Cardiovascular and muscle tone changes produced by microinjection of cholinergic and glutamatergic agonists in dorsolateral pons and medial medulla

Abstract

Cardiovascular and muscle responses to L-glutamic acid (Glut) and cholinergic agonists injected into the dorsolateral pontine tegmentum and medial medullary reticular formation (MMRF) were examined in unanesthetized, decerebrated cats. Glut, or cholinergic agonists acetylcholine (ACh) or carbachol (Carb), were injected into pons and MMRF at sites from which electrical stimulation produced bilateral suppression of muscle tone. Glut injection in MMRF produced hypotension without change in heart rate at doses as low as 1 mM. At higher doses (0.1-0.4 M), Glut induced hypotension with bradycardia in 23 out of 40 injections in both pons and MMRF. High concentrations of microinjected Glut decreased muscle tone or produced complete atonia in pons and rostral MMRF. Both N-methyl-D-aspartic acid (NMDA) and non-NMDA receptor blockers attenuated or completely blocked the cardiovascular response, while only non-NMDA antagonists blocked muscle inhibition to Glut injection. Microinjection of cholinergic agonists produced consistent hypotension in all of the injections in pons and MMRF, however, the heart rate response was variable with increase (27/42), decrease (2/42), or no change (13/42) in rate seen. Cholinergic injection produced muscle atonia in pons and caudal MMRF but not in rostral MMRF. Both muscle and cardiovascular responses were blocked by atropine but not by hexamethonium. The time course of muscle atonia and cardiovascular change differed in most of the experiments. We conclude that muscle tone suppression and cardiovascular response to Glut or cholinergic agonists use different receptor mechanisms and possibly different neurons. However, the co-localization of these mechanisms suggests that neuronal networks in the medial medulla and dorsolateral pons coordinate motor and cardiovascular responses.

Fig. 1.

Sites of L-glutamic acid (Glut) injection in the pons (P2‒P4) and medulla (P8‒P14). 0.2 M/0.5 μl of Glut injection in the brainstem produced either cardiovascular change (≥5%) or no effect (<5%). The symbols in the left and right side represent cardiac and blood pressure responses to Glut, respectively. The open and closed symbols represent increase and decrease of cardiovascular variables, respectively. For details see text. •: <5%, ●,○: ≥5%; ★,☆: ≥15%; ▲,△: ≥25%; ◼,◻: ≥35%; ◆,◇: ≥45%; 4V: fourth ventricle; 7: facial nucleus; BC: brachium conjunctivum; CNF: nucleus cuneiformis; IC: nucleus inferior colliculus; IO: inferior olive; LC: nucleus locus coeruleus; MLB: medial longitudinal bundle; NGC: nucleus gigantocellularis; NMC: nucleus magnocellularis; NPM: nucleus paramedianus; PT: pyramidal tract; SO: superior olive.

Fig. 2.

Glut (0.2 M/O.5 μl) injection into rostral dorsolateral medulla produced hypertension with bradycardia. The latency of cardiovascular response to Glut is short (8 s). Facilitation of muscle tone was also found after the injection. The dot in the left figure represents the injection site. A: cardiovascular and muscle responses to Glut injection; B: cardiovascular and muscle changes return to baseline after the injection (B is 12 min after A). BP: blood pressure; Glut: L-glutamic acid; LOS: left occipitoscapularis; LS: left splenius; LBC: left biventer cervicis; ROS: right occipitoscapularis; RS: right scapularis; RBC: right biventer cervicis; LTB, left triceps brachii; RTB, right triceps brachii.

Fig. 3.

Dose-dependent blood pressure response to ACh injection in the medulla. Four experiments were done at each concentration. 0.5 μl ACh solution at each dose was injected into rostro-ventral medulla (NMC). The magnitude of the control baseline was the average of 6 sample points at 30 s interval during the 3 min recording prior to the first injection.

Fig. 4.

Sites of cholinergic agonist injections in the brainstem. The symbols in the left and right side represent cardiac and blood pressure responses to cholinergic injection, respectively. Carbachol was injected in pons only and produced prolonged hypotension with no change of heart rate. ACh injection produced hypotension with variable change of heart rate in most of the experiments. Tachycardia was always found in the pons and the rostral medulla, while tachycardia, bradycardia, or no change were seen in the caudal medulla. See Fig. 1 for the symbols and abbreviations.

Fig. 5.

Simultaneous change of blood pressure and muscle activity induced by Glut injection in the rostral medulla (NMC).

Fig. 6.

Cardiovascular and muscle responses to Glut and ACh injection in NMC. Glut injection produced muscle atonia without change of blood pressure and heart rate. However, ACh injection produced decreased blood pressure and increased heart rate, but no change in muscle activity. Saline vehicle injection did not produce either cardiovascular or muscle change. Note change in paper speed and difference in EMG gain in ACh injection.