Spinal muscarinic, glutamatergic and GABAergic receptor systems in cardiovascular regulation.
The central administration of cholinergic agonists can produce a significant increase in arterial blood pressure by enhancing sympathetic vasomotor tone. The stimulation of spinal muscarinic receptors through intrathecal (i.t.) injection of carbachol in rats evoked a significant pressor response that returned to preinjection levels within 30 to 40 min. We investigated the roles of glutamatergic and GABAergic receptors in mediating the hypertensive response to i.t. injection of the muscarinic receptor agonist carbachol and in the maintenance of resting blood pressure and heart rate. The i.t. pretreatment with the N-methyl-D-aspartate (NMDA) receptor antagonists D-AP7 or MK801 maleate (dizocilipine) attenuated the pressor response to i.t. administration carbachol in a dose-dependent manner in conscious, freely moving rats. In contrast, i.t. pretreatment with 6-cyano-7-nitroquinoxaline-2,3-dione, a non-NMDA glutamate receptor antagonist, was not effective in this regard, indicating that the carbachol-evoked pressor response was not mediated through the quisqualate/kainate subtype of glutamate receptors. The i.t. pretreatment with the gamma-aminobutyric acid type B receptor agonist baclofen also inhibited the pressor response to i.t. injection of carbachol at doses that did not alter motor function. To determine whether the pressor response to stimulation of spinal muscarinic receptors required the participation of higher centers, rats received an intracisternal injection of either methylatropine or D-AP7 before the i.t. injection of carbachol. Both intracisternal pretreatments significantly reduced the expression of the pressor response to i.t. injection of carbachol. These findings are consistent with the presence of a powerful modulating spinobulbar muscarinic pressor system. Pharmacological activation of this system involves the participation of spinal and perhaps medullary glutamate-NMDA and gamma-aminobutyric acid type B receptor systems.
Feldman
D S
DS
Department of Pharmacology and Toxicology and Alzheimer's Research Center Medical College of Georgia, Augusta 30912-2300, USA.
Buccafusco
J J
JJ
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001418:Baclofen / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D002217:Carbachol / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018079:Receptors, GABA / Q000502:physiology*; D017470:Receptors, Glutamate / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*
D018079:Receptors, GABA; D017470:Receptors, Glutamate; D011976:Receptors, Muscarinic; D016291:Dizocilpine Maleate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D001285:Atropine; D002217:Carbachol; D001418:Baclofen; C031231:2-amino-7-phosphonoheptanoic acid