Modulation of cardiovascular depressant action of clonidine by pentobarbital anesthesia in rats.

Abstract

The influence of pentobarbital anesthesia (5 mg 100 g, i.p.) on the cardiovascular depressor effect of clonidine administered intracerebroventricularly (i.c.v.) and intravenously (i.v.) was examined in rats. In conscious rats the hypotensive potency of i.v. clonidine [effective dose of clonidine which induced a decrease in blood pressure of 15 mmHg ; ED15 = 7 (pg/kg)] is greater than that of i.c.v. clonidine (ED15 =24.3), while in anesthetized rats that of icy. clonidine (ED15 -0.7 pg/kg) was greater than that of i.v. clonidine (ED15 = 3.5 p g/kg). Pentobarbital anesthesia potentiated the hypotensive potency of i.c.v. clonidine in conscious rats by 50 times, while it potentiated that of i.v. clonidine only by 2 times. The bradycardic potency of i.v. and i.c.v, clonidine was also potentiated by pentobarbital anesthesia. These pieces of evidence suggest that in conscious rat, the hypotensive action of i.c.v. clonidine is opposed by a centrally mediated hypertensive effect of the drug and that pentobarbital anesthesia suppresses the clonidine sensitive pressor center and so potentiates the hypotensive effect of i.c.v. clonidine blood pressure; cerebroventricular injection ; clonidine ; heart rate ; pentobarbital There is a volume of evidence to indicate that the hypotensive and bradycardic effects of clonidine are mediated by a2-adrenoceptor and/or imidazole receptor mechanisms in the depressor site of the medullary vasomotor center (Schmitt 1977;Kobinger 1978;Ernsberger et al. 1987). Studies which have shown that centrally administered clonidine caused greater hypotensive effects than the same dose given intravenously (Kobinger 1978) have been a part of that evidence which indicates a central mode of action. Such results have been obtained in several species of animal mainly under anesthetized conditions. However, there is no report of a significant difference in the hypotensive potency of clonidine via different administration route in rats, the most pupular experimental animal. We

The Dual Cardiovascular Effect of Centrally Administered Clonidine: A Comparative Study between Pentobarbital- and Ketamine/Xylazine-Anesthetized Rats

“…On the other hand, clonidine evoked pressor responses and bradycardia when administered into the central nervous system of ketamine/xylazine-anesthetized rats, reproducing data obtained in studies using conscious normotensive rats [24]. It was previously demonstrated that the hypotensive effect of both i.v.- [37] and i.c.v.-administered [21] clonidine was significantly potentiated by pentobarbital anesthesia in rats, circumventing the previously mentioned vasoconstrictor effect of clonidine. Clonidine has been administered as premedication or during anesthesia in humans, and its use has been associated with multiple benefits, including reduced anesthetic requirement [38] and improved hemodynamic parameters [39].…”

“…Although multiple studies have reproduced the antihypertensive effect of clonidine, a closed analysis of the literature reveals that such findings are strikingly dependent on experimental conditions. The administration of clonidine using the intracerebral route decreased the blood pressure of both conscious hypertensive [17] and anesthetized animals [18][19][20][21][22]. However, despite its efficacy against hypertension, the i.c.v.…”