Centrally Mediated Cardiovascular Effects of Intracisternal Application of Carbachol in Anesthetized Rats

Abstract

Abstract-The pressor response to the intracisternal (i.e.) injection of carbachol (1 µg) in anesthetized rats was analyzed. This response was significantly reduced by the intravenous (i.v.) injection of guanethidine (5 mg), hexamethonium (10 mg) or phen tolamine (5 mg), and conversely, potentiated by i.v. desmethylimipramine (0.3 mg), while propranolol (0.5 mg) i.v. selectively inhibited the enlargement of pulse pressure and the tachycardia following i.e. carbachol (I ug). On the other hand, the pressor response to i.e. carbachol (1 ,g) was almost completely blocked by i.e. atropine (3 µg) or hexamethonium (500 µg), and significantly reduced by i.e. chlorpromazine (50 lag) but significantly potentiated by i.e. desmethylimipramine (30 µg). The pressor response to i.e. carbachol (I yg) remained unchanged after sectioning of the bilateral cervical vagal nerves but disappeared after sectioning of the spinal cord (C7-C8). From the above result it is suggested that the pressor response to i.e. carbachol originates in the central muscarinic mechanism, is exerted through the central and peripheral adren ergic mechanisms, and that the sympathetic trunk is the main pathway.

Cholinomimetic and anticholinergic drugs used to investigate an acetylcholine hypothesis of affective disorders and stress

“…Supportive of this possibility, sympathetic efferent neuronal activity has been shown to be enhanced following central muscarinic stimulation [Kaul and Grewal, 1968;Varagic and Vojvadic, 19571, and administration of drugs which enhance peripheral sympathetic activity enhance the pressor response to cholinomimetics [Ozawa and Uematsu, 1976;Lesic and Varagic, 1961;Varagic, 19551. Also, the stress-sensitive adrenal hormones, epinephrine and norepinephrine, are consistently released following administration of centrally acting cholinomimetics, effects blocked by centrally acting anticholinergic agents [Stamenovic and Varagic, 1970;Cass and Spriggs, 1961;Schmitt and Fenard, 1972;Brezenoff, 19731. Conversely, studies have shown that drugs that block the peripheral sympathetic nervous system cause significant attenuation of cholinomimetic-induced pressor responses.…”

Modulation of the pressor response elicited by carbachol and electrical stimulation of the amygdala by muscarinic antagonists in conscious rats

“…Centrally acting cholinoceptor agonists and cholinesterase inhibitors are known to induce pressor (Varagic, 1955; Dirnhuber & Cullumbine, 1955; Krstic & Djurkovic, 1973; Ozawa & Uematsu, 1976; Buccafusco & Brezenoff, 1979; Brezenoff & Giuliano, 1982; Oktay et al , 1984; Sundaram et al , 1988; özkutlu et al , 1993) and depressor responses (De Wildt & Porsius, 1981; Criscione et al , 1983; Murugian et al , 1989; Sundaram et al , 1989; Hara et al , 1992; Ally et al , 1993) associated with a tachycardia or a bradycardia depending on species and mode of administration. In rats, activation of central muscarinic receptors results primarily in hypertension (see Buccafusco, 1996).…”