Inhibition by topically applied clonidine and guanfacine on the pressor response to stimulation of the locus coeruleus in cats.

There is considerable evidence that a adrenergic mechanisms within medulla and hypothalamus play a role in cardiovascular regulation (1-4). Apart from the action on medullary mechanisms, clonidine has been reported to elicit hypotension by an action on hypothalamic a-adrenergic receptors and the possible mechanism of action of the drug applied into the hypothalamus has hitherto been discussed in relation to the descending pathways from the hypothalamus to the medullary cardiovascular control system (3, 5-8). Contrary to this, there has been no available report referring to an effect of clonidine on the ascending noradrenergic pathway from the locus coeruleus (LC) to the posterior hypothalamus (HPA), which is assumed to be involved in regulation of arterial blood pressure (9, 10). In addition, it is not clear whether clonidine acts either as an a-adrenergic agonist at the presynaptic receptor or as an a-adrenergic antagonist at the postsynaptic receptor (3, 11). Guanfacine, N-amidino-2-(2,6-dichloro phenyl) acetamide HCI, which resembles clonidine in chemical structure, appears to produce its hypotensive effects as a result of presynaptic a-adrenoceptor stimulation at central sympathetic control systems, though the possible site of central action of the drug has not yet been defined (12, 13). Thus, it was of interest to investigate an effect of clonidine and guanfacine injected into HPA on the pressor response to electrical stimu lation of the LC. Cats of either sex weighing 2.2-3.5 kg were anesthetized with a-chloralose-ure thane. After tracheotomy, the left carotid artery was catheterized for measurement of the blood pressure with a pressure transducer. A coaxial electrode was stereo taxically inserted into right or left LC (P2, L2, H-2) according to the atlas of Berman (14) for electrical stimulation with square wave pulses of 1 msec duration at 250 Hz, 3-5 V for 10 sec. Before the drug application, the LC was stimulated electrically three or four times every 10 min to elicit nearly a constant pressor response (a rise of the mean arterial blood pressure), and three pressor responses were averaged for the control. Then, a drug solution was injected into HPA (F 9.5, L 0.8, H-2.5) at a rate of 1 /d/30 sec with a microsyringe of 1 al introduced through the guide cannula which was cemented to the skull, and the LC was stimulated to evoke a pressor response 10, 30, 60 and 90 min after injection. The drug effect was estimated by comparing the pressor responses before and after injection …