Microinjection of substance P and ACh into rat intermediolateral nucleus elicits cardiovascular responses.
ABSTRACT The effects of substance P (SP) or acetylcholine (ACh) microinjected into the intermediolateral nucleus of the spinal cord (IMLn) on arterial pressure (AP) and heart rate (HR) were investigated in 22 male Wistar rats under urethan and artificial ventilation. L-Glutamate (Glu) was microinjected into the IMLn between C7 and T4 to locate cardiovascular sites. Micropipettes containing Glu were stereotaxically positioned in 82 histologically verified sites in the IMLn between C7 and T4 on both the right and left sides. Microinjection of 4-10 nl of 0.18 M Glu in 30 of 39 explored sites at the T2 level elicited significant increases in HR (+24.2 +/- 3.1 beats/min). These changes were accompanied by significant increases in mean AP (+11.4 +/- 1.2 mmHg) at the T2 level (32/47 sites). Microinjection of 4-10 nl of SP (3 X 10(-7) to 3 X 10(-4) M) or ACh (0.005-0.5 M) in the right IMLn at the T2 level elicited increases in HR but did not affect AP. The duration of the responses to SP or ACh was significantly longer than the duration of the responses to Glu. The responses to ACh could be blocked by prior microinjection of 5 X 10(-2) M atropine. No responses were ever obtained in the left IMLn by microinjection of Glu, SP, or ACh. These results support the hypothesis that Glu, ACh, and SP mediate sympathoexcitation in the IMLn of the rat and that these excitatory responses have different temporal patterns.
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ABSTRACT: 1. We have used microinjections of glutamate, an ionotropic excitatory amino acid receptor antagonist (kynurenate) and selective ionotropic (NMDA and kainate) and metabotropic (1S-3R-ACPD, trans-ACPD and L-AP4) receptor agonists in the thoracic IML of the rat to define the receptors mediating the tachycardia produced by excitatory amino acid antagonists. 2. Injection of glutamate (delta heart rate = 76 +/- 8 beats/min n = 16), NMDA (delta heart rate = 116.5 +/- 5 beats/min n = 6) or kainate (delta heart rate = 92 +/- 22 beats/min n =6 evokes a tachycardia when injected into the thoracic intermediolateral column. Kynurenate blocked the response to NMDA (-2% of initial response) and markedly attenuated the response to kainate (14% of initial response) but did not alter the response to glutamate (106% of initial response). 3. IS-3R-ACPD did not elicit a tachycardia when injected into the thoracic intermediolateral column and neither trans-ACPD nor L-AP4 induced a tachycardia after kynurenate injection into the thoracic intermediolateral column. 4. Thus stimulation of either NMDA or AMPA/kainate receptors elicits tachycardia in rat thoracic spinal cord but glutamate also activates another receptor type to elicit a tachycardia. The lack of a tachycardia when trans-ACPD, 1S-3R-ACPD or L-AP4 were injected into the thoracic spinal cord suggests that the kynurenate resistant tachycardia elicited by glutamate is not mediated by metabotropic receptors. The kynurenate resistant tachycardia elicited by glutamate is not mediated by any of the known excitatory amino acid receptor types.Clinical and Experimental Pharmacology and Physiology 10/1996; 23(9):813-8. · 2.16 Impact Factor
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ABSTRACT: The aim of this study was to determine which of the muscarinic receptor subtypes are involved in the modulation of the urethrogenital reflex (UGR) in male, spinal cord-transected rats. The electromyographic (EMG) responses of the bulbospongiosus muscle (BS) to the topical spinal application of muscarine and the combination of muscarine and the selective muscarine receptor antagonists methoctramine (M2), AFDX (M2), 4DAMP (M3) and tropicamide (M4) were determined before and after the elicitation of UGR by way of the mechanical stimulation of the urethra. When 50- and 100-mug doses of muscarine were applied without urethral stimulation, a rhythmic activity of the BS was observed, similar to the one found when UGR was evoked. The M3 and M4 - but not the M2 - antagonists prevented BS response to muscarine when urethral stimulation was not performed. When UGR was elicited following urethral stimulation muscarine produced an increase in burst duration and a decrease in burst frequency. The M2 antagonist reverted the effects of muscarine on the UGR, while the M3 and M4 antagonists produced a significant increase in the frequency and in the bursts number, when compared to the control muscarine response. The differences observed in BS responses to muscarine and muscarine antagonists before and after UGR elicitation were probably linked to the intrinsic effects of the endogenous acethylcholine (Ach) released after urethral stimulation. The present results suggest a cholinergic modulation of UGR in spinal cord-transected rats mediated by the M2, M3 and M4 muscarinic receptor subtypes.Pharmacology Biochemistry and Behavior 06/2005; 81(1):100-13. · 2.61 Impact Factor