PT  - JOURNAL ARTICLE
AU  - K H Park
AU  - J P Long
AU  - J G Cannon
TI  - Evaluation of the central and peripheral components for induction of postural hypotension by guanethidine, clonidine, dopamine2 receptor agonists and 5-hydroxytryptamine1A receptor agonists.
DP  - 1991 Dec 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1221--1230
VI  - 259
IP  - 3
4099  - http://jpet.aspetjournals.org/content/259/3/1221.short
4100  - http://jpet.aspetjournals.org/content/259/3/1221.full
SO  - J Pharmacol Exp Ther1991 Dec 01; 259
AB  - Previously, it was observed that the severity of postural hypotension in rats after i.v. administration is: guanethidine (severe) greater than clonidine greater than dopamine2 (DA2) receptor agonists greater than 5-hydroxytryptamine1A (5-HT1A) receptor agonists (none). In this paper we investigated central and peripheral mechanisms involved in postural hypotension induced by these drugs. Intracerebroventricular or intracisternal doses of the above agents produced a fall in mean arterial pressure of 32 to 42 mm Hg and were used for evaluation of the central component. Intracerebroventricular, but not intracisternal, clonidine induced postural hypotension. DA2 or 5-HT1A receptor agonists did not induce postural hypotension after either i.c.v. or intracisternal administration. Intracerebroventricular guanethidine did not lower arterial pressure dose-dependently, or did it produce postural hypotension. A peripheral action postulated to be involved in the postural hypotension was inhibition of sympathetic neurotransmission; to evaluate this inhibition, drug effects on pressor and tachycardiac responses elicited by electrical stimulation in pithed rats were determined. Inhibition of heart rate changes by each of the drugs was: guanethidine, 60 to 100% at 0.1 to 8.0 Hz; clonidine, 20 to 40% at 0.1 to 2.0 Hz; DA2 receptor agonists, 10 to 45% at 0.1 to 2.0 Hz; and 5-HT1A receptor agonists, 20 to 40% at less than or equal to 0.5 Hz. These data indicate that the frequency selective inhibition in the peripheral sympathetic nervous system may explain the likelihood of postural hypotension for guanethidine, clonidine DA2 and 5-HT1A receptor agonists. Clonidine has some central component for induction of postural hypotension in addition to the frequency-related peripheral component.