized with halothane or alpha-chloralose, KA injected unilaterally elicited hypotension, bradycardia, and apnea. The threshold dose was 0.1-0.2 ng (10(-13) mol). Doses greater than 0.2 ng blocked responses to subsequent injections for at least 30 minutes. Doses of KA greater than 15 ng reduced the reflex bradycardia elicited by raising the arterial pressure with phenylephrine and produced arterial hypertension in rats anesthetized with alpha-chloralose or in other rats within 15 minutes of terminating halothane anesthesia. Bilateral injection of KA in doses greater than 15 ng completely blocked baroreflexes and resulted in a dose-dependent elevation of arterial pressure (167 +/- 9.4; P less than 0.001) both in alpha-chloralose-anesthetized rats and in awake rats after the termination of halothane anesthesia. The hypertension rapidly led to pulmonary edema and death. Procaine microinjected also elicited fulminating hypertension; vehicle did not. Doses of KA producing hypertension caused no histological or biochemical evidence of neuronal death. The cardiovascular responses to KA were restricted to sites in the intermediate one-third of NTS and could not be elicited by injection into adjacent sites in brainstem. The results indicate that, in low doses, KA injected into NTS stimulates neurons which mediate the baroreflex, whereas, in higher doses, it produces baroreflex blockade and neurogenic hypertension. The results suggest that fulminating hypertension can be produced by nondestructive perturbations of neurochemical transmission in brain. Since the cardiovascular responses of KA are similar to those produced by microinjection into NTS of the amino acid neurotransmitter glutamic acid, the study adds further support to the hypothesis that L-glutamate is the neurotransmitter released by baroreceptor afferent nerves.