Antiproliferative effects of the serotonin type 2 receptor antagonist, ketanserin, on smooth muscle cell growth in rats.

We defined the role of a serotonin type 2 receptor antagonist, ketanserin, in the growth of aortic vascular smooth muscle cells (VSMCs) from Wistar rats, using cell culture and cell synchrony methods. Deoxyribonucleic acid (DNA) replication in the G0/G1- or G1/S-synchronized VSMCs was assessed by [3H]thymidine uptake into DNA. Ketanserin at 2 x 10(-5) M significantly decreased the thymidine uptake by 48% in the proliferating VSMCs, whereas methysergide, a nonspecific serotonin inhibitor, unaffected the thymidine uptake. Ketanserin at 10(-5) M did not influence the duration of the G1 resting period. However, this dose of ketanserin significantly lowered DNA replication in the DNA synthetic (S) period in a dose-dependent manner. Neither methysergide nor the alpha 1-adrenoceptor antagonist, prazosin, affected DNA synthesis in the S period. Ketanserin exhibits antiproliferative effects on rat VSMC growth probably through the suppression of DNA replication in the S phase. This property would also contribute to the vascular protective effects of ketanserin with its well-documented antihypertensive action.