Ketanserin versus urapidil: age-related cardiovascular effects in conscious rats

To examine whether serotonin (5-hydroxtryptamine, 5-HT)-mediated mechanisms for regulating blood pressure are influenced by advancing age, the cardiovascular effects of ketanserin and urapidil were compared in two groups of conscious rats at ages 4 (young) and 24 (old) months. Old rats had higher mean pressures but the same basal heart rates as young rats prior to drug treatment. Subsequent treatment with either ketanserin or urapidil produced similar cardiovascular effects. Both drugs in doses of 10 mg/kg i.v., lowered mean pressures more markedly in old than in young rats, and the larger hypotensive response in old rats was statistically significant even when expressed as percent reductions. Because drug treatment abolished the mild hypertension initially present in old rats, ensuing blood pressure levels no longer differed between age groups. On the other hand, neither drug had any appreciable effects on basal heart rate or angiotensin-induced reflex bradycardia at any age. Consequently, hypotensive enhancement in old rats cannot be due to age-related changes in reflex bradycardia. Inasmuch as ketanserin and urapidil, despite their differing modes of action on 5-HT receptors, were both equally adept at lowering blood pressure more in old rats, these results suggest that enhancement occurs selectively only with 5-HT-mediated hypotension. Thus, unlike other antihypertensive drugs (like prazosin or lisinopril) whose modes of action do not include 5-HT mediation and whose hypotensive effects do not increase with age, our results suggest that hypotensive responses to ketanserin and urapidil are selectively enhanced because of their actions on 5-HT receptors.