5-CARBOXAMIDOTRYPTAMINE ATTENUATES THE DEVELOPMENT OF DEOXYCORTICOSTERONE ACETATE-SALT HYPERTENSION IN RATS

The effect of chronic i.v. infusion of the 5-HT1 receptor agonist, 5-carboxamidotryptamine (5-CT), was evaluated during the development of deoxycorticosterone acetate-salt (DOCA-salt) hypertension in rats over 4 weeks. Vehicle-treated (n = 10) Sprague-Dawley rats given DOCA (100 mg/kg, s.c.) and 1% saline as drinking fluid developed hypertension with systolic blood pressure reaching 194.6 +/- 8.99 mm Hg at 27 days. In DOCA-salt rats treated with 5-CT infusions (15.0 mu g/kg per day, n = 10) for 4 weeks via osmotic minipumps, systolic blood pressure was significantly lower by 41.7 mm Hg at day 27 when compared to vehicle-treated DOCA-salt rats. Systolic blood pressure values on day 27 in 5-CT-treated DOCA-salt rats were however greater than those in vehicle-treated control rats which were not given DOCA. Systolic blood pressure in 5-CT-treated DOCA-salt rats was significantly lower by day 7 compared to vehicle-treated DOCA-salt rats and remained lowered for the rest of the observation period. Heart rate was significantly greater in 5-CT-treated DOCA-salt rats on day 7 when compared to vehicle-treated DOCA-salt rats. Baroreflex sensitivity on day 28 was significantly greater in 5-CT-treated DOCA-salt rats as compared to vehicle-treated DOCA-salt rats. On day 28, hypotensive responses to hexamethonium (20 mg/kg) in 5-CT-treated DOCA-salt rats were markedly reduced compared to those in vehicle-treated DOCA-salt rats. The data suggest that chronic administration of 5-CT attenuates the development of DOCA-salt hypertension in rats with concomitant attenuation of the dampening of baroreflex sensitivity seen during the development of hypertension. The results also suggest a peripheral sympathoinhibitory action of 5-CT in addition to the known peripheral vasodilatation via 5-HT1 receptors.