RT Journal Article
SR Electronic
T1 Studies on the hypotensive response to atropine in hypertensive rats.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 662
OP 668
VO 218
IS 3
A1 S Abraham
A1 E H Cantor
A1 S Spector
YR 1981
UL http://jpet.aspetjournals.org/content/218/3/662.abstract
AB The hypotensive effect of atropine sulfate was evaluated in conscious, unanesthetized hypertensive rats (spontaneously hypertensive rats and Sprague-Dawley rats made hypertensive by s.c. implantation of deoxycorticosterone acetate, tablets) and their respective normotensive controls. In all animals, atropine (5-50 mg/kg i.v.) caused an immediate and dose-dependent decrease in blood pressure. However, the hypotensive response was of greater magnitude and of longer duration in the hypertensive rats. Pretreatment of the animals with phentolamine prevented the hypotension by atropine. Plasma concentrations of atropine were determined by radioimmunoassay and were identical in both hypertensive and normotensive rats. Atropine blocked the pressor responses to norepinephrine and shifted the dose-response curve for norepinephrine to the right to a similar extent in spontaneously hypertensive and Wistar-Kyoto rats. Thus, atropine acts as a competitive antagonist of norepinephrine and this action underlies its hypotensive effect. The greater responsiveness of hypertensive rats is not due to a difference in pharmacokinetic handling of atropine nor to a greater degree of blockade of the norepinephrine pressor response in vivo, but may result from the altered sympathetic tone in the hypertensive rats. Atropine may, in addition to its action on alpha adrenergic receptors, affect other systems such as calcium handling. It is speculated that an effect on this system may contribute to the longer duration of response seen in hypertensive rats.