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

Abstract

SUMMARY Kainic acid (KA), an analogue of L-glutamate, was microinjected in 0.1 pi of saline into the nucleus tractus solitarii (NTS) of adult rats. In rats anesthetized with halothane or a-chloralose, KA injected unilaterally elicited hypotension, bradycardia, and apnea. The threshold dose was 0.1-0.2 ng (10~1 3 mol). Doses >0.2 ng blocked responses to subsequent injections for at least 30 minutes. Doses of KA >15 ng reduced the reflex bradycardia elicited by raising the arterial pressure with phenylephrine and produced arterial hypertension in rats anesthetized with a-chloralose or in other rats within 15 minutes of terminating halothane anesthesia. Bilateral injection of KA in doses >15 ng completely blocked baroreflexes and resulted in a dose-dependent elevation of arterial pressure (167 ± 9.4; P < 0.001) both in a-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 cadiovascular 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. Circ Res 48: 292-298, 1981 ANATOMICAL and electrophysiological studies have established that the intermediate one-third of the nucleus tractus solitarii (NTS) is the principal site of termination of the primary afferent fibers of baroreceptor nerves (Crill and Reis, 1968;Miura and Reis, 1969;Seller and Illert, 1969;Jordan and Spyer, 1977). Electrical stimulation restricted to this area simulates baroreflexes by eliciting hypotension and bradycardia (Crill and Reis, 1968;DeJong et al., 1975). On the other hand, restricted electrolytic lesions abolish baroreflexes and, in unanesthetized animals, result in neurogenic hypertension. In the rat the hypertension is fulminating (Doba and Reis, 1973;DeJong and Palkovits, 1976) whereas in the cat (Nathan and Reis, 1977) or dog (Carey et al., 1979;Schmitt and Laubie, 1979) it is chronic and labile. It is uncertain whether the hypertension produced by electrolytic lesions of NTS is a consequence of destruction of intrinsic neurons of the NTS or of interruption of the primary afferent baroreceptor fibers terminating in or passing

Cardiac damage after lesions of the nucleus tractus solitarii

“…Specifically, we do not contend that the cardiac events reported here were directly and specifically related to an effect on the NK1 receptor itself. However, the advantage of using the toxin for that receptor over other means of interrupting the baroreflex at the level of NTS is that baroreflex interruption occurred more slowly with the toxin and allowed the animals to survive without manifesting signs of extreme neurogenic hypertension and pulmonary edema associated with early death as occurs after placement of an acute destructive lesion (5,31).…”

IL-6 microinjected in the nucleus tractus solitarii attenuates cardiac baroreceptor reflex function in rats

“…This is highly suggestive that the NTS is a central brain stem structure that plays a vital role in maintaining the set point of arterial pressure. Equally, because baroreceptor afferents terminate in this nucleus (4), it is also one of the most effective central sites for modulating baroreceptor reflex function, a process that is critically important for blood pressure homeostasis (9,18,21,26). Based on this evidence, we hypothesized that abnormal function of the NTS contributes to the development of neurogenic hypertension through effects on both set-point and baroreceptors reflex function (33).…”

Junctional Adhesion Molecule-1 Is Upregulated in Spontaneously Hypertensive Rats

“…Although numerous brain stem regions can control sympathetic nerve activity, the nucleus of the solitary tract (NTS) is one of the key central regions playing a role in the regulation of both the set point of arterial pressure, 9 -11 as well as baroreflex gain control, a feedback mechanism essential for homeostatic regulation of arterial pressure. 10,12,13 A preliminary cDNA microarray experiment 14 suggested several differentially expressed genes in the NTS between SHR and their progenitor strain, the WKY rat. One of them 17 This might be important, because leukocyte accumulation within the systemic circulation was deemed to be a contributing factor for the hypertension in the SHR because of enhanced hemodynamic resistance.…”