Age-dependent baroreflex attenuation by centrally infused verapamil in rats

DL Barringer and RD Bunag

Department of Pharmacology, College of Health Sciences and Hospital, University of Kansas Medical Center, Kansas City.

Because oral administration of verapamil for 6 days reduces reflex tachycardia without affecting reflex bradycardia, we tested chronotropic baroreflexes in conscious rats aged 5 or 15 months before and after verapamil was infused intracerebroventricularly for 6 days to determine whether a central action contributes to the reflex attenuation. Baroreflex responses consisted of reflex bradycardia elicited during pressor responses to methoxamine and reflex tachycardia during depressor responses to sodium nitroprusside. As we have shown previously, all reflex heart rate responses were initially smaller in 15-month-old than in 5-month old rats. Osmotic minipumps filled with saline or verapamil (100 micrograms/kg/day) were connected to cannulas in a lateral ventricle or femoral vein and, after 6 days, baroreflexes were recorded again. Control infusions of either saline intracerebroventricularly or verapamil intravenously were ineffective. In contrast, intracerebroventricular infusions of verapamil attenuated reflex heart rate responses to methoxamine or sodium nitroprusside differently in the two age groups: both reflex tachycardia and bradycardia were attenuated in 5-month-old rats; however, in 15-month- old rats only reflex bradycardia was reduced, whereas reflex tachycardia was unaffected. The selective reduction of reflex tachycardia in 5-month-old, but not in 15-month-old, rats suggests that intracerebroventricularly infused verapamil affects central baroreflex regulation differently depending on age.

Volume 253, Issue 1, pp. 158-164, 04/01/1990
Copyright © 1990 by American Society for Pharmacology and Experimental Therapeutics