Does chronic ketanserin treatment enhance bradycardia in old rats by serotonergic blockade?

• Published in: Aging (Milan, Italy) Italy), 1998-04, Vol.10 (2), p.102-111
• Main Authors: Buñag, R D, Davidow, L W
• Format: Article
• Language: English
• Subjects: Adrenergic alpha-Agonists - pharmacology; Age; Aging - physiology; Animals; Antihypertensive Agents - administration & dosage; Antihypertensive Agents - toxicity; Blood Pressure - drug effects; Body Weight; Bradycardia - chemically induced; Cardiac arrhythmia; Heart Rate - drug effects; Ketanserin - administration & dosage; Ketanserin - toxicity; Male; Phenylephrine - pharmacology; Rats; Rats, Sprague-Dawley; Rodents; Serotonin - pharmacology; Serotonin Antagonists - administration & dosage; Serotonin Antagonists - toxicity; Tachycardia - chemically induced
• ISSN: 0394-9532; 1594-0667; 1720-8319
• DOI: 10.1007/BF03339644

To determine if the cardiovascular effects of chronic treatment with ketanserin would vary with increasing age, ketanserin was given by daily gavage for 14 days to male Sprague-Dawley rats at ages 4, 14, or 24 months. Before treatment, 24-month-old rats had higher blood pressures and weaker reflex heart rate responses than younger rats. Treatment with ketanserin caused hypotension, enhanced bradycardia, attenuated reflex tachycardia, and reversed serotonin (5-HT) responses, with all effects being more pronounced in 24-month-old rats than in younger rats. None of the age-related effects can be attributed to alpha-adrenergic blockade because they occurred even while cardiovascular responses to phenylephrine, an alpha 1-adrenergic agonist, were unaltered at any age. On the other hand, serotonergic blockade seems a more likely explanation because reversal or enhancement by ketanserin of cardiovascular responses to serotonin was age-related, being more marked in 14- and 24- than in 4-month-old rats. Our results suggest that as the cardiovascular effects of ketanserin become more pronounced with advancing age, 5-HT blockade intensifies and bradycardia becomes augmented until the ensuing cardiac inhibition eventually accentuates the hypotensive effects in older rats.