Age-related hypotensive effect of atropine in unanesthetized spontaneously hypertensive rats

Intravenous injection of atropine (0.5-20 mg/kg) produced a dose- and age-dependent decrease in the mean arterial pressure (MAP) of conscious spontaneously hypertensive (SH) rats 11-20 weeks of age. No effect on blood pressure occurred in age-matched Wistar-Kyoto (WKY) controls; however, heart rate was increased in both groups. In contrast to atropine, the same doses of methylatropine increased MAP and heart rate in both SH and WKY rats. Methylatropine also failed to modify the hypotensive effect of atropine in SH rats. The difference between the effects on blood pressure of atropine and methylatropine in SH rats was not seen when the animals were anesthetized with pentobarbital. In this case both agents reduced MAP. Intracerebroventricular (i.c.v.) injection of atropine in doses up to 200 microgram in SH rats failed to modify MAP and was without effect on the hypotensive response to intravenous injection of atropine. Likewise, i.c.v. injection of hemicholinium-3 (which reduces MAP in SH rats) failed to modify the hypotensive effect of atropine. However, intravenous injection of atropine (10 mg/kg) prevented the hypotensive effect of hemicholinium-3. Thee results are discussed in terms of central and peripheral muscarinic mechanisms.